This document provides an overview of corticosteroid-induced disorders and adverse effects. It discusses the mechanism of action of corticosteroids and their effects on muscle, including causing muscle atrophy primarily through increased protein breakdown and inhibition of protein synthesis. It also mentions other corticosteroid-induced disorders like osteoporosis, glaucoma, diabetes, psychosis, and Cushing's syndrome. Prevention of corticosteroid-induced muscle atrophy through growth factors, amino acids, glutamine, taurine, and creatine is also summarized.
This study investigated protein breakdown in skeletal muscles of diabetic rats. The researchers found:
1) Muscle extracts from diabetic rats contained greater amounts of ubiquitinated proteins and had 40-50% higher rates of ubiquitin conjugation compared to controls.
2) The increased ubiquitination in diabetic muscles occurred mainly through the N-end rule pathway involving E2 14k and E3α enzymes.
3) mRNA levels of E2 14k and E3α were elevated 2-fold in diabetic muscles, although protein levels were not significantly changed.
4) The results suggest that small increases in both E2 14k and E3α enzymes in diabetic muscles accelerates ubiquitin conjugation and protein breakdown
L'idrossitirosolo è in grado di proteggere e aumentare l'attività dei mitocon...CreAgri Europe
L'idrossitirosolo, un polifenolo estratto dalle olive, attraverso una protezione dei mitocondri, le centrali energetiche della cellula, è in grado di aumentare la resistenza muscolare negli animali da esperimento
1) The document discusses recent research on the regulation of human skeletal muscle protein metabolism by exercise, amino acids, and aging.
2) It finds that resistance exercise increases muscle protein synthesis through activating mTORC1 signaling pathways, and that blood flow restriction exercise can provide similar benefits to high intensity resistance exercise.
3) Aging is associated with an impaired ability of muscle to respond to anabolic stimuli like resistance exercise, but blood flow restriction exercise may help overcome this impairment in older adults.
4) Essential amino acid ingestion, especially leucine, can stimulate muscle protein synthesis through mTORC1 signaling, and combining amino acids with resistance exercise enhances this response.
This fourth edition continues to integrate the science and practice of sports nutrition. Each chapter is specifically formatted to combine the viewpoints of two sports nutrition experts: the scientific principles underpinning each issue are reviewed by an internationally recognized nutritionist with extensive research experience, while a sports dietitian summarizes the practice tips that can be drawn from these principles. Topics include the measurement of the nutritional status of athletes, assessing the physique of the athlete, weight loss and making weight, fluid and carbohydrate intake during exercise, supplements and sports foods, requirements for special athletic populations (i.e. diabetics and vegetarians), and the prevention, protection, and treatment of iron deficiency and depletion.
The document discusses how removing cholesterol from cells using methyl-beta cyclodextrin can impact muscle contraction. Preliminary studies showed it induced fruit fly muscle contractions. The author then examined its effects on crayfish hindgut muscles, finding it consistently increased the amplitude of spontaneous contractions in both whole hindguts and isolated longitudinal muscle strips, though its ability to change contraction frequency or duration was inconsistent. The results support the role of cholesterol in regulating muscle function.
This document summarizes research on creatine as an ergogenic aid. It discusses how creatine occurs naturally and helps supply energy to cells, especially muscle cells. It reviews studies showing that creatine supplementation can benefit performance in short, powerful activities by increasing ATP and PCr levels but may not improve endurance. The document also examines creatine synthesis and transport in the body, the roles of creatine and PCr in energy production and muscle contraction, and the effects of creatine on muscle fiber type, age, and training status.
Cre recombinase expression in cardiomyocytes using the αMHC-MerCreMer mouse model induces dose-dependent cardiac toxicity and lethality when higher doses of tamoxifen are used to increase recombination efficiency. Moderate and high tamoxifen doses caused heart failure and death in the mice through a DNA damage response leading to cardiomyocyte apoptosis and fibrosis. Lower tamoxifen doses achieved near maximal 80% recombination rates without toxicity. The optimal dose for recombination while minimizing effects was determined to be 30 μg tamoxifen/g body weight injected over three days. The study provides insights into the cellular mechanisms of cardiac Cre toxicity and an improved protocol for the αMHC-MerCreMer system.
Nutritional immunology is a fascinating but highly complex and conflicted subject area. With almost every nutrient we consume having the ability to affect our immune response in one way or another and the activation of the immune system dramatically increasing nutrient requirements, understanding the genetic, cellular and metabolic mechanisms that interact, control and conflict with the immune system and how to manipulate them to our advantage, is fundamental to optimal health.
We are thrilled to announce that we have linked up with Professor Phillip Calder, a world renowned and highly cited expert in nutritional immunology, with over 500 publications to his name. Professor Calder will be joining us as our guest speaker for our January Webinar to help us kick off what promises to be our most exciting year of clinical nutrition education yet.
In this detailed Q&A session Professor Calder will shed light on a whole host of fascinating topics from the latest research into nutrition immunology, his projects involving nutrigenomics, probiotics and omega-3s, the real science behind effective clinical omega-3 interventions, his thoughts on the best forms of lipid supplementation, and doing some serious nutrition science myth busting.
This study investigated protein breakdown in skeletal muscles of diabetic rats. The researchers found:
1) Muscle extracts from diabetic rats contained greater amounts of ubiquitinated proteins and had 40-50% higher rates of ubiquitin conjugation compared to controls.
2) The increased ubiquitination in diabetic muscles occurred mainly through the N-end rule pathway involving E2 14k and E3α enzymes.
3) mRNA levels of E2 14k and E3α were elevated 2-fold in diabetic muscles, although protein levels were not significantly changed.
4) The results suggest that small increases in both E2 14k and E3α enzymes in diabetic muscles accelerates ubiquitin conjugation and protein breakdown
L'idrossitirosolo è in grado di proteggere e aumentare l'attività dei mitocon...CreAgri Europe
L'idrossitirosolo, un polifenolo estratto dalle olive, attraverso una protezione dei mitocondri, le centrali energetiche della cellula, è in grado di aumentare la resistenza muscolare negli animali da esperimento
1) The document discusses recent research on the regulation of human skeletal muscle protein metabolism by exercise, amino acids, and aging.
2) It finds that resistance exercise increases muscle protein synthesis through activating mTORC1 signaling pathways, and that blood flow restriction exercise can provide similar benefits to high intensity resistance exercise.
3) Aging is associated with an impaired ability of muscle to respond to anabolic stimuli like resistance exercise, but blood flow restriction exercise may help overcome this impairment in older adults.
4) Essential amino acid ingestion, especially leucine, can stimulate muscle protein synthesis through mTORC1 signaling, and combining amino acids with resistance exercise enhances this response.
This fourth edition continues to integrate the science and practice of sports nutrition. Each chapter is specifically formatted to combine the viewpoints of two sports nutrition experts: the scientific principles underpinning each issue are reviewed by an internationally recognized nutritionist with extensive research experience, while a sports dietitian summarizes the practice tips that can be drawn from these principles. Topics include the measurement of the nutritional status of athletes, assessing the physique of the athlete, weight loss and making weight, fluid and carbohydrate intake during exercise, supplements and sports foods, requirements for special athletic populations (i.e. diabetics and vegetarians), and the prevention, protection, and treatment of iron deficiency and depletion.
The document discusses how removing cholesterol from cells using methyl-beta cyclodextrin can impact muscle contraction. Preliminary studies showed it induced fruit fly muscle contractions. The author then examined its effects on crayfish hindgut muscles, finding it consistently increased the amplitude of spontaneous contractions in both whole hindguts and isolated longitudinal muscle strips, though its ability to change contraction frequency or duration was inconsistent. The results support the role of cholesterol in regulating muscle function.
This document summarizes research on creatine as an ergogenic aid. It discusses how creatine occurs naturally and helps supply energy to cells, especially muscle cells. It reviews studies showing that creatine supplementation can benefit performance in short, powerful activities by increasing ATP and PCr levels but may not improve endurance. The document also examines creatine synthesis and transport in the body, the roles of creatine and PCr in energy production and muscle contraction, and the effects of creatine on muscle fiber type, age, and training status.
Cre recombinase expression in cardiomyocytes using the αMHC-MerCreMer mouse model induces dose-dependent cardiac toxicity and lethality when higher doses of tamoxifen are used to increase recombination efficiency. Moderate and high tamoxifen doses caused heart failure and death in the mice through a DNA damage response leading to cardiomyocyte apoptosis and fibrosis. Lower tamoxifen doses achieved near maximal 80% recombination rates without toxicity. The optimal dose for recombination while minimizing effects was determined to be 30 μg tamoxifen/g body weight injected over three days. The study provides insights into the cellular mechanisms of cardiac Cre toxicity and an improved protocol for the αMHC-MerCreMer system.
Nutritional immunology is a fascinating but highly complex and conflicted subject area. With almost every nutrient we consume having the ability to affect our immune response in one way or another and the activation of the immune system dramatically increasing nutrient requirements, understanding the genetic, cellular and metabolic mechanisms that interact, control and conflict with the immune system and how to manipulate them to our advantage, is fundamental to optimal health.
We are thrilled to announce that we have linked up with Professor Phillip Calder, a world renowned and highly cited expert in nutritional immunology, with over 500 publications to his name. Professor Calder will be joining us as our guest speaker for our January Webinar to help us kick off what promises to be our most exciting year of clinical nutrition education yet.
In this detailed Q&A session Professor Calder will shed light on a whole host of fascinating topics from the latest research into nutrition immunology, his projects involving nutrigenomics, probiotics and omega-3s, the real science behind effective clinical omega-3 interventions, his thoughts on the best forms of lipid supplementation, and doing some serious nutrition science myth busting.
Around 250,000 people in the UK are currently thought to be affected by CFS/ME. The high level of disability that is often associated with this debilitating condition can be both physically and mentally challenging for patients and appears to stem from a combination of symptoms such as fatigue, pain, sleep disturbance, cognitive impairment, depression and, in many cases, symptoms mirroring those of irritable bowel syndrome.
With no current cure and no validated, universally accepted, ‘one-size-fits-all’ approach to the treatment, many clients are seeking natural alternatives to conventional approaches.
Taking a personalised and functional medicine approach, Dr Nina Bailey reviews the latest science on ME/CFS and the underlying mechanisms that can be targeted with nutritional interventions and explains how to ensure your therapeutic approach is right for your clients.
Covered in the webinar:
1. CFS/ME background /causes/symptoms
2. Update on the mechanisms associated with CFS/ME:
- Immune disturbances
- Oxidative stress and inflammation
- The kynurenine pathway and neurotransmitter dysregulation
- Mitochondrial dysfunction and related mechanisms
* Methylation
* Detoxification
* Glycolysis
* Citric acid cycle/Krebs
* Oxidative phosphorylation
3. An overview of current treatment options
4. Nutritional intervention – an evidence-based approach
5. Nutritional supplementation
This document discusses glycine, an amino acid that has anti-inflammatory properties and may be conditionally essential for humans. It covers glycine's role in collagen production, metabolic syndrome, stroke, and other diseases. Studies show glycine supplementation can reduce inflammation and improve metabolic markers in people with conditions like metabolic syndrome and diabetes. Animal studies also indicate glycine's protective effects against liver damage, cancer, and other issues. Dietary sources of glycine include collagen, gelatin, bone broth, and magnesium glycinate.
The document discusses supplements that can improve immune function before, during, and after workouts. Key supplements mentioned include beta-androstenetriol, phosphatidylserine, nucleotides, complex carbohydrates, whey protein/L-glutamine, L-citrulline malate, N-acetyl cysteine, and branched chain amino acids. These supplements are said to reduce cortisol and inflammation, boost Th1 cytokines, and enhance cell-mediated immunity and recovery. Post-workout, the author recommends more beta-androstenetriol, whey protein, L-glutamine, L-citrulline, fish oil, and apple to further support immunity and recovery.
Fatty acids carry out many functions that are necessary for maintaining optimal health, and the fatty acid status of a client provides valuable information that relates to both risk and progression of a range of diseases. Determining fatty acid status assists the practitioner in identifying those individuals who would benefit from omega-3 supplementation. The Igennus Opti-O-3 biomarker test is a safe, cost effective and minimally invasive dried blood spot (DBS) method that can be carried out by the client at home. In addition, the Opti-O-3 offers a personalised approach to condition management by focusing on optimising validated biomarkers of disease risk through identification of the client’s unique fatty acid requirements.
In this refresher webinar, Dr Bailey will discuss:
- Fatty acid testing: who, why and when?
- Why choose the Igennus Opti-O-3: a comparison of laboratories
- How to interpret results, including:
- New fatty acid reference ranges
- Overview of fatty acid functions
- Intervention considerations
- Personalised intervention
1) Overexpression of microRNA-146a (miR-146a) in myeloid cells decreases osteoclast differentiation and bone erosion in rheumatoid arthritis (RA) by targeting TRAF6 and IRAK1 proteins critical for osteoclastogenesis.
2) The researcher aims to evaluate the effects of overexpressing miR-146a specifically in myeloid cells in a mouse model of RA induced by mBSA and IL-1β injections using a genetic mouse model that allows tamoxifen-inducible overexpression of miR-146a in myeloid cells.
3) The researcher hypothesizes that overexpressing miR-146a in myeloid cells prior to RA induction will decrease osteocl
This document summarizes a presentation on managing chronic inflammation through modulating fatty acids like omega-3 and arachidonic acid. It discusses how inflammation contributes to diseases like cancer and dementia, and how biomarkers like the omega-3 index, omega-6/omega-3 ratio, and AA/EPA ratio can be used to personalize omega-3 dosing to reduce inflammation. Clinical evidence suggests EPA in particular may help treat inflammation and inhibit cancer progression by competing with arachidonic acid metabolism.
This document reviews the role of reactive oxygen species (ROS) in muscle function and how they may contribute to age-related sarcopenia. ROS are produced in muscles through various pathways including the mitochondrial electron transport chain and NADPH oxidase enzymes. At low levels, ROS play a role in muscle force production and exercise adaptation, but high levels can damage muscles. In aging muscles, ROS levels increase due to reduced antioxidant defenses and may cause cumulative oxidative damage, contributing to sarcopenia through impaired muscle mass, strength, and function.
Exercise metabolism and the molecular regulation of skeletal muscle adaptationviniufrrj
Tthis is a review of the metabolic responses and molecular mechanisms that underpin the adaptatation of skeletal muscle to acute exercise and exercise training.
This document summarizes research on the effects of exercise on gene expression of inflammatory markers in human peripheral blood cells. It reviews 37 studies that examined gene expression in white blood cells like lymphocytes and monocytes after acute and long-term exercise. The studies found that an acute bout of exercise can upregulate expression of some pro-inflammatory genes like IL-1β, IL-8 and CXCL16 in peripheral blood mononuclear cells. However, long-term regular exercise is associated with attenuated inflammatory response and upregulation of anti-inflammatory genes like IL-10 and IL-13. Gene expression changes depend on exercise duration and intensity. The immune system and inflammatory response play a role in diseases like cardiovascular disease and cancer, so understanding
Vladimir Heiskanen - Glycine: The Versatile Anti-inflammatory Nutrient (1st v...Vladimir Heiskanen
This document provides an overview of glycine, an amino acid that can have anti-inflammatory effects. It discusses how glycine may be conditionally essential for humans. Studies show glycine can help prevent metabolic syndrome by reducing inflammation caused by sugar, fat, and alcohol intake. Glycine also appears to protect against stroke and shows benefits for diseases like diabetes, cancer, and liver damage in animal studies. High-dose glycine supplements have helped with conditions like schizophrenia in humans. Dietary sources of glycine include collagen supplements, bone broth, and meat.
Grape Seed Extract : A potential Cancer suppressing agent sudharani028
Natural Polyphenol "Resveratrol" present predominantly in the grape seed plays an very important role in the treatment of devastating disorder Cancer (diseases involving abnormal and uncontrolled growth of cell with the potential to spread to other parts of the body)
This study examines how oxidized phospholipids interact with and activate certain ADAM and ADAMTS proteins in endothelial cells, contributing to inflammation in atherosclerosis. The study finds that oxidized PAPC (Ox-PAPC) activates the enzymatic activities of ADAMTS1 and ADAMTS4, which are involved in regulating the inflammatory chemokine IL-8. Ox-PAPC is shown to covalently bind to ADAMTS1 and ADAMTS4, and promotes cleavage of ADAMTS4 into its mature, active form. This binding and activation of ADAMTS proteins by Ox-PAPC may be one mechanism by which Ox-PAPC induces IL-8 expression
An analysis of metabolic fluxes in contracting human muscleGreg Crowther
This document summarizes research on analyzing metabolic fluxes in human muscle using phosphorus NMR spectroscopy. It discusses:
1. Why studying cellular metabolism in muscle is important, as it can provide insights into whole-body health and lead to medical advances.
2. How phosphorus NMR spectroscopy combined with force measurements can quantify metabolic fluxes non-invasively in vivo by monitoring changes in phosphocreatine and pH levels.
3. Findings that both elevated metabolite levels and a muscle activation factor like calcium are needed to initiate and sustain high glycolysis rates in muscle.
Intermittent fasting and metabolic syndromefathi neana
Dr. Fathi Neana discusses metabolic syndrome and its impact on the musculoskeletal system. Metabolic syndrome is reaching epidemic proportions and is associated with obesity, diabetes, gout, and other conditions that can cause surgical difficulties and complications. Intermittent fasting is presented as a potential strategy for correcting metabolic abnormalities and managing conditions associated with metabolic syndrome like type 2 diabetes.
This study investigated the effects of reducing Fsp27 (fat-specific protein 27) levels through antisense oligonucleotides (ASOs) in mouse models of obesity and insulin resistance. Mice fed a high-fat diet or leptin-deficient ob/ob mice were treated with Fsp27 ASOs. Partial reduction of Fsp27 resulted in decreased visceral fat, improved insulin sensitivity and blood glucose control, and changes in genes related to lipid metabolism. The results suggest that reducing FSP27 activity through ASOs could be a potential therapeutic approach for insulin resistance and obesity in patients.
In this brief review, neuromuscular adaptations to different forms of exercise are reviewed, the positive training effects of eccentric exercise are presented, and the implications for training are considered.
Nutrition is a key factor in the onset and progression of cognitive decline, yet despite a growing pool of research, little evidence exists to support the efficacy of single nutrients in this complex area. The most promising evidence comes from specific dietary patterns and nutrients in the prevention and slowed progression of neurodegenerative disease. During this webinar, Dr Bailey will focus on the synergistic role of key nutrients involved in the mechanisms that drive cognitive decline and support healthy brain aging. Topics include:
- Risk factors for cognitive decline
- Biological mechanisms underpinning cognitive decline
Dietary patterns that offer protection and support against cognitive decline
- The role of specific nutrients in protecting brain health and function
- Nutritional recommendations for healthy brain ageing
1) Timothy Sveeggen conducted mutagenesis experiments on the Mms6 protein, which is involved in iron manipulation in magnetotactic bacteria. He generated two double mutants, S119A/S122A and S119A/E124A, predicted to inhibit the protein's reductase activity.
2) Assays found that the S119A/S122A mutant completely lacked reductase activity, while the S119A/E124A mutant showed mixed results, possibly due to sample precipitation.
3) The study provides insight into Mms6's mechanism of iron reduction and how mutations affect this activity, furthering understanding of biological iron manipulation at the molecular level.
Alina Wilkinson Chem 499 Poster fall 2015(final revision)Alina Wilkinson
This document summarizes a study that compares the effectiveness, mechanism of action, and side effects of nine common NSAID drugs. It finds that NSAIDs work by inhibiting the COX-1 and COX-2 enzymes involved in prostaglandin production, which reduces inflammation, pain, and fever. Certain NSAIDs like ibuprofen, aspirin, and oxaproxin strongly inhibit COX-1, while naproxen sodium, celecoxib, sulindac, etodolac, and diclofenac strongly inhibit COX-2. Acetaminophen is unique in that it does not inhibit either enzyme. All NSAIDs carry side effects like upset stomach, headaches, and rashes
This document discusses potential biomarkers for cancer risk based on estrogen metabolism. It describes how estrogens like estrone and estradiol are metabolized into catechol estrogens that can form quinones and react with DNA. Specific estrogen metabolites, conjugates, and DNA adducts are proposed as possible early biomarkers for breast, prostate, and other cancers. Methods for analyzing estrogens and their metabolites in tissues and blood are also reviewed, with some studies finding higher levels of certain metabolites in cancer patients.
The human papillomavirus (HPV) family consists of over 150 virus types classified into genera based on DNA sequence homology, with the alpha genus containing mucosal HPV types divided into high-risk and low-risk groups depending on their ability to cause cancer, in particular certain high-risk alpha HPV types are established causes of cervical and head/neck cancers.
Around 250,000 people in the UK are currently thought to be affected by CFS/ME. The high level of disability that is often associated with this debilitating condition can be both physically and mentally challenging for patients and appears to stem from a combination of symptoms such as fatigue, pain, sleep disturbance, cognitive impairment, depression and, in many cases, symptoms mirroring those of irritable bowel syndrome.
With no current cure and no validated, universally accepted, ‘one-size-fits-all’ approach to the treatment, many clients are seeking natural alternatives to conventional approaches.
Taking a personalised and functional medicine approach, Dr Nina Bailey reviews the latest science on ME/CFS and the underlying mechanisms that can be targeted with nutritional interventions and explains how to ensure your therapeutic approach is right for your clients.
Covered in the webinar:
1. CFS/ME background /causes/symptoms
2. Update on the mechanisms associated with CFS/ME:
- Immune disturbances
- Oxidative stress and inflammation
- The kynurenine pathway and neurotransmitter dysregulation
- Mitochondrial dysfunction and related mechanisms
* Methylation
* Detoxification
* Glycolysis
* Citric acid cycle/Krebs
* Oxidative phosphorylation
3. An overview of current treatment options
4. Nutritional intervention – an evidence-based approach
5. Nutritional supplementation
This document discusses glycine, an amino acid that has anti-inflammatory properties and may be conditionally essential for humans. It covers glycine's role in collagen production, metabolic syndrome, stroke, and other diseases. Studies show glycine supplementation can reduce inflammation and improve metabolic markers in people with conditions like metabolic syndrome and diabetes. Animal studies also indicate glycine's protective effects against liver damage, cancer, and other issues. Dietary sources of glycine include collagen, gelatin, bone broth, and magnesium glycinate.
The document discusses supplements that can improve immune function before, during, and after workouts. Key supplements mentioned include beta-androstenetriol, phosphatidylserine, nucleotides, complex carbohydrates, whey protein/L-glutamine, L-citrulline malate, N-acetyl cysteine, and branched chain amino acids. These supplements are said to reduce cortisol and inflammation, boost Th1 cytokines, and enhance cell-mediated immunity and recovery. Post-workout, the author recommends more beta-androstenetriol, whey protein, L-glutamine, L-citrulline, fish oil, and apple to further support immunity and recovery.
Fatty acids carry out many functions that are necessary for maintaining optimal health, and the fatty acid status of a client provides valuable information that relates to both risk and progression of a range of diseases. Determining fatty acid status assists the practitioner in identifying those individuals who would benefit from omega-3 supplementation. The Igennus Opti-O-3 biomarker test is a safe, cost effective and minimally invasive dried blood spot (DBS) method that can be carried out by the client at home. In addition, the Opti-O-3 offers a personalised approach to condition management by focusing on optimising validated biomarkers of disease risk through identification of the client’s unique fatty acid requirements.
In this refresher webinar, Dr Bailey will discuss:
- Fatty acid testing: who, why and when?
- Why choose the Igennus Opti-O-3: a comparison of laboratories
- How to interpret results, including:
- New fatty acid reference ranges
- Overview of fatty acid functions
- Intervention considerations
- Personalised intervention
1) Overexpression of microRNA-146a (miR-146a) in myeloid cells decreases osteoclast differentiation and bone erosion in rheumatoid arthritis (RA) by targeting TRAF6 and IRAK1 proteins critical for osteoclastogenesis.
2) The researcher aims to evaluate the effects of overexpressing miR-146a specifically in myeloid cells in a mouse model of RA induced by mBSA and IL-1β injections using a genetic mouse model that allows tamoxifen-inducible overexpression of miR-146a in myeloid cells.
3) The researcher hypothesizes that overexpressing miR-146a in myeloid cells prior to RA induction will decrease osteocl
This document summarizes a presentation on managing chronic inflammation through modulating fatty acids like omega-3 and arachidonic acid. It discusses how inflammation contributes to diseases like cancer and dementia, and how biomarkers like the omega-3 index, omega-6/omega-3 ratio, and AA/EPA ratio can be used to personalize omega-3 dosing to reduce inflammation. Clinical evidence suggests EPA in particular may help treat inflammation and inhibit cancer progression by competing with arachidonic acid metabolism.
This document reviews the role of reactive oxygen species (ROS) in muscle function and how they may contribute to age-related sarcopenia. ROS are produced in muscles through various pathways including the mitochondrial electron transport chain and NADPH oxidase enzymes. At low levels, ROS play a role in muscle force production and exercise adaptation, but high levels can damage muscles. In aging muscles, ROS levels increase due to reduced antioxidant defenses and may cause cumulative oxidative damage, contributing to sarcopenia through impaired muscle mass, strength, and function.
Exercise metabolism and the molecular regulation of skeletal muscle adaptationviniufrrj
Tthis is a review of the metabolic responses and molecular mechanisms that underpin the adaptatation of skeletal muscle to acute exercise and exercise training.
This document summarizes research on the effects of exercise on gene expression of inflammatory markers in human peripheral blood cells. It reviews 37 studies that examined gene expression in white blood cells like lymphocytes and monocytes after acute and long-term exercise. The studies found that an acute bout of exercise can upregulate expression of some pro-inflammatory genes like IL-1β, IL-8 and CXCL16 in peripheral blood mononuclear cells. However, long-term regular exercise is associated with attenuated inflammatory response and upregulation of anti-inflammatory genes like IL-10 and IL-13. Gene expression changes depend on exercise duration and intensity. The immune system and inflammatory response play a role in diseases like cardiovascular disease and cancer, so understanding
Vladimir Heiskanen - Glycine: The Versatile Anti-inflammatory Nutrient (1st v...Vladimir Heiskanen
This document provides an overview of glycine, an amino acid that can have anti-inflammatory effects. It discusses how glycine may be conditionally essential for humans. Studies show glycine can help prevent metabolic syndrome by reducing inflammation caused by sugar, fat, and alcohol intake. Glycine also appears to protect against stroke and shows benefits for diseases like diabetes, cancer, and liver damage in animal studies. High-dose glycine supplements have helped with conditions like schizophrenia in humans. Dietary sources of glycine include collagen supplements, bone broth, and meat.
Grape Seed Extract : A potential Cancer suppressing agent sudharani028
Natural Polyphenol "Resveratrol" present predominantly in the grape seed plays an very important role in the treatment of devastating disorder Cancer (diseases involving abnormal and uncontrolled growth of cell with the potential to spread to other parts of the body)
This study examines how oxidized phospholipids interact with and activate certain ADAM and ADAMTS proteins in endothelial cells, contributing to inflammation in atherosclerosis. The study finds that oxidized PAPC (Ox-PAPC) activates the enzymatic activities of ADAMTS1 and ADAMTS4, which are involved in regulating the inflammatory chemokine IL-8. Ox-PAPC is shown to covalently bind to ADAMTS1 and ADAMTS4, and promotes cleavage of ADAMTS4 into its mature, active form. This binding and activation of ADAMTS proteins by Ox-PAPC may be one mechanism by which Ox-PAPC induces IL-8 expression
An analysis of metabolic fluxes in contracting human muscleGreg Crowther
This document summarizes research on analyzing metabolic fluxes in human muscle using phosphorus NMR spectroscopy. It discusses:
1. Why studying cellular metabolism in muscle is important, as it can provide insights into whole-body health and lead to medical advances.
2. How phosphorus NMR spectroscopy combined with force measurements can quantify metabolic fluxes non-invasively in vivo by monitoring changes in phosphocreatine and pH levels.
3. Findings that both elevated metabolite levels and a muscle activation factor like calcium are needed to initiate and sustain high glycolysis rates in muscle.
Intermittent fasting and metabolic syndromefathi neana
Dr. Fathi Neana discusses metabolic syndrome and its impact on the musculoskeletal system. Metabolic syndrome is reaching epidemic proportions and is associated with obesity, diabetes, gout, and other conditions that can cause surgical difficulties and complications. Intermittent fasting is presented as a potential strategy for correcting metabolic abnormalities and managing conditions associated with metabolic syndrome like type 2 diabetes.
This study investigated the effects of reducing Fsp27 (fat-specific protein 27) levels through antisense oligonucleotides (ASOs) in mouse models of obesity and insulin resistance. Mice fed a high-fat diet or leptin-deficient ob/ob mice were treated with Fsp27 ASOs. Partial reduction of Fsp27 resulted in decreased visceral fat, improved insulin sensitivity and blood glucose control, and changes in genes related to lipid metabolism. The results suggest that reducing FSP27 activity through ASOs could be a potential therapeutic approach for insulin resistance and obesity in patients.
In this brief review, neuromuscular adaptations to different forms of exercise are reviewed, the positive training effects of eccentric exercise are presented, and the implications for training are considered.
Nutrition is a key factor in the onset and progression of cognitive decline, yet despite a growing pool of research, little evidence exists to support the efficacy of single nutrients in this complex area. The most promising evidence comes from specific dietary patterns and nutrients in the prevention and slowed progression of neurodegenerative disease. During this webinar, Dr Bailey will focus on the synergistic role of key nutrients involved in the mechanisms that drive cognitive decline and support healthy brain aging. Topics include:
- Risk factors for cognitive decline
- Biological mechanisms underpinning cognitive decline
Dietary patterns that offer protection and support against cognitive decline
- The role of specific nutrients in protecting brain health and function
- Nutritional recommendations for healthy brain ageing
1) Timothy Sveeggen conducted mutagenesis experiments on the Mms6 protein, which is involved in iron manipulation in magnetotactic bacteria. He generated two double mutants, S119A/S122A and S119A/E124A, predicted to inhibit the protein's reductase activity.
2) Assays found that the S119A/S122A mutant completely lacked reductase activity, while the S119A/E124A mutant showed mixed results, possibly due to sample precipitation.
3) The study provides insight into Mms6's mechanism of iron reduction and how mutations affect this activity, furthering understanding of biological iron manipulation at the molecular level.
Alina Wilkinson Chem 499 Poster fall 2015(final revision)Alina Wilkinson
This document summarizes a study that compares the effectiveness, mechanism of action, and side effects of nine common NSAID drugs. It finds that NSAIDs work by inhibiting the COX-1 and COX-2 enzymes involved in prostaglandin production, which reduces inflammation, pain, and fever. Certain NSAIDs like ibuprofen, aspirin, and oxaproxin strongly inhibit COX-1, while naproxen sodium, celecoxib, sulindac, etodolac, and diclofenac strongly inhibit COX-2. Acetaminophen is unique in that it does not inhibit either enzyme. All NSAIDs carry side effects like upset stomach, headaches, and rashes
This document discusses potential biomarkers for cancer risk based on estrogen metabolism. It describes how estrogens like estrone and estradiol are metabolized into catechol estrogens that can form quinones and react with DNA. Specific estrogen metabolites, conjugates, and DNA adducts are proposed as possible early biomarkers for breast, prostate, and other cancers. Methods for analyzing estrogens and their metabolites in tissues and blood are also reviewed, with some studies finding higher levels of certain metabolites in cancer patients.
The human papillomavirus (HPV) family consists of over 150 virus types classified into genera based on DNA sequence homology, with the alpha genus containing mucosal HPV types divided into high-risk and low-risk groups depending on their ability to cause cancer, in particular certain high-risk alpha HPV types are established causes of cervical and head/neck cancers.
This document summarizes research on eicosanoids, lipid mediators derived from arachidonic acid that play important roles in inflammation and immunity. It focuses on the roles of prostanoids and leukotrienes in organ transplantation. Prostanoids like prostaglandin E2 and prostacyclin generally have immunosuppressive effects, while thromboxane A2 enhances immune responses. Studies in animals and some human trials suggest these eicosanoids can influence transplant rejection and outcomes. Future research on specific receptors for these lipids may lead to new pharmacological approaches for controlling inflammation and promoting graft acceptance.
1. Arachidonic acid is released from cell membranes and metabolized via either the cyclooxygenase pathway or lipoxygenase pathway to produce prostaglandins, thromboxanes, leukotrienes, and lipoxins.
2. These metabolites are involved in various physiological and pathological processes such as inflammation, hemostasis, smooth muscle contraction, and pain sensation.
3. Nonsteroidal anti-inflammatory drugs function by inhibiting cyclooxygenase, thereby blocking prostaglandin production and reducing inflammation.
This document discusses corticosteroid physiology and principles of corticosteroid therapy. It describes how the adrenal cortex secretes glucocorticoids, mineralocorticoids, and androgens to regulate homeostasis, fluid and electrolyte balance, and secondary sexual characteristics. It notes that prolonged high-dose corticosteroid therapy can suppress the hypothalamic-pituitary-adrenal axis, requiring gradual withdrawal and assessment of axis recovery. Patients with axis suppression may need physiological corticosteroid replacement and stress dosing until recovery is documented. The document also discusses corticosteroid classification, mechanisms of action, effects on metabolism, and principles of physiological corticosteroid replacement therapy.
Neuroendocrine response In trauma and sepsis.pptxBiniam24
The document discusses mitochondrial function and dysfunction. It states that mitochondria generate ATP through oxidative phosphorylation, which can become less efficient and produce reactive oxygen species under stress. This can damage mitochondria and cells. The document also describes how trauma and infection lead to metabolic changes, especially increased breakdown of proteins in muscles, to provide substrates like glutamine to other organs. Hormones and cytokines interact to regulate these metabolic responses.
This document summarizes the pathophysiological links between obesity and type 2 diabetes mellitus (T2DM). It discusses how obesity can cause insulin resistance through mechanisms like glucotoxicity (direct detrimental effects of hyperglycemia on beta cells) and lipotoxicity (toxic effects of elevated fatty acid levels). However, obesity is neither sufficient nor necessary to cause T2DM. The document also explores recent evidence that adipokines (hormones secreted by adipose tissue) may impair glucose tolerance and insulin action by activating inflammatory pathways like NF-κB. While the exact mechanisms are still being elucidated, chronic low-grade inflammation from increased adipokines appears to play an important role in the development of T2DM in susceptible
The document discusses adrenocortical hormone (ACTH) and its role in stimulating the synthesis and secretion of glucocorticoids from the adrenal cortex. It describes the classification, structure, biosynthesis and metabolic effects of glucocorticoids including their effects on carbohydrate, lipid, and protein metabolism. The metabolic effects of glucocorticoids include increased blood glucose levels through effects on gluconeogenesis, glycogenolysis and glucose uptake, as well as increased lipolysis and protein catabolism.
The interaction of Nrf2 and Glyoxalase I in response to lipid loading in Hepa...Farya Mubarik
This document summarizes a study that examined the interaction between Nrf2 and glyoxalase I in response to lipid loading in hepatocytes. The study first optimized the dose and duration of MG132 treatment, a proteasomal inhibitor, to induce accumulation of Nrf2 protein in HepG2 cells. It then examined the effects of oleic acid and palmitic acid on cell viability and found no significant effects. The study aims to determine if inhibition of proteasomal degradation leads to accumulation of Nrf2 and subsequent upregulation of glyoxalase I expression in response to lipid accumulation.
The document discusses two-component systems in bacteria. A two-component system consists of a sensor histidine kinase that autophosphorylates upon sensing a signal and transfers the phosphoryl group to a cognate response regulator. The response regulator then undergoes a conformational change and activates or represses target genes. The system allows bacteria to sense and adapt to various stressors like oxidative stress and nutrient starvation.
pharmacology of Adrenocorticosteroids final.pptNorhanKhaled15
The document discusses adrenocortical hormones and corticosteroids. It covers their production, secretion controlled by ACTH, classification, pharmacokinetics, mechanisms of action, physiologic effects, synthetic corticosteroids, use for diagnostic purposes, treatment of adrenal disorders like Cushing's syndrome and congenital adrenal hyperplasia, and toxicity. The major points are the production and regulation of corticosteroids, their metabolic, anti-inflammatory and other effects, uses in diagnosis and treatment of adrenal disorders, and risks of long-term use.
Abstract
Mitogen-Activated Protein Kinase (MAPK) pathway is a signal transduction pathway that functions in a wide range of physiological and pathophysiological cellular events including cell proliferation, differentiation, apoptosis, migration, inflammation, metabolic disorders and diseases. In skeletal muscle, it plays an essential role in muscle fiber specialization, muscle mass maintenance, damage induced muscle regeneration and muscle diseases. This review provides an overview of MAPK pathway and its pathophysiological role in skeletal muscle diseases with a primary focus on muscular dystrophy and atrophy.
Insulin resistance occurs when cells become less responsive to insulin. It can be caused by genetic or diet-induced factors, with obesity being the most common cause. Insulin resistance is associated with inflammation, oxidative stress, and lipid accumulation in tissues like muscle and fat cells. Disrupted gut microbiota may also contribute by impacting energy harvest and metabolite production. Regulators of insulin sensitivity include PPARγ, AMPK, mTOR, and sirtuins, which control pathways involved in glucose and fatty acid metabolism. Gene expression analysis using PCR arrays can help study mechanisms of insulin resistance.
1) The study examined the effects of diethyl hexyl phthalate (DEHP) exposure on insulin signaling molecules and glucose metabolism in the triceps muscle of rats.
2) Rats treated with DEHP showed increased oxidative stress, reduced insulin receptor and glucose transporter 4 (GLUT4) levels, and decreased glucose uptake and oxidation in the triceps muscle.
3) Co-treatment with antioxidants vitamins C and E prevented the adverse effects of DEHP by reducing oxidative stress, and protecting insulin signaling molecule levels and glucose metabolism in the triceps muscle.
Artemisinin relieves osteoarthritis by activating mitochondrial autophagy through reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling in cartilage. The study found that artemisinin treatment downregulated cartilage degradation proteins and inflammatory factors in IL-1β-stimulated chondrocytes. Gene sequencing revealed that artemisinin treatment significantly downregulated TNFSF11 expression, which encodes RANKL, a factor involved in osteoclast formation. The study also showed that artemisinin activated autophagy and relieved cartilage damage by inhibiting the PI3K/AKT/mTOR signaling pathway in IL-1β-induced chondrocytes.
Derived from the bacterium Proteus vulgaris , chondroitin ABC lyase is an enzyme that can be used in treating proteoglycans that
affect neural activity (communication, plasticity). Chondroitinase can be used for vision abnormalities and spinal injuries. The
biological activity of chondroitinase is due to its ability to act on chondroitin sulfate proteoglycans (CSPGs) which are required for
normal functioning. Th is study aim s to examine various types and routes of administration of Chondr oitina se e n zymes. There is an
increasing application of chondro itin sulfate proteoglycans in spinal cord injury, vit reous attachment, and the management of
various carcinogenic conditions. Research must be done to create an effective chondroitinase delivery mech anism so that the
pharmacological activity seen in vitro and in preclinical research may be applied in the clinic. More studies are required to widen
the application of chondroitinase in therapeutics. In this review, chondroitinase ABC, B, and C are all di scuss ed. T he routes of
administration like caudal or ros tral, intracerebroventricular, hydrogels, and intrath ecal have been detailed. The current review
article highlights the different medical uses for chondroitinase, drug delivery methods for the enzym e, and chondroitinase
dispersion across bacteria. In conclusion, this study can reduce the chance of edema by the intracerebroventric ular route.
However, it is not effective for people due to the gyrencephalic anatomy of brain
Key-words: Chondroitinase, Chondroitin, Chondroitin Sulfate Proteoglycans, Spinal Injuries, Ocular Abnormalities, Proteoglycans
This document discusses steroidal anti-inflammatory drugs, specifically glucocorticoid hormones. It describes the effects of glucocorticoids on various body systems and metabolic processes, including carbohydrate, protein and lipid metabolism, as well as water and electrolyte balance. It also discusses the anti-inflammatory, anti-allergic, and immunosuppressive mechanisms and effects of glucocorticoids. Finally, it outlines the indications, tactics, complications, contraindications of glucocorticoid therapy.
The role of NSAIDs in periodontal disease progressionHope Inegbenosun
This document discusses the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in periodontal disease progression. It outlines that periodontal disease results from the host inflammatory response to bacterial pathogens and involves the production of arachidonic acid metabolites like prostaglandin E2 (PGE2) that promote tissue destruction. NSAIDs inhibit the enzyme cyclooxygenase and thereby reduce PGE2 levels to decrease inflammation and bone resorption. Both animal and human studies show that systemic or local NSAID administration can suppress periodontal disease progression by limiting inflammation and PGE2 production.
This document provides an overview of corticosteroid therapy. It discusses the types and doses of corticosteroids used, their mechanisms of action both genomic and non-genomic, indications for use, side effects, and guidelines for administration timing and withdrawal. Corticosteroids are powerful anti-inflammatory drugs that are widely used but also have numerous side effects, so their risks and benefits must be carefully considered.
Similar to Corticosteroid induced disorders – an overview (20)
Patient compliance: Challenges in management of cardiac diseases in Kuala Lum...pharmaindexing
Background
The objective of this study was to investigate the degree of compliance among cardiac patients who attend the health facilities in Kuala Lumpur and Perak, Malaysia. The reasons for non-compliance and recommendations from healthcare professionals were also evaluated.
Method
A cross-sectional study of 400 patients and 100 healthcare professionals was carried out. This study utilizes variables on external factors and internal factors as the measurement tools. The questionnaire which consists of Morisky self-reported medication adherence questions was administered to patients and causes for non-compliance sought. Questionnaire for healthcare professionals was used to determine strategies that can improve compliance rate.
Results
The study revealed a 15.8% of high adherence rate, 54.3% of moderate adherence rate and 30% of poor adherence to cardiovascular disease medications. The chi-square tests showed the strong association between dependent and independent variables. The model chosen for testing the patient compliance through external and internal factors gives an R2 value of 85.0% with an adjusted R2 of 84.7%. The F value (317.187) was also significant (p=0.000) which means that the variables have better fit in the multivariate model. The major reasons determined for non-adherence were attitudes and beliefs, lifestyle, side effects and cost of medications. The study recommends that pharmacists and dispensing technicians should be adequately qualified to provide proper counselling to cardiac patients on their medicines and disease conditions.
Conclusion
The result of this study is of value to health care providers. Compliance to cardiovascular medications will avoid treatment failures encountered in therapy.
Overview on Recurrence Pregnancy Loss etiology and risk factorspharmaindexing
Recurrent pregnancy loss (RPL) can be defined as more than two to three consecutive miscarriages before 20 weeks’ gestation; it affects approximately 1% to 2% of women. RPL is a multifactorial disease. It is very important to study the etiology and risk factors of RPL to find the best diagnostic tests and suitable therapeutic intervention. This article will discuss the current understanding etiologies and risk factors of RPL.
Novel treatments for asthma: Corticosteroids and other anti-inflammatory agents.pharmaindexing
Asthma management is a challenge due to the prevalence of disease in the world. Based on the immunological and inflammatory mechanisms of asthma, corticosteroids and anti-inflammatory participate greatly in the treatment plan. Due to different reasons, there is still an unmet need to develop new agents in this field. A lot of compounds with anti-inflammatory effect are investigated in both pre-clinical and clinical studies.
A review on liver disorders and screening models of hepatoprotective agentspharmaindexing
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of bio chemicals necessary for digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function long term, although liver dialysis can be used short term.
Carbamazepine induced Steven Johnson syndrome: A case reportpharmaindexing
Drugs are the most common cause that induces Steven Johnson syndrome (SJS) and includes antiepileptic drugs, antiretroviral drugs, anti-tuberculosis drugs, Sulphonamides, fluoroquinolones, penicillins, non-Steroidal anti-inflammatory drugs, Multivitamins. The genetic markers are also the cause for carbamazepine induced Steven Johnson Syndrome. In our study, the antiepileptic drug (Carbamazepine) is the cause for Steven Johnson Syndrome. A female patient aged 25 years came to the hospital with the complaints of bubbling over the skin and all over the body with papillary vesicles associated with pain and irritation, fever, myalgia, and nausea. The patient is known case of Phenytoin induced Steven Johnson Syndrome. In this case the patient developed the Steven Johnson Syndrome approximately after one month after starting the carbamazepine.By the withdrawal of the drug, the condition of the patient was improved.
Monoherbal formulation development for laxative activitypharmaindexing
The Ayurvedic Pharmacopoeia specifically approves flaxseed as a poultice for boils externally and demulcent or laxative internally. In this study monoherbal formulation development for laxative activity of flaxseed was undertaken. The plantLinumusitatissimumhasshowed higher percentage of total ash as well as alcohol soluble extractive values. The aqueous extract of Linumusitatissimumwas prepared by using pilot scale extraction plant and spray drying unit. The qualitative phytochemical studies reveal the presence of amino acids, carbohydrates, vitamins and proteins. From the available literatures it was found that Linumusitatissimum contains more number of amino acids. The formulated tablets showed acceptable pharmacopoeial limits and complies with specifications for thickness, hardness, friability and weight variation. The formulation has showed better laxative activity indicating additive property of the combined phytoconstituents of the plant.
Monoherbal formulation development for laxative activitypharmaindexing
The Ayurvedic Pharmacopoeia specifically approves flaxseed as a poultice for boils externally and demulcent or laxative internally. In this study monoherbal formulation development for laxative activity of flaxseed was undertaken. The plantLinumusitatissimumhasshowed higher percentage of total ash as well as alcohol soluble extractive values. The aqueous extract of Linumusitatissimumwas prepared by using pilot scale extraction plant and spray drying unit. The qualitative phytochemical studies reveal the presence of amino acids, carbohydrates, vitamins and proteins. From the available literatures it was found that Linumusitatissimum contains more number of amino acids. The formulated tablets showed acceptable pharmacopoeial limits and complies with specifications for thickness, hardness, friability and weight variation. The formulation has showed better laxative activity indicating additive property of the combined phytoconstituents of the plant.
Pneumonia and respiratory failure from swine origin influenza H1n1pharmaindexing
Swine influenza (swine flu) became alarming health concern when World Health Organization declared as “public health emergency of international concern” on April 25, 2009. After documentation of human-to-human transmission of the virus in at least three countries of two WHO regions, the WHO raised the pandemic level to 6.1 During the 1918, flu pandemic infected one-third of the world's population (an estimated 500 million people) and caused approximately 50 million deaths.2 In 1976, an outbreak of swine influenza occurred in New Jersey, USA, which involved more than 200 cases, some of them severe, resulting in one death.3 In 1988, another fatality was reported as a complication of swine influenza.
A descriptive study on newborn care among postnatal mothers in selected mater...pharmaindexing
The newborn health challenge faced by India is more formidable than that experienced by any other country in the world. The newborn health is inevitably affected by the traditional care practices of the mothers causing high infant morbidity and mortality.The aim of the study were determine the knowledge, attitude and practice of postnatal mothers regarding new born care and find out the association between knowledge, attitude and practice of postnatal mothers regarding new born care and to determine the association between these as well as with the selected demographic variables. A descriptive study was conducted to assess the knowledge, attitude and practice of postnatal mothers regarding new born care in selected maternity centres in Madurai. Survey approach was employed to select sample and it consisted of 100 postnatal mothers. Data was collected using structured interview schedule. Findings of the study showed that 65% of postnatal mothers had moderate knowledge; 61% had favourable attitude and 57% of them had high practice of new born care. There was a significant association between knowledge and attitude (r=+0.567), knowledge and practice (r=+0.388), attitude and practice (r=+0.321) .There was a significant association between knowledge and education, monthly family income and obstetrical score at p<0.05. Findings of the study indicated the need to conduct frequent assessment of knowledge, attitude and practice of postnatal mothers regarding new born care. Awareness and attitude of the mothers towards new born care still has lots of lacunae especially in those who belong to the lower socio economic statusand poorly educated postnatal mothers. So it is imperative to provide comprehensive training in the field of new born care for mothers during pregnancy
Late 19th century was evident of intelligent biomaterial; which has changed researcher’s perspective towards science and technology. This intelligent biomaterial are envisioned to have huge impact on Healthcare from sequential signalling of biomedical molecule, mimicking natural gene, an effective drug carrier, to high resolution diagnostic tool.From drug discovery aspect many of NCE fail to reach therapeutic potential due to PK/ PD profile. Nanotechnology has changed the face of drug discovery form chemical evaluation to structure of proteins in signalling pathways and development of chemical antibody. Nanotechnology from lab to market approval is long process due to regulatory evaluation. Though it seems to be bright future market it has to go through a long process from being innovation to complete market product. This makes whole process expensive making investor reluctant to invest in big projects.Western world is aware of dramatic potential of nano-projects; which has its limitation in financial investments; with major challenge of transforming nano science to commercial pharmaceutical product.
The Flaws in health practice in post-operative management of a patient in ter...pharmaindexing
This case study summarizes the treatment of a 4-year old child with congenital urinary tract obstruction who presented with constipation, fever, and cough. Laboratory tests found low electrolyte levels, high blood acids, and kidney damage. The child's treatment included surgery, dialysis to correct electrolyte imbalances, and antibiotics for chest infection. However, the case study notes discrepancies in the post-operative treatment, including questionable antibiotic selection and prescribing of calcium channel blockers not recommended for children. The study concludes there is a need for clinical pharmacists on the healthcare team to improve rational medication use.
Corticosteroid induced disorders – An overviewpharmaindexing
Glucocorticoids are important in the treatment of many inflammatory, allergic, immunologic, and malignant disorders, and the toxicity of glucocorticoids is one of the commonest causes of iatrogenic illness associated with chronic inflammatory disease.Glucocorticoid-induced muscle atrophy is characterized by fast-twitch or type II muscle fiber atrophy. Corticosteroid (CS) therapy is widely used in the treatment of rheumatic diseases.Osteoporosis remains one of its major complications.Steroid induced glaucoma is a form of open angle glaucoma occurring as an adverse effect of corticosteroid therapy. Glucocorticoids induce hepatic and extrahepatic insulin resistance.Glucocorticoid treatment impairs both glucose transport in fat and muscle cells. Corticosteroid-induced psychosis represents a spectrum of psychological changes that can occur at any time during treatment. Cushing’s syndrome describes the signs and symptoms associated with prolonged exposure to inappropriately high levels of the hormone cortisol. Physicians must be aware of these adverse effects and be equipped to manage them.
Anti-inflammatory activity of pupalia lappacea L. Jusspharmaindexing
Pupalia lappacea (L) Juss is an erect shrub used in folklore medicine to treat bone fractures and in inflammatory conditions. Methanolic extract of aerial parts shown is claimed in traditional medicine that the leaves of the plant are used in the treatment of inflammation. In the present study, the methanolic extract of Pupalia lappacea was screened for its anti-inflammatory activity using carageenan induced rat paw edema egg white induced paw oedema models. The methanolic extract at the dose of 200 mg/kg p.o exhibited significant anti-inflammatory activity in carrageenan induced paw edema model (p<0.01). In egg white induced model, methanolic extract at the dose of 200 mg/kg inhibited paw oedema significantly (p<0.01) indicating that both test samples inhibit the increase in number of fibroblasts and synthesis of collagen and mucopolysaccharides during prostaglandin formation during the inflammation. These experimental results have established a pharmacological evidence for the folklore claim of the drug to be used as an anti inflammatory agent. HPTLC analysis of the extract shows the presence of gallic acid 1.24mg/ml, ferulic acid 2.00mg/ml, chlorogenic acid 46.25mg/ml and rutin 7.02mg/ml of the extract which were responsible for the claimed anti-inflammatory action in the animal models studied.
Lucinactant: A new solution in treating neonatal respiratory distress syndrom...pharmaindexing
This document summarizes research on Lucinactant, a novel synthetic surfactant approved by the FDA in 2012 for treatment of neonatal respiratory distress syndrome (RDS). It contains a peptide called sinapultide that mimics the function of human surfactant protein B. Studies found Lucinactant was as effective as or more effective than previous animal-derived surfactants in reducing mortality from RDS, but its pharmacokinetics are not fully understood. The document reviews clinical trials and mechanisms of Lucinactant and discusses its efficacy, safety profile, and potential cost benefits compared to other surfactants.
Bioactivity screening of Soil bacteria against human pathogenspharmaindexing
This study aimed to isolate soil bacteria with potential bioactive properties against human pathogens. 36 bacterial strains were isolated from 3 soil samples and screened against common pathogens. 14 isolates showed antibacterial activity, including against Staphylococcus aureus, Streptococcus faecalis, E. coli, Klebsiella aerogenes, Proteus vulgaris, Pseudomonas aureginosa and Salmonella typhi. The 3 most active bacterial isolates were selected for further production and isolation of their bioactive metabolites. Testing found the metabolites had prominent antibacterial effects against the clinical pathogens studied, indicating their potential as a source of new antimicrobials given the rise in drug resistance.
A study on sigmoid Volvulus presentation and managementpharmaindexing
A study on sigmoid volvulus presentation and management was a 2yr retrospective study done at RMMCH.The diagnosis of sigmoid volvulus was made from a history of large bowel obstruction (constipation, abdominal distension, and abdominal pain), which were often recurrent and plain abdominal radiographs.The morbidity associated isSuperficial wound infection occurred in four patients. All the infected wounds eventually healed with conservative measures. Clinical anastomotic dehiscence was noted in 1 patient for which during relaparotomy proximal colostomy and mucous fistula was done. The mortality associated is shown is there were 9 deaths of which 7 were due to sepsis and 2 were due to comorbid illness. Two out of eight patients for whom a colopexy was done had a recurrent attack of sigmoid volvulus. The duration of hospital stay ranged between 10 and 21 days. Use of sigmoidoscopic detorsion for viable colon should be encouraged. Sigmoidopexy, which is associated with a recurrence rate of 20% in our series of patients, should be used selectively.Hartmann’s procedure is a safe option in sigmoid volvulus with gangrenous bowel. Primary anastomosis in emergency situation can be carried out with morbidity and mortality in patients with viable colon
Evaluation of Preliminary phytochemical on various some medicinal plantspharmaindexing
The present study was carried out to evaluate the physical status and percentage yield of methanolic extract and its fractions of whole plant of Leucas cephalotes, leaves of Hiptage benghalensis and leaves of Kydia calycina were recorded for future references and Preliminary phytochemical screening of MLC, MHB and MKC revealed the presence of carbohydrates, glycosides, saponins, flavonoids, steroidal and phenolic compounds. MLC revealed the presence of all the above mentioned phytoconstituents except saponins and also MKC steroidal compounds. The fractions of MLC, MHB and MKC revealed the presence of glycosides, phenolic compounds, steroids and flavonoids.
Comparision of in vitro antibacterial activity of cefoperazone and levofloxac...pharmaindexing
This study compared the in vitro antibacterial activity of cefoperazone and levofloxacin against various clinical isolates. 120 bacterial isolates from patient samples were tested for susceptibility to cefoperazone and levofloxacin using disc diffusion. Results showed levofloxacin had lower resistance than cefoperazone for E. coli and P. aeruginosa, while cefoperazone was more effective against S. aureus. However, resistance to both antibiotics was gradually increasing, highlighting the need for regular surveillance of antibiotic susceptibility.
Concept of srotas from ayurvedic perspective with special reference to neurologypharmaindexing
Ayurveda is a life science. The researchers of ayurveda could rule out the presence of srotas (channels) spreading throughout the human body. These srotas (channels) are governed by vayu which is using all the srotas (channels) of the body to carry out the functional and physiological activities of the human body without which the human society will not exist. Several synonymous words have been described by the ayurvedicacharyas for srotas. Some are micro and some are macro in structures and they adopt the same colour of the particular dhatus of the body to which it belongs. The aim of the study is to justify that srotas are nothing but innurmerable channels or pathways of the nervous system governed by electric current without which no functional and physiological activities of the human body will develope.
Health promotion survey in overweight and obese students of universities in n...pharmaindexing
Introduction
Overweight and obesity is one of the major health problems in the UK and worldwide. Approximately two-thirds of the population in the UK is either overweight or obese. Overweight and obesity is an important issue that causes distress to most women. Health promotion is the best method to educate overweight and obese women. It is defined as the process enabling people to increase control over and to improve their health by Ottawa Charter for Health Promotion. It is aimed to enhance the well-being of the individuals and their positive attitudes towards prevention of various diseases. In order to make any improvement to the health promotion for overweight and obesity, the risk factors and the opinions from the public should first be identified and addressed.
Methods
Cross-sectional survey design was selected with a questionnaire that consisted of 20 open and close ended questions. A sample size of 196 was determined. The data thus gathered was analyzed using SPSS V20 (Statistical Package for Social Science version 20). Descriptive statistics (fx) and (SD) were used and Chi-square X2 test for association was employed.
Results
Out of the total 196 responses, only (40%) of the students had normal weight (SD 1.1), (25%) students had a good understanding of health promotion (SD 1.6), half (50%) appeared concerned about their weight (SD 0.5), (60%) had an obese family member (0.5). The BMI of students was associated with the presence of an obese member in their family and their weight as a concern for them. (P-value <0.05).
Conclusion
The health promotion service is beneficial as it was found to have raised concerns in the mind of the students regarding over weight and obesity. However it was observed that the understanding of health promotion service was different among students and this is the root of the problem.
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!
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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
- 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
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.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
1. ~ 102 ~
* Corresponding author: Koppula Shilpa.
E-mail address: koppulashilpa108@gmail.com
IJAMSCR | Volume 2 | Issue 2 | April - June - 2014
www.ijamscr.com
Review article
Corticosteroid induced Disorders – An overview
Koppula Shilpa*, Gangisetty Sneha, Nallani Venkata Ramarao, Rama Rao Nadendla.
Department of Pharmacy Practice, Chalapathi Institute of Pharmaceutical Sciences, LAM, Guntur,
Andhra Pradesh, India.
ABSTRACT
Glucocorticoids are important in the treatment of many inflammatory, allergic, immunologic, and
malignant disorders, and the toxicity of glucocorticoids is one of the commonest causes of iatrogenic
illness associated with chronic inflammatory disease. Glucocorticoid-induced muscle atrophy is
characterized by fast-twitch or type II muscle fiber atrophy. Corticosteroid (CS) therapy is widely
used in the treatment of rheumatic diseases. Osteoporosis remains one of its major complications.
Steroid induced glaucoma is a form of open angle glaucoma occurring as an adverse effect of
corticosteroid therapy. Glucocorticoids induce hepatic and extrahepatic insulin resistance.
Glucocorticoid treatment impairs both glucose transport in fat and muscle cells. Corticosteroid-
induced psychosis represents a spectrum of psychological changes that can occur at any time during
treatment. Cushing’s syndrome describes the signs and symptoms associated with prolonged exposure
to inappropriately high levels of the hormone cortisol. Physicians must be aware of these adverse
effects and be equipped to manage them.
Key words: Corticosteroids, Myopathy, Osteoporosis, Glaucoma, Diabetes Mellitus, Psychosis,
Cushing’s Syndrome.
INTRODUCTION
Corticosteroids are a class of chemicals that
includes steroid hormones naturally produced in
the adrenal cortex of vertebrates and analogues of
these hormones that are synthesized in laboratories.
The corticoids have widespread actions. They
maintain fluid-electrolyte, cardiovascular and
energy substrate homeostasis and functional status
of skeletal muscles and nervous system.
Glucocorticoids are important in the treatment of
many inflammatory, allergic, immunologic, and
malignant disorders, and the toxicity of
glucocorticoids is one of the commonest causes of
iatrogenic illness associated with chronic
inflammatory disease. Numerous toxicities, or
adverse effects, have been attributed to
glucocorticoids.1
MECHANISM OF ACTION OF
CORTICOSTEROIDS
The glucocorticoid (G) penetrates the cell
membrane and binds to the glucocorticoid receptor
(GR) protein that normally resides in the cytoplasm
in association with 3 other proteins, viz. Heat shock
protein 90 (HSP90), HSP70 and immunophilin
(IP). The GR has a steroid binding domain near the
caboxy terminus and a mid region DNA binding
domain having two “Zinc fingers”, each made up
of a loop of amino acids with chelated zinc ion.
Binding of the steroid to GR dissociates the
complexes proteins (HSP90, etc) removing their
inhibitory influence on it. A dimerization region
that overlaps the steroid binding domain is
exposed, promoting dimerisation of the occupied
receptor. The steroid bound receptor
International Journal of Allied Medical Sciences
and Clinical Research (IJAMSCR)
2. Koppula Shilpa et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-2(2) 2014 [xxx-xxx]
www.ijamscr.com
~ 103 ~
diamertranslocates to the nucleus and interacts with
specific DNA sequences called ‘glucocorticoid
responsive elements’ (GRES) within the regulatory
region of appropriate genes. The expression of
these genes is consequently altered resulting in
promotion (or suppression) of their transcription.
The specific mRNA thus produced is directed to
the ribosome where the message is translated into a
specific pattern of protein synthesis, which inturn
modifies cell function.2
CORTICOSTEROIDS INDUCED MYO-
PATHY3
Glucocorticoid-induced muscle atrophy is
characterized by fast-twitch or type II muscle fiber
atrophy illustrated by decreased fiber cross-
sectional area and reduced myofibrillar protein
content.
PATHOPHYSIOLOGY
Mechanisms of glucocorticoid-induced muscle
atrophy
In skeletal muscle, glucocorticoids decrease the
rate of protein synthesis and increase the rate of
protein breakdown 4,5,6
contributing to atrophy. The
severity and the mechanism for the catabolic effect
of glucocorticoids may differ with age. For
example, glucocorticoids cause more severe
atrophy in older rats compared with younger rats.
Furthermore, glucocorticoid-induced muscle
atrophy results mainly from increased protein
breakdown in adult rats but mostly from depressed
protein synthesis in the aged animals7
.
Anti-anabolic action of glucocorticoids
The inhibitory effect on protein synthesis results
from different mechanisms. First, glucocorticoids
inhibit the transport of amino acids into the
muscle8
, which could limit the protein synthesis.
Secondly, glucocorticoids inhibit the stimulatory
action of insulin, insulin-like growth factor-I (IGF-
I), and amino acids (in particular leucine), on the
phosphorylation of eIF4E-binding protein 1 (4E-
BP1) and the ribosomal protein S6 kinase 1
(S6K1), two factors that play a key role in the
protein synthesis machinery by controlling the
initiation step of mRNA translation9,10
. Finally,
there is also evidence that glucocorticoids cause
muscle atrophy by inhibiting myogenesis through
the down regulation of myogenin, a transcription
factor mandatory for differentiation of satellite cells
into muscle fibers.
Catabolic action of glucocorticoids
The stimulatory effect of glucocorticoids on muscle
proteolysis results from the activation of the major
cellular proteolytic systems, namely the ubiquitin–
proteasome system (UPS), the lysosomal system
(cathepsins), and the calcium-dependent system
(calpains). The protein degradation caused by
glucocorticoids affects mainly the myofibrillar
proteins as illustrated by the increased excretion of
3-methyl histidine. To activate the protein
degradation, glucocorticoids stimulate the
expression of several components of the UPS either
involved in the conjugation to ubiquitin of the
protein to be degraded (ubiquitin; 14 kDa (E2), a
conjugating enzyme; atrogin-1 and MuRF-1, two
muscle-specific (E3) ubiquitin ligases; or directly
responsible for the protein degradation by the
proteasome (several subunits of the 20S
proteasome). This gene transcription activation is
associated with an increased rate of protein
ubiquitination and increased proteolytic activities
of the proteasome itself.
Using blockers of the different proteolytic
pathways, evidence was found that glucocorticoids
stimulate not only the UPS-dependent proteolysis
but also the calcium-dependent and lysosomal
protein breakdown. The role of lysosomal system
in the atrophic effect of glucocorticoids is also
suggested by the increase in cathepsin L muscle
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expression in glucocorticoid-treated
animals11
.Because the proteasome does not degrade
intact myofibrils, it is thought that actin and myosin
need to be dissociated (probably by calpains) from
the myofibrils before they can be degraded by the
UPS. Finally, some in vivo data also suggest that
caspase-3 can be implicated in the myofibrillar
proteins breakdown induced by glucocorticoids.
Indeed, in glucocorticoid-dependent muscle
wasting models, such as diabetes mellitus and
chronic renal failure, caspase-3 activity in muscle is
increased and inhibition of caspase-3 by Ac-
DEVD-CHO, a peptide inhibitor, suppresses the
accelerated muscle proteolysis. However, the role
of glucocorticoids in the induction of caspase-3
activity in these models has not yet been explored.
Prevention of glucocorticoid-induced
muscle atrophy
Growth factors
Stimulation of IGF-I and inhibition of MSTN
appear promising therapeutic tools to attenuate
glucocorticoid-induced muscle atrophy13
. Indeed,
muscle IGF-I overexpression12
or myostatin
deletion14
prevents glucocorticoid-induced muscle
atrophy. Therefore, IGF-I stimulation or MSTN
blockade might be beneficial for a variety of
myopathies, such as the ones caused by high doses
of glucocorticoids. Further experiments are needed
to test this possibility.
Branched chain amino acids (BCAAs)
Provision of the BCAAs mimics the effect of a
complete mixture of amino acids in stimulating
protein synthesis in skeletal muscle15
. Of the
BCAAs, leucine appears to be the most important
in stimulating protein synthesis. Therefore, it seems
logical to propose to override the catabolic effects
of glucocorticoids toward skeletal muscle by
administration of BCAAs or leucine alone.
However, the fact that glucocorticoids make the
muscle protein synthesis resistant to exogenous
BCAAs and leucine does not support this
hypothesis.
Glutamine
Glutamine is a conditional essential amino acid in
catabolic states. Glutamine and alanyl-glutamine
have been reported to prevent glucocorticoid-
induced muscle atrophy. However, attenuation of
this muscle atrophy by glutamine infusion is not
associated with changes in circulating IGF-I levels.
In contrast, administration of glutamine prevents
glucocorticoid-induced Mstn expression, which
suggests that glutamine may inhibit the atrophic
effect of glucocorticoids on muscle strength
through inhibiting Mstn.
Taurine
Since ablation of taurine transporter gene results in
susceptibility of exercise-induced weakness in vivo,
it has been suggested that this transporter is
essential for skeletal muscle function. The role of
taurine in the prevention of glucocorticoid-induced
atrophy is suggested by two observations. First,
taurine attenuates muscle cell atrophy caused by
glucocorticoids in vitro. Second, induction of
taurine transporter prevents glucocorticoid-induced
muscle cell atrophy. Although attractive, the
possibility for taurine to attenuate glucocorticoid
effects on skeletal muscle warrants further
investigations.
Creatine
Dietary supplementation with creatine
monohydrate has been shown to attenuate the
muscle weight loss and the atrophy of
gastrocnemius type IIb fibers caused by
glucocorticoids. Furthermore, this protective effect
was associated with an attenuation of the
impairment of daily spontaneous running of
animals receiving glucocorticoids 16
. Although
further work is required to determine the specific
mechanisms underlying the effects of creatine on
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muscle, evidence collected in vitro suggests that
creatine may act on muscle cells by increasing
IGF-I expression.
Clenbuterol
Clenbuterol, a β2-adrenergic receptor agonist used
to increase muscle mass in cattle, has been tested to
prevent glucocorticoid-induced muscle atrophy.
Experiments have shown that clenbuterol is able to
blunt at least partially the skeletal muscle atrophy
caused by dexamethasone. However, on
diaphragm, attenuation of muscle atrophy was not
associated with a protective effect on muscle
dysfunction. Evidence collected in vivo suggest that
clenbuterol may exert its anti-catabolic effect on
muscle by increasing IGF-I expression ,while down
regulating Mstn expression.
Androgens
Administration of androgens, such as testosterone
or nandrolone, a minimally aromatizable analog,
prevents decreased muscle mass and strength
caused by glucocorticoids in animals and humans.
Although the molecular mechanisms by which
testosterone attenuates the effects of
glucocorticoids are not fully elucidated,
testosterone, like many other anabolic stimuli,
appears to stimulate muscle IGF-I expression.
CORTICOSTEROIDINDUCED
OSTEOPOROSIS
Corticosteroid (CS) therapy is widely used in the
treatment of rheumatic diseases. Osteoporosis
remains one of its major complications.
MECHANISM
The mechanism of CIOP is uncertain but appears
different from that of post-menopausal
osteoporosis. A major difference is that bone
formation appears to be suppressed by CS 17
. This
may be difficult to confirm in direct studies
because although osteocalcin, a marker of bone
formation, has been shown to be suppressed by CS
therapy18, 19
, this may be due to a direct effect of CS
on the osteocalcin gene promoter to antagonize the
action of 1,25(OH)2D3 to induce the gene 20
. The
effects of CS on bone resorption are more difficult
to assess because although some studies suggest
that resorption is increased 18,19
, others 21,22
have
shown no effect.
The result of the greater depression of bone
formation compared with bone resorption
(remodeling imbalance) leads to differences in
bone microanatomy and histology. In post-
menopausal osteoporosis, the reduction in
trabecular bone volume due to an increase in bone
resorption appears to be due to trabecular
discontinuity, whereas the reduction in trabecular
bone volume due to decreased bone formation in
CIOP is a result of trabecular thinning 23
. This has
implications for both the diagnosis and treatment of
CIOP.
Other factors involved in the development of CIOP
include alterations in the calcium regulating
hormones and sex steroids. Intestinal calcium
absorption is reduced as a result of CS use17
which
also leads to a reduced renal tubular calcium
reabsorption. Although these changes were initially
thought to be due to secondary
hyperparathyroidism, recent studies measuring the
intact parathyroid hormone (PTH 1–84) have
shown these values to be normal19
. There is also an
alteration in hypothalamic gonadotrophin releasing
hormone secretion17
with subsequent reduction in
serum testosterone24
and oestradiol levels 25
.
Finally, CS therapy may influence cellular
responses within the bone micro environment by
modulating cytokines that act locally to regulate
remodeling and these factors include interleukin1,
tumour necrosis factor and insulin like growth
factor.26
TREATMENT
Many agents used in postmenopausal osteoporosis
such as activated vitamin D products, hormone
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replacement therapy, fluoride, calcitonin and the
bisphosphonates have been shown to maintain or
improve BMD in CIOP. Primary prevention is
treatment started at the time of initiation (up to
3 months) of CS therapy. Secondary prevention is
treatment started >1 yr after the initiation of CS
therapy or following an osteoporotic fracture and
implies established bone loss. All patients should
be assessed for hypogonadism and if present, HRT
should be offered to women and testosterone to
men27,28,29
CORTICOSTEROID-INDUCED GLAUCOMA
A rise in intraocular pressure (IOP) can occur as an
adverse effect of corticosteroid therapy. If the
ocular hypertensive effect is of sufficient
magnitude, for an adequate duration, damage to the
optic nerve (steroid-induced glaucoma) may ensue.
Corticosteroids are believed to decrease outflow by
inhibiting degradation of extracellular matrix
material in the trabecular meshwork (TM), leading
to aggregation of an excessive amount of the
material within the outflow channels and a
subsequent increase in outflow resistance.30,31
PATHOPHYSIOLOGY39
Corticosteroids cause elevation of IOP by
decreasing the facility of aqueous eye flow
.Steroids specific receptors on the trabecular
meshwork cells may play a role in the development
of steroid induced glaucoma. Recent research has
elucidated the possible role of genetic influences in
the pathophysiology.
The main mechanism of action of steroids i.e;
responsible for glaucoma is their membrane
stabilizing action. Hyaluronidase sensitive
glycosaminoglycans (mucopolysacchrides) are
normally present in the aqueous out flow system.
These glycosaminoglycans in the polymerised form
may undergo hydration producing a ‘biologic
oedema’. Hence, these are constantly degraded by
the hyaluronidase with in the lysosomes of the
goniocytes
The steroids stabilize the lysosomal membrane of
the goniocytes and thus lead to an accumulation of
polymerised glycosaminoglycans in the trabecular
meshwork, producing an increased outflow
resistance. Glucocorticoid administration increases
expression of collagen, elastin, and fibronectin with
in the trabecular meshwork and induces expression
of sialoglycoprotein .
Another mechanism proposed is that steroids
inhibit phagocytosis by the endothelial cells lyning
the trabecular meshwork. This leads to an
accumulation of debris with in the meshwork.
There is also extra cellular deposition of finger
print like material.
Steroid use decreases expression of extra cellular
proteinases including fibrinolytic enzymes and
stromolysin.
A decrease in the synthesis of prostaglandins by
corticosteroids, that regulate aqueous facility has
also been proposed as one of the mechanisms
leading to increasing IOP.
Management of corticosteroid-induced
glaucoma
Monitoring of IOP32
Cessation of corticosteroid treatment34
Alternative corticosteroid formulations33,36,37
Topical treatments can be changed to
preparations such as fluoromethalone 0.1% or
rimexolone 1%, which are claimed to have less
effect on IOP,or in certain situations to
nonsteroidal anti-inflammatory drugs
(NSAIDs).
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Irreversible steroid-induced ocular hypertension
/glaucoma
Medical antiglaucomatous therapy35
Miotics,
Beta-blockers, Prostaglandin analogues, Alpha
agonists, Carbonic anhydrase inhibitors
Argon laser trabeculoplasty (ALT)
Filtration surgery38
Glucocorticoid-Induced Diabetes Mellitus
The mechanism of glucocorticoid-induced diabetes
mellitus is multifactorial. Glucocorticoids induce
hepatic and extrahepatic insulin resistance.
Glucocorticoid treatment impairs both glucose
transport in fat and muscle cells and the ability of
glucose to stimulate its own utilization (glucose
effectiveness), as well as reducing glucose
clearance.
Treatment
Diet, Exercise, Self-monitoring of blood glucose
concentrations40
Patients with mild hyperglycemia (all blood
glucose concentrations <200 mg/dL)41
First-line treatment: metformin (at the
maximum tolerated dose, up to 2 g/day)
Second-line treatment: sulfonylureas,
meglitinides, or thiazolidenediones
Third-line treatment: single-dose neutral
protamine Hagedorn (NPH) insulin
Patients with fasting glucose concentration in
goal but other glucose concentrations e200
mg/dL42
NPH insulin or premixed (with rapid-acting
insulin) insulin once a day; start at a generous
dose (e.g., 0.2-0.4 units/kg per day)
May need another dose of rapid-acting insulin
with evening meal if bedtime blood glucose
concentrations are high
Patients with fasting and daytime blood
glucose concentrations e200 mg/dL43
Treat like any patient who newly requires
insulin but at a much higher starting dosage
(eg, 0.6-0.8 units/kg per day)
Patients often require a much larger proportion
of their insulin as prandial doses
CORTICOSTEROID-INDUCED PSYCHOSIS
Corticosteroid-induced psychosis represents a
spectrum of psychological changes that can occur
at any time during treatment. Mild-to-moderate
symptoms include agitation, anxiety, insomnia,
irritability, and restlessness, whereas severe
symptoms include mania, depression, and
psychosis 44
SPECTRUM OF PSYCHIATRICSYMPTOMS
Grading scale for corticosteroid-induced psychiatric symptoms
Grade Symptoms
Grade 1 Mild, nonpathologic, and subclinical euphoria
Grade 2 Reversible acute or subacute mania and/or depression
Grade 3 Bipolar disorder with relapses possible without steroids
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Pathophysiology of corticosteroid-induced
psychosis
How corticosteroids cause psychosis is not well
understood. One theory suggests that
corticosteroids act at steroid-specific receptors and
suppress filtering by the hippocampus of irrelevant
stimuli.50
Supporting this theory of hippocampal change, a
study of 17 patients receiving corticosteroid
therapy for >6 months found decreased
hippocampal volume compared with a control
group.51
Other possible causes include suppressed
hypothalamus-pituitary axis and enhanced
dopamine neurotransmission.52
Treatment
Management includes tapering corticosteroids, with
or without adding medications to treat the acute
state. Decreasing corticosteroids to the lowest dose
possible—<40 mg/d—or gradually discontinuing
therapy to prevent triggering adrenal insufficiency
may improve psychotic symptoms and avoids the
risk of adverse effects from adjunctive medications.
Psychopharmacologic treatment may be necessary,
depending on the severity of psychosis or the
underlying disease, particularly if corticosteroids
cannot be tapered or discontinued.45-49
CORTICOSTEROIDS INDUCED CUSHING’S
SYNDROME
Cushing’s syndrome describes the signs and
symptoms associated with prolonged exposure to
inappropriately high levels of the
hormone cortisol. This can be caused by
taking glucocorticoid drugs, or diseases that result
in excess cortisol, adrenocorticotropic
hormone (ACTH), or CRH levels.64
Pathophysiology
The hypothalamus is in the brain and the pituitary
gland sits just below it. The para ventricular
nucleus (PVN) of the hypothalamus
releases corticotropin-releasing hormone (CRH),
which stimulates the pituitary gland to release
adrenocorticotropin (ACTH). ACTH travels via the
blood to the adrenal gland, where it stimulates the
release of cortisol. Cortisol is secreted by the cortex
of the adrenal gland from a region called
the zonafasciculata in response to ACTH. Elevated
levels of cortisol exert negative feedback on the
pituitary, which decreases the amount of ACTH
released from the pituitary gland.
Strictly, Cushing's syndrome refers to excess
cortisol of any etiology (as Syndrome means a
group of symptoms). One of the causes of
Cushing's syndrome is a cortisol secreting adenoma
in the cortex of the adrenal gland
(primary hypercortisolism/ hypercorticism). The
adenoma causes cortisol levels in the blood to be
very high, and negative feedback on the pituitary
from the high cortisol levels causes ACTH levels to
be very low.
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Treatments and drugs53-62
Reducing corticosteroid use, Surgery, Radiation
therapy
Medications: Medications to control excessive
production of cortisol include ketoconazole,
mitotan and metyrapone. The Food and Drug
Administration has also approved the use of
mifepristone for people with Cushing syndrome
who have type 2 diabetes or glucose intolerance.
Mifepristone does not decrease cortisol production,
but it blocks the effect of cortisol on tissues.
CONCLUSION
Glucocorticoids play a major role in inducing
myopathy, osteoporosis, glaucoma, diabetes,
psychosis, cushing’s syndrome and various
pathological conditions. Although there has been
marked progress in the last few years in
understanding the mechanisms behind
corticosteroids induced disorders further research
needs to be undertaken. Physician managing
patients on corticosteroids should always consider
the need for therapy to prevent or treat
corticosteroids induced disorders. Better
identification of patients at risk of corticosteroids
induced disorders rises would allow them to be
more closely monitored than others. The entire
health care professionals should be aware of the
iatragenic disease management. Early detection of
these disorders can reduce the duration of hospital
stay and increase the quality of life.
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