This document discusses oxidative stress as a major cause of male infertility. It notes that reactive oxygen species (ROS) levels in semen can negatively impact sperm quality and function, potentially causing DNA damage. Antioxidants play an important role in protecting against oxidative stress. The document examines several antioxidants in detail, including superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It reviews evidence that oral supplementation with antioxidants may help treat male infertility associated with oxidative stress by reducing ROS levels and improving semen parameters and pregnancy rates. However, more research is still needed to determine the optimal antioxidant therapies.
This document summarizes the causes and consequences of oxidative stress in spermatozoa. It discusses how spermatozoa are vulnerable to oxidative attack due to their lack of antioxidant protection and high levels of polyunsaturated fatty acids. Oxidative stress can damage sperm membranes through lipid peroxidation, suppressing motility. It also causes DNA damage that is associated with miscarriage and developmental abnormalities. While reactive oxygen species are important for sperm capacitation, excessive levels can overwhelm antioxidant defenses and induce apoptosis. The main source of oxidative stress in spermatozoa is mitochondrial reactive oxygen species generation.
It is about the mutagens that causes the genetic disorders. Here I enlist the different responsible proteins whose deficiency or excessive amount cause genetic disorders.
Mechanisms involved in Reactive oxygen species induced sperm damages and thei...rahulvet27
1) Reactive oxygen species (ROS) are produced in greater quantities during sperm cryopreservation and can cause oxidative stress-related damage through lipid peroxidation, DNA damage, apoptosis, motility impairment, and protein damage.
2) Common sources of ROS include immature sperm cells, leukocytes, semen processing techniques, and dissolved oxygen.
3) Amelioration of ROS-induced damage can be achieved through the use of enzymatic antioxidants like catalase and glutathione peroxidase, non-enzymatic antioxidants like vitamin C and E, biological ROS inhibitors from oviductal fluid and seminal plasma, and reducing dissolved oxygen levels in cryopreservation extenders.
EngenuitySC's Science Cafe - March with Dr. Patrick WosterEngenuitySC
This document discusses epigenetic modulation through inhibition of histone demethylases like LSD1. It summarizes that:
1) Polyamino(bis)guanidines and polyaminobiguanides can inhibit the histone demethylase LSD1 in vitro and in human colon cancer cells.
2) These inhibitors are non-competitive inhibitors of LSD1 and promote increased histone H3 lysine 4 dimethylation.
3) One inhibitor, verlindamycin (compound 2d), re-expresses tumor suppressor genes silenced in cancer cells and reduces tumor growth in mouse models of human colon cancer, especially in combination with 5-azacytidine.
Indole-3-carbinol (I3C) is a compound found in cruciferous vegetables that may have anticancer properties. This document summarizes I3C's sources, chemical properties, metabolism, mechanisms of action, and clinical trial data. Key points:
1) I3C is produced from glucosinolates in cruciferous vegetables and may be converted to dimers and trimers in the stomach and intestines.
2) Preclinical studies suggest I3C has anti-inflammatory, antioxidant, and anticancer effects through multiple pathways like NF-kB and Akt.
3) Phase I/II clinical trials show I3C is well tolerated at doses of 200-
Protein aggregation is the most discussed topic as it is being linked to many neurodegenerative diseases. Here, in these slides I have tried to explain about protein aggregation and its mechanism.
This document discusses amyloid induction and inhibition. Amyloid formation is induced through protein misfolding, genetic mutations, and environmental factors. It can be inhibited at several stages, including stabilizing the native protein state, inhibiting aggregation and fibril formation, targeting misfolded proteins and amyloid fibrils through immunotherapy, and inhibiting amyloid precursor transcription through RNA interference. The accumulation of amyloid in tissues leads to amyloidosis and toxicity, which are associated with many neurodegenerative diseases. Research aims to discover inhibitory molecules and therapies that target different stages of amyloid formation and clearance.
factor protector de IL-6 en la insuficiencia renal agudamelissazapataduran
Interleukin-6 plays a protective role in cisplatin-induced acute renal failure through upregulation of anti-oxidative stress factors. The researchers conducted experiments using IL-6 knockout mice to simulate the human condition. They found that lack of IL-6 led to increased lipid peroxidation, showing that IL-6 prevents progression of acute renal failure by reducing oxidative stress. The findings suggest IL-6 promotes protective activities in the kidneys and applying this knowledge could help clinical practice.
This document summarizes the causes and consequences of oxidative stress in spermatozoa. It discusses how spermatozoa are vulnerable to oxidative attack due to their lack of antioxidant protection and high levels of polyunsaturated fatty acids. Oxidative stress can damage sperm membranes through lipid peroxidation, suppressing motility. It also causes DNA damage that is associated with miscarriage and developmental abnormalities. While reactive oxygen species are important for sperm capacitation, excessive levels can overwhelm antioxidant defenses and induce apoptosis. The main source of oxidative stress in spermatozoa is mitochondrial reactive oxygen species generation.
It is about the mutagens that causes the genetic disorders. Here I enlist the different responsible proteins whose deficiency or excessive amount cause genetic disorders.
Mechanisms involved in Reactive oxygen species induced sperm damages and thei...rahulvet27
1) Reactive oxygen species (ROS) are produced in greater quantities during sperm cryopreservation and can cause oxidative stress-related damage through lipid peroxidation, DNA damage, apoptosis, motility impairment, and protein damage.
2) Common sources of ROS include immature sperm cells, leukocytes, semen processing techniques, and dissolved oxygen.
3) Amelioration of ROS-induced damage can be achieved through the use of enzymatic antioxidants like catalase and glutathione peroxidase, non-enzymatic antioxidants like vitamin C and E, biological ROS inhibitors from oviductal fluid and seminal plasma, and reducing dissolved oxygen levels in cryopreservation extenders.
EngenuitySC's Science Cafe - March with Dr. Patrick WosterEngenuitySC
This document discusses epigenetic modulation through inhibition of histone demethylases like LSD1. It summarizes that:
1) Polyamino(bis)guanidines and polyaminobiguanides can inhibit the histone demethylase LSD1 in vitro and in human colon cancer cells.
2) These inhibitors are non-competitive inhibitors of LSD1 and promote increased histone H3 lysine 4 dimethylation.
3) One inhibitor, verlindamycin (compound 2d), re-expresses tumor suppressor genes silenced in cancer cells and reduces tumor growth in mouse models of human colon cancer, especially in combination with 5-azacytidine.
Indole-3-carbinol (I3C) is a compound found in cruciferous vegetables that may have anticancer properties. This document summarizes I3C's sources, chemical properties, metabolism, mechanisms of action, and clinical trial data. Key points:
1) I3C is produced from glucosinolates in cruciferous vegetables and may be converted to dimers and trimers in the stomach and intestines.
2) Preclinical studies suggest I3C has anti-inflammatory, antioxidant, and anticancer effects through multiple pathways like NF-kB and Akt.
3) Phase I/II clinical trials show I3C is well tolerated at doses of 200-
Protein aggregation is the most discussed topic as it is being linked to many neurodegenerative diseases. Here, in these slides I have tried to explain about protein aggregation and its mechanism.
This document discusses amyloid induction and inhibition. Amyloid formation is induced through protein misfolding, genetic mutations, and environmental factors. It can be inhibited at several stages, including stabilizing the native protein state, inhibiting aggregation and fibril formation, targeting misfolded proteins and amyloid fibrils through immunotherapy, and inhibiting amyloid precursor transcription through RNA interference. The accumulation of amyloid in tissues leads to amyloidosis and toxicity, which are associated with many neurodegenerative diseases. Research aims to discover inhibitory molecules and therapies that target different stages of amyloid formation and clearance.
factor protector de IL-6 en la insuficiencia renal agudamelissazapataduran
Interleukin-6 plays a protective role in cisplatin-induced acute renal failure through upregulation of anti-oxidative stress factors. The researchers conducted experiments using IL-6 knockout mice to simulate the human condition. They found that lack of IL-6 led to increased lipid peroxidation, showing that IL-6 prevents progression of acute renal failure by reducing oxidative stress. The findings suggest IL-6 promotes protective activities in the kidneys and applying this knowledge could help clinical practice.
Aging is a phenomena in which the functions, applicability and
resistance of an organism reduces over time. With the globally aging at an accelerating pace, delaying the negative aspects of aging is vital for advancing the human life span and quality of life. The aging of multiple organs can lead to a lot of disease and no exception for cardiovascular system. Actually, one of the primary risk factors for cardiovascular diseases is aging because of altered cardiovascular metabolism resulting in metabolic disorders and inflammation. In this review, we discuss about the relationship of oxidative stress with aging and FoxO proteins, which is essential factor for anti-aging of cardiovascular systems.
Dietary Phytochemicals and Histone Modifications in CancerDr. Supratim Ghatak
1. Histone modifications such as acetylation, methylation, and phosphorylation are altered in cancer and can affect gene expression. Certain plant-derived chemicals like resveratrol, curcumin, and anacardic acid can inhibit histone-modifying enzymes and may have anti-cancer effects.
2. Resveratrol, found in grapes, inhibits HDACs and activates SIRT1, inducing apoptosis in cancer cells by downregulating anti-apoptotic proteins. It also reduces heat shock protein Hsp70 levels in leukemia cells.
3. Further studies are needed to understand the effects of resveratrol on other proteins involved in apoptosis signaling pathways and heat shock transcription factors in cancer
Mitochondrial dysfunction has been identified as an important factor in many diseases and conditions beyond primary mitochondrial disease, including autism, ALS, Parkinson's, Alzheimer's, and diabetes. Exposure to toxins via medication, lifestyle, and the environment may lead to mitochondrial dysfunction, cell damage and organ dysfunction. Join us this month with Dr. Kendall Wallace, Ph.D., DABT, ATS to learn more about mitochondrial disorders which may be acquired by or aggravated by toxins. Dr. Wallace’ primary area of research is the mechanisms of involvement of mitochondria in the origination of metabolic diseases which may be caused by toxicity. - See more at: http://www.mitoaction.org/blog/mitochondrial-disease-and-toxins#sthash.PyxCUqlF.dpuf
The document discusses epigenetics, which refers to changes in gene expression that do not involve changes to DNA sequence. It describes several epigenetic mechanisms including DNA methylation and histone modifications. Epigenetic changes play a role in diseases like cancer, where aberrant patterns of DNA methylation and histone acetylation are common. Emerging therapies target epigenetic processes by inhibiting DNA methylation or histone-modifying enzymes. These therapies aim to reverse epigenetic changes and reactivate genes silenced in cancer.
Protein misfolding occurs when proteins fail to fold into their proper three-dimensional structures, which determines their function. Misfolded proteins can aggregate and form clumps that cause neurodegenerative diseases like Alzheimer's, Parkinson's, ALS, and mental illnesses such as schizophrenia. Specifically, a study identified the misfolded protein collapsin-response mediator protein 1 (CRMP1) as a biological marker for schizophrenia. Protein folding diseases involve either excessive quantities of misfolded proteins accumulating as uncontrolled aggregates, or incomplete folding affecting a protein's normal function.
The document discusses neurodegenerative diseases that are caused by the misfolding and aggregation of proteins, including Alzheimer's disease, Parkinson's disease, ALS, and prion diseases. It describes how antibodies can selectively target misfolded proteins causing disease while sparing native protein structures, providing efficacy through neutralizing toxicity and blocking propagation while maintaining safety by preserving normal function. The document also provides an overview of an assay to quantify aggregated amyloid beta and lists several propagated protein misfolding diseases.
In medicine, proteopathy refers to a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the fuction of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a gain of toxic function) or they can lose their normal function. The proteopathies (also known as proteinopathies, protein conformational disorders, or protein misfolding diseases), include such diseases as Alzheimer's disease, Parkinson's disease, prion disease, type 2 diabetes, amyloidosis, and a wide range of other disorders .
Genetic toxicology involves assessing the effects of physical and chemical agents on DNA and genetic processes in living cells. It examines the health impacts of genetic alterations in somatic and germ cells, mechanisms that induce alterations like DNA damage and repair, and formation of gene mutations. A variety of assays are used to detect genetic alterations, with goals of identifying mutagenic chemicals and repair mechanisms. These assays examine DNA damage, mutations in nonmammalian and mammalian models, and chromosomal aberrations. Germ cell mutagenesis is also evaluated through assays measuring gene mutations and chromosomal alterations.
The document discusses a study that examined copper and malondialdehyde levels in seminal plasma of oligospermic (low sperm count) and normospermic (normal sperm count) men in Diyala, Iraq. The study found that seminal plasma copper levels decreased non-significantly in oligospermic men compared to controls, while malondialdehyde levels, a marker of lipid peroxidation, were significantly elevated in oligospermic men. This suggests oxidative stress may play a role in male infertility.
Protein synthesis and disposal occur in highly regulated manner. In cells protein folding is assisted by special kind of proteins called as molecular chaperones and disturbances in protein quality control leads to deadly diseases
This document discusses the molecular basis of aging and longevity. It covers several topics: genes and aging pathways like DNA repair and insulin signaling; environmental and epigenetic factors such as oxidative damage, diet, and calorie restriction; and promoting longevity. Key points include conserved genetic pathways regulating aging across species, the role of genes encoding DNA repair enzymes and insulin signaling proteins, and how calorie restriction and reducing insulin/IGF-1 signaling can increase longevity in various organisms.
Fetal alcohol spectrum disorders the epigenetic perspective1 philip c. haycockBARRY STANLEY 2 fasd
An excellent account of the epigenetic consequences of preconceptual alcohol and prenatal alcohol. Although published ten years ago subsequent research confirms Dr Haycock’s conclusions.
ENDOPLASMIC RETICULUM STRESS IN DIABETIC COMPLICATIONSBasweshwar Gawali
The document discusses endoplasmic reticulum (ER) stress in diabetic complications. It begins by providing background on diabetes and the role of the ER. The ER is responsible for protein folding, modification and transport. Under stress, misfolded proteins accumulate and activate the unfolded protein response (UPR) pathway involving IRE1, PERK and ATF6. Persistent ER stress can lead to apoptosis and organ dysfunction. Conditions like diabetes with high protein load and misfolding in the pancreas and other tissues cause ER stress. Targeting ER stress pathways may provide novel treatment strategies for diabetes and related complications.
Metal ions are used in medicine for both diagnostic and treatment purposes. Some metals like technetium, gadolinium, and iron are used in medical imaging techniques like MRI. Platinum compounds like cisplatin are commonly used to treat cancers by binding to DNA and interfering with cell division. While effective, metals can cause side effects if levels become unbalanced or toxicity occurs from treatment. Precise application of metal ions exploits their properties for medical benefit.
This document discusses protein breakdown and the ubiquitin-proteasome pathway. It notes that all proteins continually turnover and are broken down and replaced. The ubiquitin-proteasome pathway is the main system for degrading intracellular proteins in cells. In this pathway, target proteins are tagged with ubiquitin molecules and then degraded by the 26S proteasome complex. This pathway is responsible for the normal turnover of long-lived proteins as well as the accelerated breakdown of proteins in disease states. It plays an important role in various cellular processes like quality control, adaptation to changes, and immune function.
The document discusses the role of autophagy in the immune system. It describes how autophagy functions in innate immunity through interactions with pattern recognition receptors like TLRs, NLRs, and RLRs. Autophagy helps clear pathogens and regulate cytokine production. The document also examines the role of autophagy in adaptive immunity, particularly antigen presentation through MHC class I and II pathways. Finally, it explores how autophagy impacts T cell and B cell development and homeostasis.
This study examined whether contractile activity in cardiomyocytes regulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production via focal adhesion kinase (FAK)-dependent signaling. The researchers treated spontaneously contracting neonatal rat ventricular myocytes with inhibitors of contraction and found they reduced iNOS expression and NO production by inhibiting FAK and AKT phosphorylation. Inhibiting FAK or PI3K also eliminated contraction-induced iNOS expression. Knockdown of FAK reduced AKT phosphorylation and iNOS expression, whereas overexpression of constitutively active FAK or AKT reversed the inhibitory effect of contraction inhibitors. Thus, contraction induces iNOS expression and NO production via a FAK-PI3K-AK
1) The study found that inhibiting HDAC3 with the selective inhibitor MI192 increased tubulin acetylation levels and disrupted microtubule dynamics in prostate cancer cells.
2) Knockdown of HDAC3 using siRNA also increased tubulin acetylation levels, while overexpression of HDAC3 reduced acetylation.
3) However, in vitro assays showed that the HDAC3-SMRT-DAD complex did not directly deacetylate tubulin, suggesting HDAC3 modulates tubulin acetylation indirectly.
This document discusses the potential health benefits of resveratrol based on scientific studies. It summarizes research showing that resveratrol may help prevent cancers, reduce cardiovascular risks, protect arteries, repair DNA damage, and prevent hepatic steatosis. The document recommends that taking resveratrol daily could provide benefits similar to stopping smoking, with low cost and no reported side effects.
Mitochondria and MitoQ – A research updatemitoaction
Greg Macpherson presented an update on research related to mitochondria and MitoQ. Some key points include:
- MitoQ was discovered at Otago University in New Zealand and is a mitochondria-targeted antioxidant.
- Over 200,000 patient months of experience and availability in over 100 countries.
- Research has included over 50 million USD invested and 200+ published papers involving 70+ disease models.
- Clinical trials have shown benefits for conditions such as fibromyalgia, chronic fatigue syndrome, and type 2 diabetes.
- Mouse and human research has demonstrated reductions in oxidative stress, inflammation, and markers of disease from conditions such as liver fibrosis when taking MitoQ.
- Future research
This document summarizes research on the role of reactive oxygen species (ROS) in human fertility. It finds that ROS are produced naturally in the body but can also be generated by leukocytes, abnormal sperm, and other sources. While low levels play a role in fertilization, high levels of ROS can damage lipids, proteins, DNA and impair sperm motility and the ability of sperm to fuse with eggs. This leads to decreased sperm counts and quality, as well as DNA damage that may cause embryo death, miscarriage or birth defects. Antioxidants normally neutralize ROS, but when levels are too high it causes oxidative stress that contributes to infertility in both males and females.
Male infertility can be caused by structural or functional abnormalities in sperm, including low sperm count, low motility, and abnormal forms. Oxidative stress from reactive oxygen species is another leading cause, as it can damage sperm DNA and membranes. The body normally defends against oxidative stress through antioxidant enzymes and compounds in seminal plasma. However, oxidative stress overwhelms these defenses in around 25-40% of infertile men. Various antioxidants taken as supplements, either alone or in combination, have been shown to reduce oxidative stress levels, boost sperm parameters, and improve fertility rates. These include CoQ10, lycopene, mixed carotenoids, omega-3 fatty acids, vitamin C, vitamin E, selenium, zinc
Aging is a phenomena in which the functions, applicability and
resistance of an organism reduces over time. With the globally aging at an accelerating pace, delaying the negative aspects of aging is vital for advancing the human life span and quality of life. The aging of multiple organs can lead to a lot of disease and no exception for cardiovascular system. Actually, one of the primary risk factors for cardiovascular diseases is aging because of altered cardiovascular metabolism resulting in metabolic disorders and inflammation. In this review, we discuss about the relationship of oxidative stress with aging and FoxO proteins, which is essential factor for anti-aging of cardiovascular systems.
Dietary Phytochemicals and Histone Modifications in CancerDr. Supratim Ghatak
1. Histone modifications such as acetylation, methylation, and phosphorylation are altered in cancer and can affect gene expression. Certain plant-derived chemicals like resveratrol, curcumin, and anacardic acid can inhibit histone-modifying enzymes and may have anti-cancer effects.
2. Resveratrol, found in grapes, inhibits HDACs and activates SIRT1, inducing apoptosis in cancer cells by downregulating anti-apoptotic proteins. It also reduces heat shock protein Hsp70 levels in leukemia cells.
3. Further studies are needed to understand the effects of resveratrol on other proteins involved in apoptosis signaling pathways and heat shock transcription factors in cancer
Mitochondrial dysfunction has been identified as an important factor in many diseases and conditions beyond primary mitochondrial disease, including autism, ALS, Parkinson's, Alzheimer's, and diabetes. Exposure to toxins via medication, lifestyle, and the environment may lead to mitochondrial dysfunction, cell damage and organ dysfunction. Join us this month with Dr. Kendall Wallace, Ph.D., DABT, ATS to learn more about mitochondrial disorders which may be acquired by or aggravated by toxins. Dr. Wallace’ primary area of research is the mechanisms of involvement of mitochondria in the origination of metabolic diseases which may be caused by toxicity. - See more at: http://www.mitoaction.org/blog/mitochondrial-disease-and-toxins#sthash.PyxCUqlF.dpuf
The document discusses epigenetics, which refers to changes in gene expression that do not involve changes to DNA sequence. It describes several epigenetic mechanisms including DNA methylation and histone modifications. Epigenetic changes play a role in diseases like cancer, where aberrant patterns of DNA methylation and histone acetylation are common. Emerging therapies target epigenetic processes by inhibiting DNA methylation or histone-modifying enzymes. These therapies aim to reverse epigenetic changes and reactivate genes silenced in cancer.
Protein misfolding occurs when proteins fail to fold into their proper three-dimensional structures, which determines their function. Misfolded proteins can aggregate and form clumps that cause neurodegenerative diseases like Alzheimer's, Parkinson's, ALS, and mental illnesses such as schizophrenia. Specifically, a study identified the misfolded protein collapsin-response mediator protein 1 (CRMP1) as a biological marker for schizophrenia. Protein folding diseases involve either excessive quantities of misfolded proteins accumulating as uncontrolled aggregates, or incomplete folding affecting a protein's normal function.
The document discusses neurodegenerative diseases that are caused by the misfolding and aggregation of proteins, including Alzheimer's disease, Parkinson's disease, ALS, and prion diseases. It describes how antibodies can selectively target misfolded proteins causing disease while sparing native protein structures, providing efficacy through neutralizing toxicity and blocking propagation while maintaining safety by preserving normal function. The document also provides an overview of an assay to quantify aggregated amyloid beta and lists several propagated protein misfolding diseases.
In medicine, proteopathy refers to a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the fuction of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a gain of toxic function) or they can lose their normal function. The proteopathies (also known as proteinopathies, protein conformational disorders, or protein misfolding diseases), include such diseases as Alzheimer's disease, Parkinson's disease, prion disease, type 2 diabetes, amyloidosis, and a wide range of other disorders .
Genetic toxicology involves assessing the effects of physical and chemical agents on DNA and genetic processes in living cells. It examines the health impacts of genetic alterations in somatic and germ cells, mechanisms that induce alterations like DNA damage and repair, and formation of gene mutations. A variety of assays are used to detect genetic alterations, with goals of identifying mutagenic chemicals and repair mechanisms. These assays examine DNA damage, mutations in nonmammalian and mammalian models, and chromosomal aberrations. Germ cell mutagenesis is also evaluated through assays measuring gene mutations and chromosomal alterations.
The document discusses a study that examined copper and malondialdehyde levels in seminal plasma of oligospermic (low sperm count) and normospermic (normal sperm count) men in Diyala, Iraq. The study found that seminal plasma copper levels decreased non-significantly in oligospermic men compared to controls, while malondialdehyde levels, a marker of lipid peroxidation, were significantly elevated in oligospermic men. This suggests oxidative stress may play a role in male infertility.
Protein synthesis and disposal occur in highly regulated manner. In cells protein folding is assisted by special kind of proteins called as molecular chaperones and disturbances in protein quality control leads to deadly diseases
This document discusses the molecular basis of aging and longevity. It covers several topics: genes and aging pathways like DNA repair and insulin signaling; environmental and epigenetic factors such as oxidative damage, diet, and calorie restriction; and promoting longevity. Key points include conserved genetic pathways regulating aging across species, the role of genes encoding DNA repair enzymes and insulin signaling proteins, and how calorie restriction and reducing insulin/IGF-1 signaling can increase longevity in various organisms.
Fetal alcohol spectrum disorders the epigenetic perspective1 philip c. haycockBARRY STANLEY 2 fasd
An excellent account of the epigenetic consequences of preconceptual alcohol and prenatal alcohol. Although published ten years ago subsequent research confirms Dr Haycock’s conclusions.
ENDOPLASMIC RETICULUM STRESS IN DIABETIC COMPLICATIONSBasweshwar Gawali
The document discusses endoplasmic reticulum (ER) stress in diabetic complications. It begins by providing background on diabetes and the role of the ER. The ER is responsible for protein folding, modification and transport. Under stress, misfolded proteins accumulate and activate the unfolded protein response (UPR) pathway involving IRE1, PERK and ATF6. Persistent ER stress can lead to apoptosis and organ dysfunction. Conditions like diabetes with high protein load and misfolding in the pancreas and other tissues cause ER stress. Targeting ER stress pathways may provide novel treatment strategies for diabetes and related complications.
Metal ions are used in medicine for both diagnostic and treatment purposes. Some metals like technetium, gadolinium, and iron are used in medical imaging techniques like MRI. Platinum compounds like cisplatin are commonly used to treat cancers by binding to DNA and interfering with cell division. While effective, metals can cause side effects if levels become unbalanced or toxicity occurs from treatment. Precise application of metal ions exploits their properties for medical benefit.
This document discusses protein breakdown and the ubiquitin-proteasome pathway. It notes that all proteins continually turnover and are broken down and replaced. The ubiquitin-proteasome pathway is the main system for degrading intracellular proteins in cells. In this pathway, target proteins are tagged with ubiquitin molecules and then degraded by the 26S proteasome complex. This pathway is responsible for the normal turnover of long-lived proteins as well as the accelerated breakdown of proteins in disease states. It plays an important role in various cellular processes like quality control, adaptation to changes, and immune function.
The document discusses the role of autophagy in the immune system. It describes how autophagy functions in innate immunity through interactions with pattern recognition receptors like TLRs, NLRs, and RLRs. Autophagy helps clear pathogens and regulate cytokine production. The document also examines the role of autophagy in adaptive immunity, particularly antigen presentation through MHC class I and II pathways. Finally, it explores how autophagy impacts T cell and B cell development and homeostasis.
This study examined whether contractile activity in cardiomyocytes regulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production via focal adhesion kinase (FAK)-dependent signaling. The researchers treated spontaneously contracting neonatal rat ventricular myocytes with inhibitors of contraction and found they reduced iNOS expression and NO production by inhibiting FAK and AKT phosphorylation. Inhibiting FAK or PI3K also eliminated contraction-induced iNOS expression. Knockdown of FAK reduced AKT phosphorylation and iNOS expression, whereas overexpression of constitutively active FAK or AKT reversed the inhibitory effect of contraction inhibitors. Thus, contraction induces iNOS expression and NO production via a FAK-PI3K-AK
1) The study found that inhibiting HDAC3 with the selective inhibitor MI192 increased tubulin acetylation levels and disrupted microtubule dynamics in prostate cancer cells.
2) Knockdown of HDAC3 using siRNA also increased tubulin acetylation levels, while overexpression of HDAC3 reduced acetylation.
3) However, in vitro assays showed that the HDAC3-SMRT-DAD complex did not directly deacetylate tubulin, suggesting HDAC3 modulates tubulin acetylation indirectly.
This document discusses the potential health benefits of resveratrol based on scientific studies. It summarizes research showing that resveratrol may help prevent cancers, reduce cardiovascular risks, protect arteries, repair DNA damage, and prevent hepatic steatosis. The document recommends that taking resveratrol daily could provide benefits similar to stopping smoking, with low cost and no reported side effects.
Mitochondria and MitoQ – A research updatemitoaction
Greg Macpherson presented an update on research related to mitochondria and MitoQ. Some key points include:
- MitoQ was discovered at Otago University in New Zealand and is a mitochondria-targeted antioxidant.
- Over 200,000 patient months of experience and availability in over 100 countries.
- Research has included over 50 million USD invested and 200+ published papers involving 70+ disease models.
- Clinical trials have shown benefits for conditions such as fibromyalgia, chronic fatigue syndrome, and type 2 diabetes.
- Mouse and human research has demonstrated reductions in oxidative stress, inflammation, and markers of disease from conditions such as liver fibrosis when taking MitoQ.
- Future research
This document summarizes research on the role of reactive oxygen species (ROS) in human fertility. It finds that ROS are produced naturally in the body but can also be generated by leukocytes, abnormal sperm, and other sources. While low levels play a role in fertilization, high levels of ROS can damage lipids, proteins, DNA and impair sperm motility and the ability of sperm to fuse with eggs. This leads to decreased sperm counts and quality, as well as DNA damage that may cause embryo death, miscarriage or birth defects. Antioxidants normally neutralize ROS, but when levels are too high it causes oxidative stress that contributes to infertility in both males and females.
Male infertility can be caused by structural or functional abnormalities in sperm, including low sperm count, low motility, and abnormal forms. Oxidative stress from reactive oxygen species is another leading cause, as it can damage sperm DNA and membranes. The body normally defends against oxidative stress through antioxidant enzymes and compounds in seminal plasma. However, oxidative stress overwhelms these defenses in around 25-40% of infertile men. Various antioxidants taken as supplements, either alone or in combination, have been shown to reduce oxidative stress levels, boost sperm parameters, and improve fertility rates. These include CoQ10, lycopene, mixed carotenoids, omega-3 fatty acids, vitamin C, vitamin E, selenium, zinc
Oxidative stress from reactive oxygen species can impair sperm function and contribute to male infertility. Antioxidants may help reduce oxidative stress and improve fertility outcomes. Oral antioxidant supplementation in men with oxidative stress issues has been shown to increase pregnancy and live birth rates when undergoing assisted reproductive technologies. However, more research is still needed to determine the best candidates, formulations, dosages and duration of treatment for oral antioxidant therapy in cases of male infertility related to oxidative stress.
The document discusses DNA repair mechanisms in human lymphocytes. It describes how oxidized purines in DNA are repaired through the base excision repair pathway involving the OGG1 glycosylase. This repair requires activation by the transcription factor NF-YA, which upregulates OGG1 expression when DNA is at risk of oxidation. The repair of oxidized bases by OGG1 in human lymphocytes is slow but can be activated by phytohemagglutinin. Disruption of this global repair of oxidized purines may be due to downregulation of OGG1. A second document discusses how green tea acts as an antioxidant to protect against oxidative stress and influence DNA damage and repair through activation of the Nrf2 transcription factor and upreg
Effect of Selenium in Treatment of Male Infertility by Mossa M Morbat, Azzawi M Hadi* and Dekhel H Hadri in Experimental Techniques in Urology & Nephrology
The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment
of the risk/benefit profile. Nutritional Journal
1) The document discusses the role of micro nutrients and oxidative stress in male infertility. It notes that oxidative stress can damage sperm DNA, mitochondria, and membranes and is a major cause of male infertility.
2) It provides information on various antioxidants like CoQ10, melatonin, which help reduce oxidative stress levels in semen. CoQ10 supports energy production in sperm while melatonin is a potent antioxidant and regulates testosterone secretion.
3) Maintaining a balance between reactive oxygen species and antioxidant levels is important for sperm function and fertility potential. Supplements with antioxidants can help address nutritional deficiencies and reduce oxidative stress related sperm damage leading to infertility.
Free Radical injury and acute phase reactantsDr Siddartha
Free radicals are unstable molecules that can cause oxidative damage. They play both beneficial and harmful roles in the body. Antioxidants help defend against free radical damage through enzymatic and non-enzymatic mechanisms. Acute phase proteins are hepatic proteins whose levels change in response to inflammation or infection, and include positive and negative proteins like C-reactive protein and haptoglobin. Oxidative stress and free radicals are implicated in many diseases while antioxidants may help prevent disease.
This document discusses new strategies for combating cancer through molecular biology approaches. It describes prevention strategies that focus on pre-invasive lesions by inhibiting carcinogen initiation events, cell proliferation associated with promotion, or the development of the invasive phenotype in precancerous lesions. Targets for prevention strategies include biochemical species produced by carcinogens and aberrantly expressed proteins from genetic/environmental risk factors. Gene expression profiling using cDNA microarrays can help understand carcinogenesis at the molecular level and identify new therapeutic targets. The document also discusses inhibiting metastasis through strategies like modifying cell adhesion with MMP inhibitors or anticoagulants, and inhibiting angiogenesis. Gene therapy approaches for cancer treatment aim to correct genetic mutations or deliver therapeutic genes to stimulate anti-tumor immune
Oxidative Stress is a major contributor of unexplained female infertility and male factor infertility.Recent Cochrane database metanalysis suggests there is a low but significant improvement in fertility with use of various micronutrients and antioxidant supplements.
Male factor infertility accounts for 50% of infertility cases. Oxidative stress from reactive oxygen species is an important cause of male infertility. High levels of ROS can damage sperm cells through lipid peroxidation and DNA fragmentation. Antioxidant supplements like vitamins C and E, carnitine, N-acetyl cysteine, CoQ10, and zinc can help reduce oxidative stress by scavenging excess ROS in semen. This may help improve sperm parameters and treat infertility caused by oxidative stress.
Vitamin C, glutathione, and various enzymes have radioprotective effects against cellular damage caused by ionizing radiation. Vitamin C is an antioxidant that can scavenge reactive oxygen species produced by radiation and protect DNA and membranes. Glutathione is also a free radical scavenger that protects against radiation damage. Various enzymes also help scavenge free radicals produced by radiation. The presentation concludes that vitamin C, glutathione, and enzymes play an important role in mitigating the effects of ionizing radiation exposure.
_Role_of_free_radicals_in_cancer M pharmacy PharmacologyAyodhya Paradhe
Free radicals are reactive molecules that can damage cells and DNA. High levels of free radicals and oxidative stress can lead to mutations that cause cancer. Many cancer-causing factors like tobacco, UV light, and inflammation increase free radical production. Curcumin and vitamins C and E are antioxidants that can prevent cancer by reducing oxidative stress and blocking enzymes involved in cancer formation and growth. Intravenous vitamin C treatment for cancer works by increasing oxidative stress in cancer cells through hydrogen peroxide production, altering gene expression, and inhibiting tumor invasion and metastasis. Antioxidants and lifestyle changes may help prevent cancer by lowering free radical levels and reducing cancer risk from environmental exposures.
External agents like carcinogens, pollutants, ionizing radiations produce oxidative stress in living cells generating reactive oxygen
species [ROS]. Cells have built in defense against these reactive species and keep a balance between generated ROS and their
neutralization by endogenous antioxidants [AO]. In addition, many antioxidants present in our diets react with the ROS and make
them inactive. The maintenance of balance is a continuous process inside cells to keep them functioning normally. When
generation of ROS exceeds the level of endogenous and externally added AOs , cells are driven to pathogenic state leading to
diseases. A variety of dietary AOs are available from various sources of fruits and vegetables. This paper aims to review the
molecular mechanisms of oxidative stress, generation and reactions of ROS with vital molecules such as DNA, Protein and
membrane and involvement of ROS in the induction of cancer and other diseases. An attempt is made to suggest ways to reduce
cancer incidence risks , need to modify dietary foods by consuming vegetables, fruits for chemo prevention. An example has been
given to emphasize the role of curcumin as an antioxidant in the mechanism of chemoprevention.
Keywords: Oxidative stress, Carcinogens, ROS, Antioxidants, Chemoprevention.
This presentation illustrates the various pathways of development of AD ,including the recent molecular pathways , and their implication in early diagnosis and therapy .
Protandim: PubMed.Gov Clinical Studies and MoreLifeVantage
This document summarizes 5 peer-reviewed studies on the effects of the dietary supplement Protandim. The studies found that Protandim:
1) Increased antioxidant enzymes SOD and catalase in humans, reducing oxidative stress by 40-70% within 30-120 days.
2) Prevented skin cancer in mice - 33% developed no cancer at all and the rest developed less aggressive cancers with fewer tumors.
3) Synergistically increased the antioxidant glutathione by 300% in 30 days through upregulating Nrf2 pathways.
4) Protected rat hearts from failure in a model of lung disease by reducing fibrosis and preserving heart function.
5) Improved markers of oxidative
By Prof. ATEF DONIA Professor of Pediatrics Al Azhar University
The role of reactive oxygen species (ROS) in pathogenesis of common disorders of the preterm infant.
The unique susceptibility of premature infants to oxidative stress. Potential for therapeutic interventions using enzymatic and/or non-enzymatic antioxidants
The document analyzes oxidative stress markers by discussing topics like reactive oxygen species, oxidative stress-induced diseases, antioxidants, antioxidant responsive elements, gene expression profiles related to oxidative stress, and the nuclear factor Nrf2. It provides details on how Nrf2 regulates genes involved in the oxidative stress response and its interaction with the protein Keap1 that mediates Nrf2 degradation in the cytoplasm. The key roles of cysteine residues in Keap1 and Nrf2 in regulating the retention and release of Nrf2 are also summarized.
Neurodegeneration: Factors Involved and Therapeutic Strategiesinventionjournals
Neurodegenerative disorders are disorders of the nervous system which are characterized by a loss of neuronal structure and function. These changes lead to a loss of several abilities that include cognition and movement as observed in Alzheimer’s and Parkinson’s. Several factors like oxidative stress and protein misfolding have been found to play a vital role in the etiology of common neurological disorders. Whether these factors contribute to the progression of the disorders or are a consequence still remains elusive. Inspite of attempts to elucidate the molecular and pathological mechanisms of these pathways, many aspects still remain unclear. However, newer areas of therapeutic interventions like stem cell therapy and anti-oxidant therapy are now being explored as potential treatments. The aim of this review is to study the various factors that are associated with neurodegeneration along with recent therapeutic strategies that are being employed in an attempt to treat neurodegenerative disorders.
Study of Trace Elements Selenium, Copper, Zinc and Manganese Level in Polycys...AnuragSingh1049
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women, trace elements play an important role in PCOS, selenium performs various biological functions such as defense against oxidative stress, immune function and thyroid function, polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women, trace Elements have important role in PCOS, selenium is involved in many biological functions, such as, protection against oxidative stress, immune function and thyroid function, Copper, zinc and manganese are essential micronutrients that have been integrated into various proteins and metalloenzymes and are active in the metabolic process of cells and in oxidative stress pathways that can lead to oxidative stress.
One hundred and twenty-four of patients' women with poly cystic ovarian syndrome (PCOS) patients and 56 normal ovulatory women participated in the study. Seleniumand serum Copper, zinc and manganese were measured by using flame atomic absorption spectrometry (FAAS).
Similar to Role of Antioxidants in the Treatment of Male Infertility-Crimson Publishers (20)
Recently published papers have defined the clinical characteristics and overall outcomes of COVID-19 patients with the influence on the healthcare system. Especially, general surgeons are uniquely affected due to the broad range of procedures they perform, many of which are conducted routinely in the outpatient setting. This report aims to represent the clinical presentation and outcomes of elective surgical patients during the COVID-19 epidemic.
Extramedullary hematopoiesis (EMH) occurs when hematopoietic tissue develops outside the bone marrow, such as in the liver, spleen, or paravertebral tissues, as a compensatory mechanism for ineffective hematopoiesis. EMH often presents as pseudotumors that can be mistaken for other tumors. The underlying cause is usually a hematopoietic disorder like thalassemia or myeloproliferative neoplasm. A thorough medical history, physical exam, blood tests, and imaging tests are needed to diagnose EMH and identify the cause. Treatment focuses on managing the underlying disorder, as this will often resolve the EMH without need for surgery. A hematologist's evaluation is
Dunbar syndrome or celiac artery compression syndrome was described for the first time by Harjola in 1963. It’s an infrequent clinical condition, with few criteria for diagnosis and with obscure pathophysiology. It is usually associated with an extrinsic compression upon the celiac axis near its takeoff from the aorta by fibrous diaphragmatic bands or sympathetic
neural fibers. This syndrome is as uncommon cause for upper abdominal angina. The classic sympthoms include vomiting associated to pos prandial pain, weight loss and soufle
in the epigastric region. Diagnosis is made by abdominal angiotomography, arteriography and magnetic resonance imaging. Surgical ligament release is indicated in case of severe
compression of the celiac trunk or in patient’s refractory to clinical treatment [1].
Female genital mutilation has been condemned far more than male genital mutilation. There seems to be a conspiracy in the scientific community to ignore the benefits of the intact
prepuce (foreskin) and to deny the horrors of male genital mutilation. Science and human rights must always trump and triumph over superstition. The prepuce is on the penis for
a purpose. The foreskin/prepuce is not something to be jettisoned like the umbilical cord.When the umbilical cord is severed neither baby nor mother feel any pain. Why? Because
there are no nerves in the umbilical cord.
Mathematical modeling of the structure of vortex zones between periodic surface-located flow turbulators of a semicircular and square cross-section is carried out on the basis of multi-block computational technologies based on the solution of the factorized finite-volume method of the Reynolds equations (closed with the help of the Menter shear stress transfer
mode) and the energy equation (on different-scale intersecting structured grids). This method was previously successfully applied and verified by experiment. An exhaustive analysis of the corresponding streamlines is presented, proving the advantage of abruded turbulators.
The SARS-CoV 2 pandemic, since its origin in China as a cluster of pneumonia cases, had reached almost every part of the world and had killed more than one million people
worldwide [1]. The case fatality differs substantially between countries along with the number of symptomatic patients, sequelae of the disease and those who require intensive lifecare
support. Such a perceived difference can be attributed to macroecological dissimilarities like the general well-being of the population and a more extent, its demographic structure.
The demographic characteristics, most notably the age structure and population density, has important implications in the spread of infectious diseases [2,3]. Like most of the infectious
diseases we have known so far, COVID-19 is seen more severely in groups like the elderly and those with comorbidities [4,5]. Robustness of the health system and abundance of resources might have helped the western countries to report proportionately a greater number of cases. However huge proportion of elderly population in these countries might have contributed to higher reporting of severe illness and deaths in these countries [6].
“Occam’s Razor is a scientific and philosophical rule that entities should not be multiplied unnecessarily which is interpreted as requiring that the simplest of competing theories be preferred to the more complex or that explanations of unknown phenomena be sought first in terms of known quantity”. [1] Merriam Webster Dictionary, in other words, Occam’s razor says that, of two explanations that account for all the facts, the simpler one is more likely to be correct. “The greatest disorder of the intellect is to believe things because one wishes they were so” [2] Louis Pasteur, 1875. Supposing a man finds a watch. Deliberately or by accident the man smashes the watch to smithereens.
:Extraocular foreign bodies (EOFBs) are a common presentation to the emergency
department (ED). Given that inadequate management can result in severe complications including visual
impairment, ED clinicians may be overly cautious and often schedule patient reviews in the ED even
where it is unnecessary, placing a burden on hospital resources.
Occurrence of a mural thrombus in a diseased descending thoracic aorta (atherosclerotic or aneurysmal) is a well-known and commonly encountered vascular entity. However, thrombus formation in a normal appearing descending thoracic aorta (NADTA) is rarely reported in literature so far. We present an
unusual case report with a brief literature review of an aortic mural thrombus (AMT) in descending thoracic aorta in a young male. He presented at our center in the emergency department with acute onset abdominal pain and underwent a contrast enhanced CT scan that confirmed mural thrombus in
NADTA.
Two case reports: the first, 50-year-old male patient, A.M.B., who suffered from hemorrhoids (2003 to 2005). Moisturizers, medications and cauterization were not successful. The patient started treatment with auricular acupuncture and apex ear bloodletting. He also received measurement of the
chakras 10 years later, which attested his chakras were rated at the minimum level of energy (1) of 8. The second, a 38-year-old male patient, started treatment with ancient medical tools for vitiligo. On the middle of the treatment, he reported to have symptoms of hemorrhoids. Treatment was the same done in case 1 and received measurement of the chakras.
Neuroblastomas are rare extracranial tumors of the pediatric population arising from cells of the embryological sympathetic nervous system. These malignancies most commonly occur in the abdomen, but other sites include the chest, neck, and pelvis with a predisposition for lymphatic and hematogenous
spread. Metastasis to the bone is a poor prognostic indicator, requiring surgical excision and other extensive medical management.
Pilonidal sinus disease is a soft tissue infection. It presents either acutely with abscess or the chronic form of sinus formation. The disease affects multiple body regions but the commonest is the sacrococcygeal region. There are different treatment strategies ranging from simple incision and
drainage of an abscess to complex constructive procedures.
Papua New Guinea has about seven active mining and exploration activities for minerals like gold, copper, and other minor minerals. Each is managed by different company and
together employs about ten thousand workers. A fifth of this would be foreign workers. Most of the Mine workers that are screened at the Employees Health and Wellness clinics tend to
have similar compounding health risks
Inflammatory fibroid polyp (IFP) is a rare benign lesion, originating from the submucosa in the gastrointestinal tract. It generally appears as an isolated benign lesion, rarely located at the level of the ileum. Its origin is controversial. Clinical presentation varies depending on its location; invagination and
obstruction are the most common indicative symptoms when the polyp is located at the level of the small intestine. We report the case of a 60-year old patient with abdominal pain, nausea and vomiting and a personal history of intermittent constipation. Radiological imaging objectified ileo-ileal invagination
completely obstructing the ileum light. Segmental resection of the obstructed ileal segment and terminalterminal anastomosis were performed. The final diagnosis of IFP was established using histological examination.
Candida septic arthritis is a debilitating condition affecting joint function. Candida tropicalis, an organism found in normal human flora is noted to be the third most common pathogenic yeast in the elderly and immunosuppressed population. Infections are rare in the US, typically limited to the neonate
and elderly populations. Most infections occur in the south America and southeast Asian regions. In the last 2 decades, Tropialis infection rates have risen impart due to antifungal resistance. We present a case of Candida tropicalis infection in the knee of a 13-year-old female with a past history of relapsed Acute Myeloid Leukemia following bone marrow transplant, pancytopenia and graft vs. host disease.
When properly performed, the true Maze procedure is highly effective to eliminate any type of atrial fibrillation or flutter. Since non-paroxysmal atrial fibrillation is sustained by macro-reentrant circuits located anywhere in both atria, a full bi-atrial lesion pattern is the best way to approach all possible causes in one single step. As we move into less invasive surgical techniques, we must more clearly maintain the
scope of the Maze procedure. Difficult approaches are oftentimes the source for incomplete, unsuccessful,
and frustrated forms of the Maze. T
The discoveries include 2 new vascular shocks, namely Volumetric Overload Shocks (VOS) that complicate fluid therapy in hospitals. Proving a physiological law of Starling wrong and providing the correct replacement which is the hydrodynamic of the porous orifice (G) tube. Revealing many errors and misconceptions on fluid therapy and reporting its corrections. It all started with an investigation aimed
at understanding a rare obscure syndrome that kills patients in Urology; the Transurethral Resection of
The Prostate (TURP) syndrome.
A 10-year-old boy with a history of repaired tetralogy of Fallot underwent cardiac catheterization for recurrent left pulmonary artery stenosis. During the procedure, the patient's capnogram waveform displayed an unusual variable plateau pattern. This was attributed to ventilation-perfusion abnormalities from the critical left pulmonary artery stenosis, which caused differential lung perfusion with only 10% perfusion to the left lung. Balloon angioplasty and stent placement of the left pulmonary artery immediately normalized the capnogram waveform. The case report discusses how capnography can detect critical perfusion abnormalities through abnormal waveform patterns.
The objective of this letter is to report recent advances on the diagnosis and therapy of the loin pain hematuria syndrome (LPHS). The patho-aetiological link of LPHS with symptomatic
nephroptosis (SN) is a novel discovery of the 21st century that was first preliminary reported in 2002 [1]. The link was confirmed in 2016 in an article that précised the exact pathoaetiology of LPHS; ischemic nephritis and sympathetic neuropathy of SN. It also advanced a 100% curative therapy for LPHS namely; the renal sympathetic denervation and nephropexy (RSD&N) surgery [2].
Bortezomib is a proteasome inhibitor approved for the treatment of multiple myeloma and has known manageable toxicities. Blepharitis is an inflammatory condition of the eyelid that leads to formation of chalazia both causing visual field disturbance. Bortezomib induced blepharitis has not been
well reported in the literature.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
One health condition that is becoming more common day by day is diabetes.
According to research conducted by the National Family Health Survey of India, diabetic cases show a projection which might increase to 10.4% by 2030.
2. How to cite this article: Khaled Gadallah, Abeel A M.Role of Antioxidants in the Treatment of Male Infertility. Surg Med Open Acc J. 1(2).SMOAJ.000507. 2019.
Surgical Medicine Open Access Journal
2/10
Surg Med Open Acc J
Volume 1 - Issue - 2
ROS levels can affect sperm structural and functional integrity
including motility, morphology, count and viability, thereby making
it one of the important etiologies of male factor infertility. High ROS
concentrations in infertile men have been associated with DNA
fragmentation and poor chromatin packing. Sperm DNA damage
may decrease fertilization rates, reduce implantation, impair
embryonic development and increase miscarriage/pregnancy loss
and the potential for birth defects [10]. ROS affect mitochondrial
or nuclear DNA of sperm at an amino acid or molecular level in
the form of base modification (especially guanine), attacking the
phosphor-di-ester backbones and producing base-free sites, point
mutations, polymorphisms, deletions, translocations, strand breaks
and chromatin cross-links, frame shifts and even rearranging
chromosomes [11].
Sperm chromatin has a highly condensed and organized
structure that helps to protect it from oxidative damage, but when
compaction is poor and chromatin protamination is incomplete,
spermDNAismorevulnerabletoROS.DNAdamageisacontributory
factor to apoptosis [12] and in cases of more severe damage of
spermatozoa, apoptosis results in low sperm counts characteristic
of idiopathic male factor infertility [13].
Alleviation of oxidative stress and potential treatment
strategies
Treatment of oxidative stress-associated male infertility
has been studied widely in patients with varicocele-associated
subfertility and unexplained infertility. In these patients, treatment
strategies such as surgical varicocele repair (varicocelectomy) and
oral antioxidant therapy have been used.
Oral antioxidant therapy
In spite of the conflicting data, many urologists prescribe
oral antioxidant therapy for men with clinical subfertility with
or without varicocele [14]. The rationale for recommending oral
antioxidant therapy is based on the premise that seminal oxidative
stress is due in part to a deficiency in seminal antioxidants and
the lack of serious side effects related to antioxidant therapy.
Ideally, an oral antioxidant should reach high concentrations in
the reproductive tract and restore vital elements important for
spermatogenesis. Additionally, the antioxidant supplement should
augment the scavenging capacity of seminal plasma and reduce
levels of seminal ROS [15].
Oral treatment with antioxidants such as vitamins E, C, A,
B complex, coenzyme Q10 (CoQ10), ubiquinol, glutathione,
l-carnitine, lactoferrin, β-carotene, lycopene, pantothenic
acid, α-lipoic acid, N-acetyl-cysteine, selenium, zinc, copper or
supplements containing a combination of these antioxidants have
been used with success to varying degrees [16].
In infertile men, oral antioxidant therapy with Carni-Q-Nol
(440mg l-carnitine fumarate + 30mg ubiquinol+ 75 IU vitamin E
+ 12mg vitamin C) softules twice or thrice daily decreased sperm
pathology after 3 months, improved sperm density after 3 and 6
months, increased (ubiquinone + ubiquinol) & α-tocopherol and
decreased oxidative stress levels. Apart from improving sperm
parameters, the supplementary therapy with Carni-Q-Nol resulted
in a 45% pregnancy rate [17].
Moreover, antioxidant supplements are not free from potential
side effects “antioxidant paradox”. Further placebo-controlled,
dietary-controlled, double-blind, randomized-controlled,
prospective studies with standardized supplement regimens are
needed to elucidate the role of antioxidant therapy in the treatment
of oxidative stress and management of male infertility [7].
Antioxidants
Protective antioxidant system comprehends enzymatic factors
(superoxide dismutase (SOD), catalase and glutathione peroxidase
(GPX), non-enzymatic factorsand low molecular weight compounds
(glutathione, N-acetyl-cysteine (NAC), vitamins A, E & C, coenzyme
Q10 (CoQ10), carnitines, myoinositol (MYO), lycopene, astaxanthin,
Serenoa repens, etc.), and micronutrients (Selenium, Zinc, &
Copper) which interact each other to ensure an optimal protection
against the oxidative stress. A deficiency of one of them may result
in a decrease of total plasma antioxidant capacity [18]. The main
antioxidants will be discussed below.
Superoxide dismutases
SODs are metalloenzymes that convert superoxide to hydrogen
peroxide (H2O2) and comprehend two intracellular and one
extracellular forms. The intracellular form contains copper and zinc
in the active center (CuZnSOD). It is encoded by the SOD1 gene and
it is mainly localized in the cytoplasm. The other intracellular form
is manganese SOD (MnSOD) that acts in the mitochondrial matrix
[18]. Its gene, SOD2, is inducible under various inflammatory
conditions and the nuclear factor kappa B (NF-kB) appears to be the
main factor responsible for its induction. Homozygous SOD2 gene-
deficient mice have severe cardiovascular damage and die soon
after birth. No abnormality in the genital tract has been reported
in these mice. On the contrary, transgenic male mice that express
higher levels of MnSOD are infertile. Since SOD only dismutates
superoxide anion into hydrogen peroxide, the resulting H2O2 may
also cause a toxic effect in testicular cells [19].
The extracellular form of SOD (ECSOD), encoded from SOD3
gene, can be present in a free form or can be connected to the
surface polysaccharides. It is structurally similar to the MnSOD,
but it has zinc and copper in the active center. It has been shown
that erectile function is improved by transferring the SOD3 gene to
the penis in aged rats. Scavenging superoxide increases nitric oxide
(NO) half-life that results in increased cGMP levels [19].
The main active isoenzymes in the seminal plasma are
CuZnSOD (75%) and ECSOD (25%) which probably originate from
the prostate [20]. SODs have been observed to play a role in the
protection of testicular cells against heat stress-induced apoptosis
both in vivo and in vitro [21]. Moreover, SOD activity has been lower
in infertile patients than in fertile controls and correlates positively
with sperm motility and morphology [22].
3. Surgical Medicine Open Access Journal
How to cite this article: Khaled Gadallah, Abeel A M.Role of Antioxidants in the Treatment of Male Infertility. Surg Med Open Acc J. 1(2).SMOAJ.000507. 2019. 3/10
Surg Med Open Acc J
Volume 1 - Issue - 2
Some in-vitro studies suggest that SODs may play a role
in improving sperm parameters in thawed semen samples.
In fact, supplementation with manganese (III) mesotetrakis
(N-ethylpyridinium-2-yl) porphyrin chloride (MnTE), a permeable
SOD mimetic agent, seems to improve total motility, membrane
integrity, and viability of goat semen samples after thawing,
the acrosomal integrity and the blastocyst formation rate [23].
However, since MnTE supplementation protects spermatozoa from
superoxide but not from H2O2, the degree of sperm parameters
improvement is higher when also catalase is simultaneously added
[24]. There are evidences for positive effects of the treatment with
SODs also on human spermatozoa. In fact, the supplementation
of exogenous SODs at the dose of 400U/mL to the human sperm
suspension prevented the loss of motility and the increase of MDA
concentration, thus showing a significant role of SODs for human
sperm motility. Actually, SOD is included in some over-the-counter
products that contain also other anti-antioxidants (e.g., D-chiro-
inositol, zinc, and folic acid), recommended for the treatment of
male infertility. There is a lack of studies investigating the effects
of SOD oral supplementation on human sperm. Hence, there is
not agreement about the dosage. However, the most common
therapeutic scheme suggested consists of an oral dosage of 150 UI a
day for at least three months [25].
Catalase
Catalase is a heme enzyme with a centrally located iron atom. It
catalyzes the decomposition of H2
O2
into molecular oxygen (O2
) and
water (H2
O). Its presence has been shown in the seminal plasma and
spermatozoa of both humans and rats. The extracellular enzyme is
produced by the prostate.
Under physiological conditions, catalase plays a role in the
nitric oxide-induced sperm capacitation [18]. Its activity has
been associated with low sperm quality [26]. In fact, H2O2, which
increases in case of catalase deficiency or reduced activity, plays a
substantial role on sperm motility due to the decrease in membrane
fluidity that is important for sperm-oocyte fusion [27]. It is not
commercially available.
Glutathione peroxidase
GPXs reduce hydrogen peroxide and organic peroxides,
including phospholipids, using the reduced form of glutathione
(GSH) as an electron donor [28]. GPXs protect sperm DNA from
oxidative damage, playing a role in the chromatin condensation and
mainly in the mitochondrial matrix [18]. GPX-defective expression
in human spermatozoa has been reported to be associated with
OAT [29].
GPXs are divided into two groups according to the presence of
seleno-cysteine in the enzyme isoform. Since, selenium deficiency
has been associated with male infertility, selenium-containing
GPXs are suspected to be a candidate for the defective molecule.
At least four isoenzymes belong to the selenium-containing GPX in
mammals.
GPX1 is a cytosolic isoform, widely distributed in tissues and,
like other antioxidant enzymes, and prevents apoptosis induced by
oxidative stress and other stimuli. GPX1 knockout mice do not show
reproductive abnormalities. GPX2 and GPX3 are gastrointestinal
and plasma isoforms, respectively.
GPX4 is highly expressed in testis and represents about the 50%
of the capsule material, which embeds the helix of mitochondria
in the midpiece of spermatozoa. GPX4 gene knockout mice show
premature embryonal death. The GPX4 gene encodes also for a
protein that has a high sequence identity to GPX4 except for the
N-terminal region. This protein is specifically present in sperm
nuclei and is considered to act as protamine thiol peroxidase.
GPX5 is a non-selenium enzyme. It is exclusively expressed in
the epididymis and secreted in the caput and caudal epididymal
lumen. It represents the 6% of the secretory epididymal proteins.
However, the activity of non-selenium dependent GPX in low and,
hence, its contribution as a GSH-dependent peroxide scavenger is
ambiguous [19]. However, neither catalase nor GPXs are currently
used for the treatment of male infertility.
Glutathione
Glutathione is a sulfur-containing tripeptide present in both
a reduced (GSH) and an oxidative (GSSG) states. GSH participates
in preserving the intracellular milieu in a reduced state and,
in addition, it is an electron donator to GPX. GSH displays its
antioxidant activity by the reconstruction of thiol groups (-SH) in
proteins and preventing cell membrane from lipid oxidation [18].
GSH levels are maintained through two metabolic pathways:
one is the de novo synthesis from Cys, Glu, and Gly that is catalyzed
by the γ-glutamyl-cysteine synthetase (GCS) and glutathione
synthetase; the other is its recycling by glutathione reductase,
using NADPH as an electron donor. Glutathione is pumped out
when it is oxidized or forms conjugates with cytotoxic compounds,
including xenobiotical chemicals. Plasma glutathione is hydrolyzed
γ-glutamyltranspeptidase (GGT), localized at the cellular surface as
a membrane protein, into its consisting amino acids that are then
taken up by the specific transporter and reused by cells [19].
In animals, GSH therapy affects positively sperm quality. It
has a crucial role in increasing sperm motility and fertilization in
bulls with asthenozoospermia due to varicocele and in rabbits with
dispermy caused by cryptorchidism [30].
Glutathione reduction in human seminal plasma leads to
instability of the midpieceof the spermatozoa, resulting in a motility
disorder [31]. Some authors suggested that its supplementation
plays a therapeutic role in some andrological diseases, particularly
during inflammation. Accordingly, its supplementation in infertile
men with unilateral varicocele or inflammation of the urogenital
tract (two conditions in which radical oxygen species or another
toxic compound production plays a pathogenetic function)
leads to a significant improvement of sperm parameters, such as
concentration, motility and morphology [32]. These effects on
spermatozoa can be partially reversed in case of not too severe
structural cell membrane damage [31], a prominent protective role
of GSH on the lipid components of the cell membrane [33].
4. How to cite this article: Khaled Gadallah, Abeel A M.Role of Antioxidants in the Treatment of Male Infertility. Surg Med Open Acc J. 1(2).SMOAJ.000507. 2019.
Surgical Medicine Open Access Journal
4/10
Surg Med Open Acc J
Volume 1 - Issue - 2
Glutathioneisgivenatthedosageof600mg/dayintramuscularly
for 2-3 months. Hence, glutathione is seldom prescribed for
male infertility. However, because of the route of administration,
the compliance is low and, currently, GSH is hardly used for the
treatment of male infertility.
N-Acetyl-Cysteine (NAC)
NAC is a glutathione precursor. NAC is effective in metal
chelation and it seems to improve sperm motility and to prevent
sperm DNA oxidative damage [18]. In an animal model, it is able to
improve sperm parameters and seminal vesicles weight, previously
altered by treatment with As2O3 [34]. Furthermore, it significantly
improves seminal fluid volume and viscosity and increase sperm
motility in humans [35]. In women suffering from polycystic ovary
syndrome, NAC (administered at the doses of 1500mg/day) has
been shown to ameliorate oocyte and embryo quality, representing
an alternative to metformin prescription [36]. Such findings
support the therapeutic use of this compound for the treatment of
human infertility.
The most common oral dosage used is 600mg/day. NAC
is commercialized in combination with other antioxidants. Its
administration is suggested for at least three months.
Vitamin A
Carotenoids are a group of fat-soluble organic compounds
found mainly in yellow, red, orange and pink vegetables. These
carotenoids are precursor of vitamin A. Retinal is formed from
them in the gastrointestinal tract, before being converted to retinol,
the most important component of vitamin A.
Carotenoidsarenaturalantioxidantsthatprotectcellmembrane
integrity, regulate epithelial cell proliferation, and are involved in
the regulation of spermatogenesis [18]. Moreover, in rats retinoids
have various effects on fetal and neonatal Sertoli, germ and Leydig
cell [37]. Carotenoid deficiency in the diet can lead to a reduction
in sperm motility [18]. Studies conducted on bulls have shown that
retinol might stabilize sperm acrosomal membrane when oxidative
stress increases because of the high temperature [38]. In humans,
lower serum retinol concentration has been correlated to a worse
sperm quality [39]. Hence, vitamin A administration could be a
therapeutic choice for the treatment of human male infertility. Not
many studies have evaluated the effects of vitamin A on human
sperm parameters. Currently, it is seldom added to the over-the-
counter preparation for male infertility treatment. However it
should be strengthening the concept that vitamin A has been shown
to be toxic and may be teratogenic in higher dose [40].
Vitamin C (Ascorbic Acid)
Vitamin C has a 10-fold higher concentration in seminal plasma
than in the serum [41]. It has a more powerful antioxidant action
when peroxyradicals are present in the aqueous phase [42] than
in the lipid membrane [43]. In mice, at a concentration equivalent
to the human therapeutic dose (10mg/Kg), it is able to reduce
MDA concentration, increasing sperm count and the proportion of
normal sperm population [44].
In humans, the seminal acid ascorbic levels correlate positively
with the percentage of morphologically normal spermatozoa
[45] and negatively with DNA fragmentation index [46]. This
finding supports the therapeutic use of vitamin C in infertile
males. At concentrations lower than 1000µmol/L, vitamin C is an
antioxidant; at higher concentrations it acts as a prooxidant agent
[47]. The dose of 1g/day provides a 2.2-fold increase in plasma acid
ascorbic concentrations [48]. The majority of the studies reported
in literature investigating the effect of vitamin C administration
on sperm quality refer to this orally administered dosage [49].
Accordingly, 1g daily vitamin C treatment improves human quality,
increasing mean sperm count, concentration, and motility [50]. The
duration of the treatment is not well established. There is evidence
for sperm parameters amelioration after one month of treatment
[51], but longer period of treatment is also reported [49]. The dose
of vitamin C must, however, is not excessive because high doses may
act as a prooxidant, particularly in persons with the haptoglobin
type 2-2 [52].
Vitamin E
Vitamin E (Tocopherol) is a fat-soluble organic compound
mainly localized in cell membranes. It protects sperm cell
membrane form oxidative stress-induced damage, preventing
lipid peroxidation and capturing free hydroxyl radicals and
superoxide [18]. Efforts have been made to establish if sperm
parameters could be improved by vitamin E supplementation [53].
Its seminal plasma concentration significantly increases when it
is administered at doses of 300 and 1200mg/day for three weeks
[54]. The -tocopherol concentration in spermatozoa is independent
from the total α-tocopherol concentration in seminal plasma, and it
significantly correlates with the percentage of motile spermatozoa
[55]. A double-blind placebo-controlled trial showed an improved
sperm function in vitro after 600mg daily administration of vitamin
E for three months. The administration resulted in improved sperm
motility and ability to bind the hamster oocyte in the hamster egg
penetration test [53]. In other studies, lower doses (200 or 300mg/
day) have been used [56].
A placebo-controlled double-blind study reported
an improvement of sperm motility in men with
oligoasthenoteratozoospermia after vitamin E oral
supplementation. The enhancement of sperm motility was
associated with a decreased sperm production of MDA, the end
product of the lipid peroxidation. Furthermore, in the course of
the six-month treatment period, 21% of patients belonging to
the treated group achieved pregnancy [57]. Seminal plasma MDA
decrease seems to correlate with the percentage of successful
attempts to achieve pregnancy. In a prospective study, 15
normozoospermic men with low fertilization rates in their earlier
ART cycles were treated with 200mg/day of vitamin E for three
months. The high MDA concentration declined to normal rate and
the fertilization rate per cycle significantly improved after one
month of treatment [56]. Finally, dietary habits seem also to play
a role in semen quality, since a positive correlation has been found
between vitamin E dietary intake and progressive and total motility
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[50]. This evidence suggests that vitamin E may have a positive
effect on semen quality, enhancing the pregnancy rate. Altogether,
these findings suggest that vitamin E could be a therapeutic choice
for the treatment of male infertility. However, we would emphasize
that, besides their interesting antioxidant properties, vitamin E
analogs, especially tocopheryl succinate, can exert adverse effects
on gap junctional intercellular communication, which could explain
their controversial effects in spermatogenesis [52].
Coenzyme Q10
CoQ10 is the only lipid soluble antioxidant synthesized
endogenously. In the Q-cycle it is present in three redox states:
ubiquinone (CoQ10-oxidized), ubiquinol (CoQ10H2-reduced) and
semiquinone (partially reduced, as radical). The reduced form
has a higher antioxidant effect and concentration in the body is
approximately 90% of total CoQ10. It inhibits protein and DNA
oxidationandlipidperoxidation.CoQ10regulatesthemitochondrial
electron transport in the respiratory chain, receiving electrons
from complex I and complex II and passing them to complex III, and
it transfers protons from fatty acids to the matrix. It also regulates
the permeability transition pore opening and nutrition uptake
through the voltage dependent anion channel (VDAC) of the outer
mitochondrial membrane [17].
A number of clinical studies documented the beneficial effects
of ubiquinone on male fertility. In fact, it has been shown to improve
sperm parameters (concentration, motility, and morphology) in
menwithidiopathicOAT[58],withpositiveeffectsonthepregnancy
rate [59]. It displays a protective effect against oxidative stress and
sperm DNA damage. In addition, CoQ10 treatment improves sperm
parameters and antioxidant status in infertile men with varicocele.
Different therapeutic schemes are reported in literature. The lower
dosage used is 90mg/day for a minimum of 3 months to a maximum
of 9 months, but positive effects on sperm parameters have been
obtained also by higher dosages (e.g., 100mg/day for three menses,
200mg for six months, etc.). The highest dosage reported is 300mg
twice a day for twelve months [17].
Ubiquinol has a stronger antioxidant action in comparison
with ubiquinone. It can regenerate other antioxidants such as
vitamin E and vitamin C. In addition, CoQ10 testicular biosynthesis
is very active and high levels of ubiquinol are present in sperm
[60]. Ubiquinol sperm concentration strongly correlates with
sperm count, motility, and morphology. In addition, Q10-total
concentration directly correlates with sperm motility [17].
Ubiquinol is administered orally at a dosage of 150 to 200mg daily,
for at least four months.
Carnitine-ubiquinol combination displays a beneficial effect
on sperm mitochondrial function of infertile men. It may be due to
their uptake by VDAC of the outer mitochondrial membrane, along
with the activity of carnitine palmitoyltransferase I (CPTI) in outer
mitochondrial membrane. However, further studies are required to
support this hypothesis [17].
Carnitine
Currently, carnitine is the molecule with antioxidant activity
that has the greatest consensus in literature, especially in its forms
L-carnitine and L-acetyl-carnitine. L-carnitine (mainly of exogenous
origin though human beings are able to synthesize) is a high-polar,
water-soluble quaternary amine. It acts as an essential cofactor for
the transport of long chain fatty acids within the mitochondrial
matrix in order to facilitate the oxidative processes and to enhance
cellular energy production [61]. L-acetyl-carnitine, instead, is
formedbytheenzymeacetyl-L-carnitinetransferasethatmodulates
the intracellular and mitochondrial concentration of coenzyme
A (CoA) and acetyl-CoA. Interestingly, high concentrations of
carnitine are present in the male reproductive tract and particularly
in the epididymis, suggesting its crucial role in energy metabolism
and sperm maturation [62]. Hence, carnitine concentration in the
ejaculate is considered a marker of epididymal function and some
studies have shown a decreased L-carnitine concentration in the
seminal fluid of patients with epididymitis [63].
The antioxidant properties of carnitine have been studied in
men with male accessory gland inflammation. As previously said,
inflammatory processes increase ROS production from leukocytes
and/or spermatozoa with a consequent increased oxidative stress.
Since, prostate-vesiculo-epididymitis (PVE) is the diagnostic
category with a higher level of oxidative stress, some studies have
evaluated the antioxidant properties of L-carnitine administration
in patients with microbial PVE. The results of these studies have
shown that the best effect is obtained administering first antibiotic
and anti-inflammatory drug and subsequently L-carnitine. The
co-administration of antimicrobial agents and antioxidants is less
effective while treatment with L-carnitine alone has no effect [64].
The beneficial effects of L-carnitine on sperm parameters
are well known. The data in the literature show a statistically
significant improvement of sperm progressive motility in patients
with OAT treated with L-carnitine or acetyl-L-carnitine at the dose
of 3g/day [65] for some months. Moreover, treatment with acetyl-
L-carnitine increases sperm motility and viability in asymptomatic
infertile patients with ROS overproduction and ultrasonographic
evidence of PVE who already received antimicrobial therapy
[62]. However, despite improving sperm parameters, there is
no evidence of statistical significant variation of seminal plasma
α-glycosidase concentration (a marker of epididymal function) and
of sperm membrane lipid peroxidation [66]. Combination therapy
with L-carnitine (2g/day) and acetyl-L-carnitine (500mg twice a
day) is also effective in improving sperm quality in infertile patients
(Lenzi et al., 2004) [66,67] and it improves the total oxyradical
scavenging capacity of the seminal fluid [68] and sperm parameters
[68]. Interestingly, the addition of L-carnitine in samples to be
cryopreservation improves significantly sperm quality [70].
In conclusion, the administration of carnitines is a rational and
effective therapeutic strategy for the treatment of male infertility,
since it leads to an improvement in sperm parameters. The best
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therapeutic scheme is represented by the co-administration of
at least 2g/daily of L-carnitine and at least 1g/daily of acetyl-L-
carnitine for at least three months.
Myoinositol
Inositol is a component of the vitamin B complex. MYO, the
most biologically important form in nature, is a precursor of
second messengers and it is involved in several signal transduction
mechanisms in the cell membrane. It regulates seminal plasma
osmolarity, the expression of proteins essential for embryogenetic
development and for sperm chemiotaxis and sperm motility. In
addition, inositols are involved in sperm capacitation and acrosome
reaction.
Incubation with MYO results in an increased sperm motility
and in a higher number of spermatozoa retrieved by swim-up in
both normozoospermic men and in patients with abnormal sperm
parameters. This was associated with an improvement of sperm
mitochondrial function in patients with OAT [71]. On this basis,
the therapeutic use of MYO has been suggested in both in vivo
and in vitro assisted reproductive techniques. Accordingly, oral
supplementation with MYO seems to improve sperm parameters
[72]. In particular, a double-blind, randomized, placebo-controlled
study showed that patients with idiopathic infertility, treated for
three months with MYO (2g twice daily), had a significant increase
of sperm concentration, total count, progressive motility, and
acrosome-reacted spermatozoa. In addition, MYO rebalances LH,
FSH, and inhibin-B concentrations [73].
The most frequently reported supplementation strategy
consists of a daily oral dose of 4g (plus 400µg of folic acid), for at
least two months.
Lycopene
Lycopene is a constituent of the human redox protection
mechanism against ROS. Although few studies investigated its
effects on sperm parameters, it seems to be a therapeutic choice
in the treatment of idiopathic male infertility. In facts, its oral
administration (2g twice a day for 3 months) improved sperm
concentration and motility [74]. Furthermore, lycopene displays a
protective effect against cryopreservation injury of post-thawing
human spermatozoa. In fact, the addition of lycopene at a proper
concentration to cryo-protectant reduces oxidative damage to
sperm mitochondria in the freezing-thawing process, attenuates
oxidative stress injury induced by ROS to sperm plasma membrane,
and improves the anti-apoptosis sperm ability [75]. Various
lycopene supplementation studies conducted on both humans and
animals have shown promising results in alleviating male infertility
by decreasing lipid peroxidation and DNA damage and increasing
sperm count and viability. Improvement of these parameters
indicates a reduction of the oxidative stress, and thus spermatozoa
were less vulnerable to oxidative damage, which increases the
chances of a normal sperm fertilizing the egg. Human trials have
reported sperm parameter improvement and pregnancy rates
with supplementation of 4-8mg of lycopene daily for 3-12 months.
However, further detailed and extensive research is still required
to determine the dosage and the usefulness of lycopene for male
infertility treatment [76].
Astaxanthin
Astaxanthin is natural occurring xanthophyll. Only one study
described its effects on human male fertility. A supplementation
with 16mg daily of astaxanthin in 30 infertile patients resulted in
higher sperm linear velocity, better capacity of binding the oocyte
in the hamster penetration test, and higher total and per cycle
pregnancy rates compared to the placebo group [77]. In a model
of obese rats, vitamins A and E and astaxanthin administration
was associated with better viability, motility, and morphology of
spermatozoa obtained from the tail of the epididymis and with
a significantly higher number of spermatogonium and Sertoli
cells at the histological evaluation [78]. This finding led to the
hypothesis that low sperm quality of obese men may be improved
by the administration of this cocktail of antioxidants. However,
other studies on a greater number of patients are needed to
confirm if human sperm parameters may benefit from astaxanthin
administration. Astaxanthin is administered in combined therapies
at a daily dose of 16mg. The duration of the treatment is not
defined; in the mentioned study, astaxanthin was administered for
three months [77].
Serenoa repens
Serenoa repens (saw palmetto) is a natural product with
anti-inflammatory properties, derived from the American dwarf
palm [79]. Currently, it is used to treat inflammatory symptoms in
patients with benign prostatic hyperplasia and chronic prostatic
inflammation [80]. Up to now, only a few and old studies have
investigated its effects on sperm parameters. According to Ondrizek
and colleagues, high concentration of Serenoa repens, Echinacea,
or ginkgo inhibits human sperm motility. Moreover, Serenoa repens
does not have any effect on oocyte penetration and sperm DNA
integrity, while other herbs (such as Echinacea purpurea, Ginkgo
biloba, and Hypericumperforatum) damage these parameters [81].
On this basis, Serenoa repens does not seem to ameliorate sperm
parameters. Further studies are needed to confirm this conclusion.
Micronutrients
The concentration of micronutrients such as selenium, zinc and
copper correlates with human sperm quality [18].
Selenium: Selenium is a micronutrient essential for normal
testicular development, spermatogenesis, sperm motility and
function. The lack of selenium has been correlated to seminiferous
epithelium atrophy, disorders of spermatogenesis, maturation of
spermatozoa in the epididymis, testis volume reduction, decreased
sperm motility and altered sperm morphology (mainly in the head
and in the midpiece) [82]. The exact mechanism by which selenium
reduces oxidative stress and improves sperm parameters is still
controversial. Its action seems to be mediated by seleno-enzymes,
such as GPXs [83]. Selenium is given orally at a dosage that ranges
from (80 to 300µg) once a day, alone or in combination with
antioxidants, for at least 3 months.
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Zinc: Zinc is a component of over 200 enzymes involved in
the biosynthesis of nuclear acids, proteins and the process of cell
division [18]. It has been reported to normalize oxido-sensitive
indices and catalase-like activity in the seminal fluid of astheno-
zoospermic patients [84].
Zinc is given orally at the dose of (220mg) once or twice a day
for 3 to 4 months, alone or in addition to folic acid (5mg daily).
In combined therapies, it is administered at the dose of at least
10mg a day. It should be given in the esterified formulation as zinc
picolinate that is best taken up by the intestinal tract [85].
Copper: Copper is a trace element whose seminal plasma
concentration correlates with sperm quality [18]. A few studies
report a positive effect of copper supplementation on sperm
parameters in animals. In vitro supplementation with copper on
ejaculated buffalo sperm led to a better protection through the
process of dilution, equilibration and freeze-thawing at the dose
of 32µg/L compared to the dosage of 64µg/L [86]. In addition,
dietary copper supplementation at a dosage of 110mg/kg has been
shown to prevent the adverse effects produced by 12mg/kg/day
of tetrathiomolybdate in rat spermatozoa [87]. No studies have
explored the effects of copper supplementation on human sperm
parameters. Copper is not prescribed for the treatment of male
infertility.
Combined therapies
The synergic effect of some component with different
antioxidant properties has been studied. In a randomized trial, the
dailyadministration ofvitamin E (400mg)andselenium(225µg)for
3 months resulted in a significant decrease in MDA concentrations
and an improvement of sperm motility [27]. In mice, the co-
administration of vitamin C (10mg/kg) and vitamin E (100mg/kg)
led to a decrease of testicular MDA content, along with increased
sperm count and decreased percentage of spermatozoa with
abnormal form [44]. According to Greco and colleagues, the daily
administration of vitamin C (1g) and vitamin E (1g) for 2 months
significantly decreased the percentage of human DNA-fragmented
spermatozoa. In addition, this association led to an improvement
in the clinical pregnancy and implantation rates compared to the
group of patients receiving placebo [88]. Furthermore, there is
evidence for an increase of seminal vitamin E concentration and
of its oxidative stability after cryopreservation if high amount of
dietary -tocopheryl acetate is consumed. A decrease of seminal
plasma ascorbate concentration is associated with a decreased
fertilization rate. In rabbits, a high amount of dietary vitamin E (50
versus 200mg/kg diet) significantly increased the level of vitamin E
in the seminal fluid and the sperm oxidative stability after storage
at 5 °C for 24h.
Ascorbic acid showed a different effect in relation to the vitamin
E status of animals: when associated with the higher level of vitamin
E it increased vitamin E and the semen oxidative stability, whereas
both parameters were reduced with lower vitamin E levels. Hence,
theircombinationsignificantlyimprovestheviabilityandkineticsof
spermatozoa with an increased fertility rate [89]. These evidences
sustain the role of the co-administration of vitamins E and C for the
improvement of sperm quality in idiopathic male infertility.
The use of NAC, vitamin A, vitamin E and essential fatty acids
in 27 infertile males increases sperm count and decreases ROS
and 8-hydroxydeoxyguanine concentration in oligo-zoospermic
patients. Moreover, the treatment improved the acrosome reaction
rate and the proportion of PUFA in phospholipids and sperm
membrane [85]. In addition, a 26-week-long daily administration
of selenium (200µg) and NAC (600mg) in 468 infertile men with
idiopathic astheno-zoospermia resulted in an improvement of all
sperm parameters. Furthermore, a positive relationship between
seminal plasma concentration of NAC and selenium and sperm
parameters has been found [90].
Other treatment
Pine bark extract: The extract of the bark of the
(Mediterranean) pine tree, Pinusmaritima, is rich in polyphenols,
namely, anthocyanidins with antioxidant effect, and it reduces
inflammatory reaction through the inhibition of the Cyclooxygenase
enzymes (COX: 1 & 2) [85] and of the Nuclear Factor Kappa B (NF-
kB). Its potential use can be of interest in order to counteract sperm
oxidative stress.
Lepidiummeyenii: Lepidiummeyenii, also called maca, is
another plant belonging to the cruciferous (Brassica) family,
growing in the Peruvian Andes Mountains. It has been considered
phytoadaptogen that increases the production of the Heat Shock
Protein (P 72), by reducing the negative impact of stress on
protein conformation and cell death [85]. Moreover, the potential
increase of sexual desire induced by this plant without influencing
testosterone concentration in adult men could be of importance for
male infertility.
Polyunsaturated fatty acids: Polyunsaturated fatty acids have
been recommended for nutrition thanks to their several benefits. In
fact these fatty acids improve cell membrane fluidity and function,
may possibly protect against cardiovascular diseases, and regarding
male infertility may be potentially useful for the spermatogenesis
[40].
Summary
The identification of etiopathogenetic mechanism(s) allows
clinicians to select the optimal treatment to overcome male
infertility. The therapeutic repertoire includes antibiotics, anti-
inflammatory drugs, antioxidants and micronutrients. Antibiotics
are prescribed when a urogenital infection is identified. The most
used antibiotics in clinical practice are quinolones (ciprofloxacin,
levofloxacin, etc.), tetracyclines, macrolides, trimethoprim and
β-lactam antibiotics (penicillin derivatives, cephalosporins,
monobactams and carbapenems). Anti-inflammatory drugs should
be given when leukocytospermia and/or inflammatory sign and/
or symptoms are present. Finally, antioxidants and micronutrients
may be used to protect spermatozoa from oxidative stress
overproduction that occurs in many clinical conditions. This class
includes a vast array of molecules that may be prescribed alone or
in combination.
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In conclusion, many non-hormonal compounds are available
for the treatment of the infertile patient. This allows a customized
therapeutic strategy.
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