The effects of diethylstilbestrol administration on rat kidney. ultrastructur...Prof. Hesham N. Mustafa
This study examined the effects of diethylstilbestrol (DES) administration on rat kidney tissues over different time periods using histological, immunohistochemical, and ultrastructural analysis. Thirty male rats were divided into three groups: a control group, a group that received 60 μg/kg DES daily for 20 days, and a group that received the same dose of DES for 50 days. DES administration for 50 days caused degeneration of renal tissues, damage to renal tubules, increased cellularity of glomeruli, and a significant increase in BAX protein expression, indicating increased apoptosis. These changes were less pronounced after 20 days of treatment. The study found that non-steroidal synthetic estrogens like DES can have
Protective effect of plants extracts mixture on sperm abnormalities, testicul...Alexander Decker
This study investigated the effects of diabetes mellitus type 2 (T2DM) on sperm abnormalities, testicular tissue, and epididymal tissue in male rats, and evaluated whether a mixture of extracts from five medicinal plants could reduce harm caused by diabetes. Rats were divided into groups: normal controls, diabetic controls, and diabetic rats treated with the plant extracts mixture for 45, 60, or 75 days. Diabetes increased sperm abnormalities and caused degenerative changes in testes and epididymis. Treatment with the plant extracts mixture significantly decreased most sperm abnormalities in diabetic rats and reduced degenerative changes in testes and epididymis tissues, showing protective effects against diabetes-related male reproductive harm.
1) The study evaluated the effect of living unrelated donor bone marrow cell infusion on kidney allograft function in 40 kidney transplant patients, with 20 receiving concurrent bone marrow infusion and 20 receiving transplant alone.
2) Mean serum creatinine levels were similar between the two groups at 2 weeks and between 3 weeks to 7 months post-transplant.
3) Rates of acute rejection, delayed graft function, and use of anti-thymocyte globulin were similar between the two groups, though clinical presentations of rejection seemed more severe in the control group without bone marrow infusion.
RELIEF BEYOND EXPECTATIONS ARTHRITIS TREATMENT USING YOUR OWN STEM CELLS Dr. ...Lifecare Centre
This document describes stem cell therapy for osteoarthritis offered by Global Stemgenn in Delhi, India. It outlines how stem cells derived from a patient's own bone marrow, fat, or blood can be used to regenerate cartilage and relieve pain, providing an alternative to joint replacement surgery. The therapy is presented as minimally invasive, with most patients experiencing over 90% pain relief within 3 months and evidence of cartilage healing after 1 year. Testimonials from grateful patients are provided. The document discusses the safety, efficacy and costs of the treatment.
A double-blind, randomized, placebo-controlled study found that consumption of StemEnhance (SE) led to a 24-30% increase in circulating stem cells compared to placebo. SE significantly increased the number of CD34+ stem cells in blood samples taken 30-120 minutes after ingestion. This increase corresponded to approximately 3.5 million new circulating stem cells in the bloodstream, which studies suggest could result in billions of new cells in target tissues and may have physiological relevance.
This document summarizes different methods of kidney preservation for transplantation, including static cold storage and hypothermic machine perfusion. Static cold storage has traditionally been the main method, involving cooling and storing kidneys in preservation solutions. However, machine perfusion may provide advantages like reducing delayed graft function, especially for expanded criteria donors. While both methods aim to minimize damage during cold storage, machine perfusion allows monitoring and restoring organ viability before transplantation. Future areas of research include evaluating marginal kidneys and predicting transplant outcomes through biomarkers and other machine perfusion techniques.
The role of curcumin in streptozotocin induced hepatic damage and the trans-d...Prof. Hesham N. Mustafa
Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.
This document describes a new bioartificial pancreas (BAP) device called "b-Air" that is designed to overcome challenges with islet transplantation, specifically inadequate oxygen supply and protection from the host immune system. The b-Air consists of islets immobilized in an alginate hydrogel within a gas chamber that can be supplied with oxygen via subdermal ports. In animal studies, the b-Air completely normalized blood glucose and HbA1c levels in diabetic rats for up to 6 months. The device was dependent on oxygen supply and provided immune protection by allowing survival of both isografts and allografts. Explanted devices showed intact, functional islets without inflammation. Increased islet loading
The effects of diethylstilbestrol administration on rat kidney. ultrastructur...Prof. Hesham N. Mustafa
This study examined the effects of diethylstilbestrol (DES) administration on rat kidney tissues over different time periods using histological, immunohistochemical, and ultrastructural analysis. Thirty male rats were divided into three groups: a control group, a group that received 60 μg/kg DES daily for 20 days, and a group that received the same dose of DES for 50 days. DES administration for 50 days caused degeneration of renal tissues, damage to renal tubules, increased cellularity of glomeruli, and a significant increase in BAX protein expression, indicating increased apoptosis. These changes were less pronounced after 20 days of treatment. The study found that non-steroidal synthetic estrogens like DES can have
Protective effect of plants extracts mixture on sperm abnormalities, testicul...Alexander Decker
This study investigated the effects of diabetes mellitus type 2 (T2DM) on sperm abnormalities, testicular tissue, and epididymal tissue in male rats, and evaluated whether a mixture of extracts from five medicinal plants could reduce harm caused by diabetes. Rats were divided into groups: normal controls, diabetic controls, and diabetic rats treated with the plant extracts mixture for 45, 60, or 75 days. Diabetes increased sperm abnormalities and caused degenerative changes in testes and epididymis. Treatment with the plant extracts mixture significantly decreased most sperm abnormalities in diabetic rats and reduced degenerative changes in testes and epididymis tissues, showing protective effects against diabetes-related male reproductive harm.
1) The study evaluated the effect of living unrelated donor bone marrow cell infusion on kidney allograft function in 40 kidney transplant patients, with 20 receiving concurrent bone marrow infusion and 20 receiving transplant alone.
2) Mean serum creatinine levels were similar between the two groups at 2 weeks and between 3 weeks to 7 months post-transplant.
3) Rates of acute rejection, delayed graft function, and use of anti-thymocyte globulin were similar between the two groups, though clinical presentations of rejection seemed more severe in the control group without bone marrow infusion.
RELIEF BEYOND EXPECTATIONS ARTHRITIS TREATMENT USING YOUR OWN STEM CELLS Dr. ...Lifecare Centre
This document describes stem cell therapy for osteoarthritis offered by Global Stemgenn in Delhi, India. It outlines how stem cells derived from a patient's own bone marrow, fat, or blood can be used to regenerate cartilage and relieve pain, providing an alternative to joint replacement surgery. The therapy is presented as minimally invasive, with most patients experiencing over 90% pain relief within 3 months and evidence of cartilage healing after 1 year. Testimonials from grateful patients are provided. The document discusses the safety, efficacy and costs of the treatment.
A double-blind, randomized, placebo-controlled study found that consumption of StemEnhance (SE) led to a 24-30% increase in circulating stem cells compared to placebo. SE significantly increased the number of CD34+ stem cells in blood samples taken 30-120 minutes after ingestion. This increase corresponded to approximately 3.5 million new circulating stem cells in the bloodstream, which studies suggest could result in billions of new cells in target tissues and may have physiological relevance.
This document summarizes different methods of kidney preservation for transplantation, including static cold storage and hypothermic machine perfusion. Static cold storage has traditionally been the main method, involving cooling and storing kidneys in preservation solutions. However, machine perfusion may provide advantages like reducing delayed graft function, especially for expanded criteria donors. While both methods aim to minimize damage during cold storage, machine perfusion allows monitoring and restoring organ viability before transplantation. Future areas of research include evaluating marginal kidneys and predicting transplant outcomes through biomarkers and other machine perfusion techniques.
The role of curcumin in streptozotocin induced hepatic damage and the trans-d...Prof. Hesham N. Mustafa
Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.
This document describes a new bioartificial pancreas (BAP) device called "b-Air" that is designed to overcome challenges with islet transplantation, specifically inadequate oxygen supply and protection from the host immune system. The b-Air consists of islets immobilized in an alginate hydrogel within a gas chamber that can be supplied with oxygen via subdermal ports. In animal studies, the b-Air completely normalized blood glucose and HbA1c levels in diabetic rats for up to 6 months. The device was dependent on oxygen supply and provided immune protection by allowing survival of both isografts and allografts. Explanted devices showed intact, functional islets without inflammation. Increased islet loading
This study aimed to investigate using reticulocyte hemoglobin equivalent (RetHe) measurement and serum hepcidin level to differentiate iron deficiency anemia (IDA) from anemia of chronic disease (ACD), with the goal of reducing the number of tests required. The study analyzed data from 77 subjects and found that a serum ferritin level of 30μg/L differentiated IDA and ACD with reasonable sensitivity and specificity. A serum hepcidin level of 40ng/mL also differentiated the conditions, though with lower specificity for IDA. For subjects with mixed etiology, RetHe helped identify those likely to respond to iron therapy. The study concludes that using RetHe and serum hepcidin could reduce the diagnostic
Cirrhosis results from different mechanisms of liver injury that lead to necroinflammation and fibrogenesis; Patients
with liver cirrhosis often require liver transplantation but it is affected by many problems, including relative operative
damage, high costs, lack of donors, and risk of rejection. Currently studies are shown the Stem cell therapy has the
potential to provide a valuable adjunct to the management of disease, Stem cell should be the natural candidates to
provide a renewable source of cells for transplantation.
The main mechanism of stem cell therapy is that stem cell capacity to differentiate into any of the hundreds of distinct
cell types that comprise the human body. In addition to their potential in therapeutics can be used to study the earliest
stages of human development and disease modeling using human cells.
Keywords: Cell Therapy; Liver Cirrhosis; Stem Cell; Transplantation. limitlessly, and often play the principal role in
liver regeneration
Background: Body of literature are becoming pronounced that pathological condition in one organ of the body might have an effect on other distal organs owing to the fact, that the entire body metabolism is orchestrated centrally.
Pathological events occurring in an organ are likely to be extended to other organs. Pretreatment that minimize these events are presumed to be beneficial to the extended organs.
Methods: Following 30 min of ischemia and 48 h of reperfusion in the kidney, rats under anesthesia were sacrificed and blood sample collected through cardiac puncture. Serum level of troponin I, and activities of total creatine kinase (CK), mass creatine kinase (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma –glutamyl transferase (GGT) were estimated spectrophotometrically.
Results: Serum troponin I increased to 0.031 ± 0.001 ng/ml in the ischemic group, and following pretreatment with Lmm (600mg/kg), serum level of troponin I decreased significantly to 0.021 ± 0.001 ng/ml (P<.05).><.05),><.05)><.05).
Endothelial surface layer degradation by chronicmarconou1
This study investigated the effects of degrading the endothelial surface layer (ESL) in apolipoprotein E-deficient (apoE-/-) mice, an atherosclerosis model, through chronic hyaluronidase infusion. Key findings:
1) Hyaluronidase infusion decreased the ESL volume and plasma volume in apoE-/- mice compared to inactive hyaluronidase.
2) Active hyaluronidase increased proteinuria without changes in renal morphology, suggesting ESL degradation impacts the glomerular barrier.
3) Atherosclerotic plaques in hyaluronidase-treated mice showed increased matrix production and compositional changes, pointing to increased plaque vulnerability.
4)
Wilmore Labs is seeking $350,000 for a mid-size pre-clinical study to prove the effectiveness of their buccal delivery of resveratrol. Resveratrol is a proven vasodilator that could potentially treat angina, atherosclerotic cardiovascular disease, peripheral artery disease, and erectile dysfunction. Their buccal lozenge formulation has shown success in initial bench tests and human studies, achieving therapeutic resveratrol levels faster than oral dosing without gastrointestinal side effects. The funding would allow further pre-clinical testing before pursuing FDA approval and clinical trials.
il dottor Spoliti Ortopedico illustra come curare con le Cellule mesenchimali, difetto condrale Ricostruzione con Acido Ialuronico e midollo osseo autologo Aspirare Concentrate
Veropaque, a novel contrast agent containing iohexol and a substituted cyclodextrin (SCD), was shown to significantly reduce contrast-induced acute kidney injury (CI-AKI) in preclinical studies compared to iohexol alone. In mouse and rat models, Veropaque demonstrated reduced kidney pathology scores and preserved kidney function as measured by plasma creatinine levels. A dog study found Veropaque caused no differences in cardiovascular effects from intracoronary injection of iohexol alone. The SCD was able to protect the kidney from multiple contrast agents, suggesting a mechanism beyond complexation of the contrast. Based on these findings, the authors believe Veropaque has potential to decrease CI-AKI
This document summarizes a research project investigating the role of the Farnesoid X Receptor (FXR) in nonalcoholic steatohepatitis (NASH). The objective was to determine how FXR impacts NASH by studying mice with FXR "knocked out" in the liver, intestine, or both when fed a high fat diet. Results showed knockout groups developed signs of NASH like wildtype mice on the diet, with liver knockout mice most severely affected. However, immunohistochemistry staining for FXR and BSEP proteins was inconclusive. Future work could examine bile acid levels and mechanisms of FXR regulating inflammation, and replicate with a shorter study to test for acute effects.
Role of Plasma Exchange in ABO-incompatible Kidney TransplantationApollo Hospitals
In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However,
multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection.
This case report summarizes a 49-year-old man who presented with chronic low back pain, numbness in his legs, muscle weakness, and other symptoms. Examinations found osteopenia, compression fractures in his spine, and spondylolisthesis. He was diagnosed with osteoporosis likely caused by long-term glucocorticoid use, alcohol consumption, and a recent fall. He was prescribed calcium, vitamin D, medications to treat osteoporosis and prevent further fractures, and referred to a neurologist for further evaluation of possible lumbar disc herniation.
Am j physiol heart circ physiol 2000-matsubara-h1534-9Natasha Xavier
This document reports on a study investigating the influence of myocardial collagen content on rat papillary muscle function. Three groups of rats were studied: 1) a renal hypertension group with increased collagen (RHTR), 2) a group with decreased collagen through glutathione infusion (GSSG), and 3) untreated controls. The main findings were:
1) GSSG rats had increased active stiffness and myocyte size compared to controls, suggesting decreased collagen is related to hypertrophy and increased active stiffness.
2) Passive tension-length curves were shifted down in GSSG rats, indicating decreased passive stiffness, and up in RHTR rats, indicating increased passive stiffness.
3) Changes in collagen content bidirectionally influence
This study aimed to identify markers of cellular senescence in injured kidney tissue using imaging mass cytometry (IMC). Human kidney cells (HK-2 cells) were treated with cyclosporine A (Cs-A) to induce senescence, then stained with an anti-p21 antibody. The p21 antibody signal increased with Cs-A treatment and was localized to the cell cytoplasm. Future work will include validating increased p21 expression through PCR and western blotting. The goal is to use IMC to detect p21 in injured and control human kidney biopsy samples to better understand acute kidney injury and senescence.
Rutger Ploeg - The Netherlands - Tuesday 29 -Experience in DCD Programs logi...incucai_isodp
The document discusses improving organ transplantation outcomes by focusing on donor organ preservation techniques. It notes that without improvements, transplantation may become limited. It reviews research showing machine perfusion reduces injury compared to cold storage for donation after cardiac death kidneys. Future areas of focus include better donor organ selection and protection from ischemia-reperfusion injury through continuous perfusion and repair strategies in both donors and recipients. The goal is to make currently untransplantable organs transplantable through protective interventions.
This clinical study compared bone mineral density (BMD) and body proportions in women with complete androgen insensitivity syndrome (CAIS) and gonadal dysgenesis (GD). It found that women with CAIS were taller than women with GD(XX) but shorter than women with GD(XY). Women with GD(XY) had a greater lower to upper body ratio than women with CAIS, suggesting greater estrogen deficiency in puberty. Women with GD(XY) were over 5 times more likely to have low hip BMD compared to women with CAIS, indicating androgen plays an important role in bone mineralization in women with CAIS.
Xuhui Liu is an experienced physician-scientist specializing in biomedical research. He has over 20 years of experience conducting clinical and preclinical research focused on musculoskeletal and neurological diseases. Currently, he is an Associate Professor at UCSF leading research programs in bone health, rotator cuff injuries, and neuro-musculoskeletal trauma. He has published over 30 peer-reviewed papers and is an active reviewer for several academic journals.
The study examined the effects of combining alendronate (ALN), a bisphosphonate, with human parathyroid hormone (PTH) administered daily or cyclically on bone strength in mice. Mice were treated with ALN alone, PTH alone daily or cyclically, or combinations of ALN and PTH daily or cyclically. Bone mineral density, structure, strength, and markers were measured after 7 weeks. The results showed that combinations of ALN and PTH, both daily and cyclically, produced greater increases in bone mineral density and strength than either treatment alone, indicating complementary mechanisms of action. PTH and ALN had synergistic effects on bone strength in the lumbar vertebrae and additive
This study investigated the effects of hyperbaric oxygen (HBO) exposure on oxidative stress in rats with streptozotocin-induced diabetes. Rats were divided into four groups: non-diabetic no HBO, non-diabetic with HBO, diabetic no HBO, and diabetic with HBO. Diabetes was induced with streptozotocin. HBO groups received 2.8 ATA oxygen for 2 hours daily for 7 days. The study found that HBO exposure increased blood glucose levels and lipid peroxidation while decreasing antioxidant enzyme activity in diabetic rats. This suggested that HBO exposure may exacerbate oxidative stress in diabetes through increased reactive oxygen species production.
Pathophysiological mechanisms and consequences of gut edema (Annika Reintam W...WSACS
Gut edema in acute illness is not yet sufficiently studied and existing knowledge is largely based on experimental animal studies or small studies in healthy volunteers. However, increasing evidence confirms that gut edema impairs intestinal motility and healing of bowel anastomoses, being therefore an important contributor to outcome.
Current presentation focuses mainly on the role of fluids in development of intestinal edema.
This document discusses emerging restorative therapies for erectile dysfunction including shockwave therapy, stem cells, and platelet-rich plasma injections. It provides an overview of the proposed mechanisms of action and current evidence from studies on each therapy. While initial studies show promise, the document concludes that more rigorous randomized controlled trials are still needed to establish efficacy and safety before these therapies can be considered non-experimental options for treating erectile dysfunction.
This study aimed to investigate using reticulocyte hemoglobin equivalent (RetHe) measurement and serum hepcidin level to differentiate iron deficiency anemia (IDA) from anemia of chronic disease (ACD), with the goal of reducing the number of tests required. The study analyzed data from 77 subjects and found that a serum ferritin level of 30μg/L differentiated IDA and ACD with reasonable sensitivity and specificity. A serum hepcidin level of 40ng/mL also differentiated the conditions, though with lower specificity for IDA. For subjects with mixed etiology, RetHe helped identify those likely to respond to iron therapy. The study concludes that using RetHe and serum hepcidin could reduce the diagnostic
Cirrhosis results from different mechanisms of liver injury that lead to necroinflammation and fibrogenesis; Patients
with liver cirrhosis often require liver transplantation but it is affected by many problems, including relative operative
damage, high costs, lack of donors, and risk of rejection. Currently studies are shown the Stem cell therapy has the
potential to provide a valuable adjunct to the management of disease, Stem cell should be the natural candidates to
provide a renewable source of cells for transplantation.
The main mechanism of stem cell therapy is that stem cell capacity to differentiate into any of the hundreds of distinct
cell types that comprise the human body. In addition to their potential in therapeutics can be used to study the earliest
stages of human development and disease modeling using human cells.
Keywords: Cell Therapy; Liver Cirrhosis; Stem Cell; Transplantation. limitlessly, and often play the principal role in
liver regeneration
Background: Body of literature are becoming pronounced that pathological condition in one organ of the body might have an effect on other distal organs owing to the fact, that the entire body metabolism is orchestrated centrally.
Pathological events occurring in an organ are likely to be extended to other organs. Pretreatment that minimize these events are presumed to be beneficial to the extended organs.
Methods: Following 30 min of ischemia and 48 h of reperfusion in the kidney, rats under anesthesia were sacrificed and blood sample collected through cardiac puncture. Serum level of troponin I, and activities of total creatine kinase (CK), mass creatine kinase (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma –glutamyl transferase (GGT) were estimated spectrophotometrically.
Results: Serum troponin I increased to 0.031 ± 0.001 ng/ml in the ischemic group, and following pretreatment with Lmm (600mg/kg), serum level of troponin I decreased significantly to 0.021 ± 0.001 ng/ml (P<.05).><.05),><.05)><.05).
Endothelial surface layer degradation by chronicmarconou1
This study investigated the effects of degrading the endothelial surface layer (ESL) in apolipoprotein E-deficient (apoE-/-) mice, an atherosclerosis model, through chronic hyaluronidase infusion. Key findings:
1) Hyaluronidase infusion decreased the ESL volume and plasma volume in apoE-/- mice compared to inactive hyaluronidase.
2) Active hyaluronidase increased proteinuria without changes in renal morphology, suggesting ESL degradation impacts the glomerular barrier.
3) Atherosclerotic plaques in hyaluronidase-treated mice showed increased matrix production and compositional changes, pointing to increased plaque vulnerability.
4)
Wilmore Labs is seeking $350,000 for a mid-size pre-clinical study to prove the effectiveness of their buccal delivery of resveratrol. Resveratrol is a proven vasodilator that could potentially treat angina, atherosclerotic cardiovascular disease, peripheral artery disease, and erectile dysfunction. Their buccal lozenge formulation has shown success in initial bench tests and human studies, achieving therapeutic resveratrol levels faster than oral dosing without gastrointestinal side effects. The funding would allow further pre-clinical testing before pursuing FDA approval and clinical trials.
il dottor Spoliti Ortopedico illustra come curare con le Cellule mesenchimali, difetto condrale Ricostruzione con Acido Ialuronico e midollo osseo autologo Aspirare Concentrate
Veropaque, a novel contrast agent containing iohexol and a substituted cyclodextrin (SCD), was shown to significantly reduce contrast-induced acute kidney injury (CI-AKI) in preclinical studies compared to iohexol alone. In mouse and rat models, Veropaque demonstrated reduced kidney pathology scores and preserved kidney function as measured by plasma creatinine levels. A dog study found Veropaque caused no differences in cardiovascular effects from intracoronary injection of iohexol alone. The SCD was able to protect the kidney from multiple contrast agents, suggesting a mechanism beyond complexation of the contrast. Based on these findings, the authors believe Veropaque has potential to decrease CI-AKI
This document summarizes a research project investigating the role of the Farnesoid X Receptor (FXR) in nonalcoholic steatohepatitis (NASH). The objective was to determine how FXR impacts NASH by studying mice with FXR "knocked out" in the liver, intestine, or both when fed a high fat diet. Results showed knockout groups developed signs of NASH like wildtype mice on the diet, with liver knockout mice most severely affected. However, immunohistochemistry staining for FXR and BSEP proteins was inconclusive. Future work could examine bile acid levels and mechanisms of FXR regulating inflammation, and replicate with a shorter study to test for acute effects.
Role of Plasma Exchange in ABO-incompatible Kidney TransplantationApollo Hospitals
In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However,
multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection.
This case report summarizes a 49-year-old man who presented with chronic low back pain, numbness in his legs, muscle weakness, and other symptoms. Examinations found osteopenia, compression fractures in his spine, and spondylolisthesis. He was diagnosed with osteoporosis likely caused by long-term glucocorticoid use, alcohol consumption, and a recent fall. He was prescribed calcium, vitamin D, medications to treat osteoporosis and prevent further fractures, and referred to a neurologist for further evaluation of possible lumbar disc herniation.
Am j physiol heart circ physiol 2000-matsubara-h1534-9Natasha Xavier
This document reports on a study investigating the influence of myocardial collagen content on rat papillary muscle function. Three groups of rats were studied: 1) a renal hypertension group with increased collagen (RHTR), 2) a group with decreased collagen through glutathione infusion (GSSG), and 3) untreated controls. The main findings were:
1) GSSG rats had increased active stiffness and myocyte size compared to controls, suggesting decreased collagen is related to hypertrophy and increased active stiffness.
2) Passive tension-length curves were shifted down in GSSG rats, indicating decreased passive stiffness, and up in RHTR rats, indicating increased passive stiffness.
3) Changes in collagen content bidirectionally influence
This study aimed to identify markers of cellular senescence in injured kidney tissue using imaging mass cytometry (IMC). Human kidney cells (HK-2 cells) were treated with cyclosporine A (Cs-A) to induce senescence, then stained with an anti-p21 antibody. The p21 antibody signal increased with Cs-A treatment and was localized to the cell cytoplasm. Future work will include validating increased p21 expression through PCR and western blotting. The goal is to use IMC to detect p21 in injured and control human kidney biopsy samples to better understand acute kidney injury and senescence.
Rutger Ploeg - The Netherlands - Tuesday 29 -Experience in DCD Programs logi...incucai_isodp
The document discusses improving organ transplantation outcomes by focusing on donor organ preservation techniques. It notes that without improvements, transplantation may become limited. It reviews research showing machine perfusion reduces injury compared to cold storage for donation after cardiac death kidneys. Future areas of focus include better donor organ selection and protection from ischemia-reperfusion injury through continuous perfusion and repair strategies in both donors and recipients. The goal is to make currently untransplantable organs transplantable through protective interventions.
This clinical study compared bone mineral density (BMD) and body proportions in women with complete androgen insensitivity syndrome (CAIS) and gonadal dysgenesis (GD). It found that women with CAIS were taller than women with GD(XX) but shorter than women with GD(XY). Women with GD(XY) had a greater lower to upper body ratio than women with CAIS, suggesting greater estrogen deficiency in puberty. Women with GD(XY) were over 5 times more likely to have low hip BMD compared to women with CAIS, indicating androgen plays an important role in bone mineralization in women with CAIS.
Xuhui Liu is an experienced physician-scientist specializing in biomedical research. He has over 20 years of experience conducting clinical and preclinical research focused on musculoskeletal and neurological diseases. Currently, he is an Associate Professor at UCSF leading research programs in bone health, rotator cuff injuries, and neuro-musculoskeletal trauma. He has published over 30 peer-reviewed papers and is an active reviewer for several academic journals.
The study examined the effects of combining alendronate (ALN), a bisphosphonate, with human parathyroid hormone (PTH) administered daily or cyclically on bone strength in mice. Mice were treated with ALN alone, PTH alone daily or cyclically, or combinations of ALN and PTH daily or cyclically. Bone mineral density, structure, strength, and markers were measured after 7 weeks. The results showed that combinations of ALN and PTH, both daily and cyclically, produced greater increases in bone mineral density and strength than either treatment alone, indicating complementary mechanisms of action. PTH and ALN had synergistic effects on bone strength in the lumbar vertebrae and additive
This study investigated the effects of hyperbaric oxygen (HBO) exposure on oxidative stress in rats with streptozotocin-induced diabetes. Rats were divided into four groups: non-diabetic no HBO, non-diabetic with HBO, diabetic no HBO, and diabetic with HBO. Diabetes was induced with streptozotocin. HBO groups received 2.8 ATA oxygen for 2 hours daily for 7 days. The study found that HBO exposure increased blood glucose levels and lipid peroxidation while decreasing antioxidant enzyme activity in diabetic rats. This suggested that HBO exposure may exacerbate oxidative stress in diabetes through increased reactive oxygen species production.
Pathophysiological mechanisms and consequences of gut edema (Annika Reintam W...WSACS
Gut edema in acute illness is not yet sufficiently studied and existing knowledge is largely based on experimental animal studies or small studies in healthy volunteers. However, increasing evidence confirms that gut edema impairs intestinal motility and healing of bowel anastomoses, being therefore an important contributor to outcome.
Current presentation focuses mainly on the role of fluids in development of intestinal edema.
This document discusses emerging restorative therapies for erectile dysfunction including shockwave therapy, stem cells, and platelet-rich plasma injections. It provides an overview of the proposed mechanisms of action and current evidence from studies on each therapy. While initial studies show promise, the document concludes that more rigorous randomized controlled trials are still needed to establish efficacy and safety before these therapies can be considered non-experimental options for treating erectile dysfunction.
Evaluation of the Hepa Wash treatment in pigs with acute liver failureEnrique Moreno Gonzalez
This document summarizes a study that evaluated a new liver support treatment called Hepa Wash in pigs with acute liver failure. Pigs underwent surgery to induce acute liver failure and were randomly assigned to either a control group or a Hepa Wash treatment group. The Hepa Wash group showed significantly higher survival rates and improvements in organ function compared to controls. A separate pilot study also found improvements in pigs treated with another liver support system called MARS. The results suggest Hepa Wash may be a safe and effective treatment for acute liver failure.
This study investigated how the differentiation of hematopoietic stem cells (HSCs) is affected by the transplantation dose. The researchers found that:
1) At high transplantation doses, more donor HSCs engrafted and produced all measured blood cell types (granulocytes, B cells, CD4 T cells, CD8 T cells), compared to low doses.
2) At 4 months post-transplantation, 70-80% of HSC clones only produced one or two blood cell types ("specialized"), rather than all types, as previously thought.
3) High doses led to more HSC clones with balanced lymphocyte production, while low doses produced more clones specialized in T
HBOT: an essential component for the regenerative treatment of pain from spor...Megan Hughes
The document discusses how hyperbaric oxygen therapy (HBOT) can help treat chronic pain by promoting cellular autophagy which reduces inflammation, it can aid in sports injury recovery by enhancing tissue growth and stem cell circulation, and HBOT combined with intravenous stem cell therapies may help regenerate tissues damaged by conditions like traumatic brain injuries or arthritis.
1. Continuous CSF sampling studies are generally well tolerated, with the most common adverse events being post-dural puncture headache and back pain.
2. Some patient groups, such as females, the elderly, and those with mood disorders, report a higher frequency of adverse events.
3. Factors such as larger CSF needle size, higher CSF volumes removed, and multiple sampling periods increased adverse event rates, while smaller needle sizes reduced adverse events.
4. CSF sampling windows of 26-36 hours were equally tolerated, and a 14-day interval between repeated sampling allowed for good tolerability.
dkNET Webinar "The Multi-Omic Response to Exercise Training Across Rat Tissue...dkNET
Presenter: Malene Lindholm, PhD, Instructor, Department of Medicine, Stanford University
Abstract
The Molecular Transducers of Physical Activity Consortium (MoTrPAC) aims to map the molecular responses to exercise and training to elucidate how exercise improves health and prevents disease. The first MoTrPAC data provides an extensive temporal map of the dynamic multi-omic response to endurance training across multiple rat tissues. All results can be viewed, interrogated, and downloaded in a user-friendly, publicly accessible data portal (https://motrpac-data.org). The MoTrPAC data compendium includes transcriptomics, proteomics, metabolomics, phosphoproteomics, acetylproteomics, ubiquitylproteomics, DNA methylation, chromatin accessibility, and multiplexed immunoassay data. This compilation constitutes of 211 datasets across 19 tissues, 25 molecular assays, and 4 training time points in adult male and female rats. Over 35,000 analytes were found to be differentially regulated in response to endurance training, with many displaying sexual dimorphism. We observed a male-specific recruitment of immune cells to adipose tissues and an anticorrelated transcriptional response in the adrenal gland related to the stress response. Temporal multi-omic and multi-tissue integration demonstrated similar temporal responses in the heart and skeletal muscle, reflecting a concerted adaptation of mitochondrial biogenesis and metabolism. Integrative multi-omic network analysis revealed connections between the heat shock-mediated stress response and mitochondrial biogenesis. Training increased phospholipids and decreased triacylglycerols in the liver, and there were extensive changes to mitochondrial protein acetylation. Many changes were relevant for human health conditions, such as non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular wellness, and tissue damage and repair. Altogether, this MoTrPAC resource provides an unprecedented view of the effects of exercise across an organism, revealing mechanistic details of how exercise impacts mammalian health. The MoTrPAC data hub is the primary online resource to disseminate this large-scale multi-omics data.
The top 3 questions that the MoTrPAC resource can answer:
1. What is the multi-omic response to endurance exercise across different tissues?
2. What are the top signaling pathways affected in response to exercise and do they differ between males and females?
3. How can the MoTrPAC data hub be utilized to interrogate all the MoTrPAC findings?
Upcoming webinars schedule: https://dknet.org/about/webinar
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Wiedermann - How does hes accumulate in the tissues
1. How does HES accumulate
in the tissues?
Christian J. Wiedermann, MD
Central Hospital of Bolzano, Italy
2. Characteristics of Hydroxyethyl Starch
(HES) Storage in Human Tissues
• Rapid
• Widespread
• Cumulative
• Long-Lasting
HES-laden intracytoplasmic vacuole detected
within 90 min after single 30 g HES infusion
by immunoelectron microscopy with anti-HES
antibody in skin perivascular histiocyte.
Ständer et al. Cell Tissue Res 304:261-9, 2001.
3. Human Tissue Sites of HES Storage
Pfeifer et al. Klin Wochenschr 62:862-6, 1984.
Sirtl et al. Beitr Anaesth Intensivmed 26:74-97, 1988.
Heilmann et al. Infusionstherapie 18:236-43, 1991.
Jurecka et al. Arch Dermatol Res 285:13-9, 1993.
Szeimies et al. Br J Dermatol 131:380-2, 1994.
Metze et al. Br J Dermatol 136:553-9, 1997.
Sirtl et al. Br J Anaesth 82:510-5, 1999.
Christidis et al. J Hepatol 35:726-32, 2001.
Auwerda et al. Ann Intern Med 137:1013-4, 2002.
Nohé et al. Eur Surg Res 34:364-72, 2002.
4. HES Stored in Diverse Parenchymal and
Reticuloendothelial Human Cell Types
Szépfalusi et al: Arch Dermatol Res 285:144-50, 1993.
Metze et al: Br J Dermatol 136:553-9, 1997.
Christidis et al: J Hepatol 35:726-32, 2001.
Ständer et al: Cell Tissue Res 304:261-9, 2001.
Proximal Renal
Tubular Cells
Kupffer Cells
Hepatocytes
Vascular
Endothelial
Cells
Keratinocytes
Secretory
Epithelial Cells
Peripheral
Neurons
Schwann Cells
Perineural
Cells
Macrophages Monocytes
Perivacular
Histiocytes
Auwerda et al: Ann Intern Med 137:1013-4, 2002.
Nohé et al: Eur Surg Res 34:364-72, 2002.
Weisshaar et al: Hautarzt 55:558-61, 2004.
Ebcioglu et al: Kidney Int 70:1873-6, 2006.
5. Pfeifer et al. Klin Wochenschr 62:862-6, 1984.
Ständer et al. Cell Tissue Res 304:261-9, 2001.
Quantity Stored in Human Cells Increases
with Cumulative HES Dose
• HES storage can reach massive levels
– Liver tissue HES concentration of 4% w/w reported
6. Quantitative Accumulation of HES in Major
Organs after Repeated Infusions
Lukäsewitz et al: J Anaesth Intensivbeh 3:42-6, 1998.
Necropsy study of 12 young adults
who died of sepsis and multi-organ
failure after repeated infusions of
HES 200/0.5
7. Sirtl et al. Br J Anaesth 82:510-5, 1999.
Pillebout et al. Am J Transplant 5:1120-9, 2005.
Long-Lasting Storage of HES
in Human Tissues
• No known intracellular enzymes able to catabolize HES
– HES can persist indefinitely in long-lived cell types
– Still detectable after up to 10 years or more in kidney,
> 4 years in skin and > 1 year in intestine and muscle
HES observed in 16 of 26 (61%)
orthotopic liver transplant patients by
renal biopsy a mean of 5 years after
HES exposure
8. Dual Routes of HES Endocytosis
Szépfalusi et al. Arch Dermatol Res 285:144-50, 1993.
Nohé et al. Eur Surg Res 34:364-72, 2002.
9. Nohé et al. Eur Surg Res 34:364-72, 2002.
Pinocytosis of HES
Untreated cultured human
vascular endothelial cells
HES-laden lysosomes after
incubation with HES 200/0.5
10. Schmidt-Hieber et al. Eur J Haematol 77:83-5, 2006.
Phagocytosis of HES
Foamy portal macrophages and
Kupffer cells in liver biopsy of
patient with liver failure and
myelosuppression after
cumulative 1200 g HES 130/0.4
and HES 200/0.5.
Foamy cell degenerated
macrophages comprising ~50%
of nucleated cells in bone
marrow biopsy of same patient.
11. Westphal et al: Anesthesiology 111:187-202, 2009.
Does Rapid Plasma Clearance
of HES Affect Storage?
• HES comprises polydisperse mixture of molecules
– Differing mean molecular weight (MW)
– Differing degree of molar substitution (MS)
• Four categories based on MS
– Tetrastarch (eg HES 130/0.4)
– Pentastarch (eg HES 200/0.5)
– Hexastarch (eg HES 200/0.62
– Hetastarch (eg HES 450/0.7)
• Tetrastarch and Pentastarch more rapidly cleared
from plasma
12. Bellmann et al: Clin Pharmacokinet 51:225-36, 2012.
Meta-Analysis of HES Tissue
Uptake in Clinical Studies
• 25 clinical studies with 287 total subjects
– Most studies of healthy volunteers
• Urine, plasma and tissue HES 24 h after single infusion
– Tissue uptake of HES determined indirectly
– Tissue HES = HES Dose – Urine HES – Plasma HES
• Tissue uptake of different HES types compared
13. Percent of HES Dose in Tissue at 24 h
Tetrastarch 9 92 42.3 (36.8-47.7)
Pentastarch 11 84 42.5 (39.2-45.8)
Hexastarch 2 11 31.7 (24.6-38.7)
Hetastarch 11 131 25.6 (18.3-32.9)
HES Type Groups Subjects Tissue % (CI)
Pooled tissue uptake of Tetrastarch/Pentastarch (42.4%) higher
by 15.8% (p < 0.001) vs Hexastarch/Hetastarch (26.6%).
Bellmann et al: Clin Pharmacokinet 51:225-36, 2012.
14. Factors Affecting Tissue Uptake of HES
Year Reported ≤ 2000 vs > 2000 0.22
Subjects per Group ≤ 6 vs > 6 0.91
Type of Subjects Healthy Volunteers vs Patients 0.07
Preinfusion Volume Status Euvolemic vs Hypovolemic 0.96
HES Molecular Weight (kD) ≤ 200 vs > 200 < 0.001
HES Molar Substitution ≤ 0.5 vs > 0.5 < 0.001
HES C2:C6 Ratio ≤ 6 vs > 6 0.21
HES Concentration (%) 6 vs 10 vs 14 0.20
HES Volume Infused (mL) ≤ 500 vs > 500 0.26
HES Dose (g) ≤ 50 vs > 50 0.29
Factor Comparison p
Conclusion: Only HES MW and MS mattered.
Bellmann et al: Clin Pharmacokinet 51:225-36, 2012.
15. Adverse Effects of HES Associated
with Tissue Storage
• Kidney Injury
– HES increased recourse to renal replacement
therapy (RRT) in multiple recent meta-analyses of
randomized controlled trials (RCTs)
• Liver Failure
– HES increased liver failure in a large recent RCT
• Pruritus
– HES increased pruritus in a recent meta-analysis of
RCTs
Myburgh et al. N Engl J Med 367:1901-11, 2012.
Zarychanski et al. JAMA 309:678-88, 2013.
Gattas et al. Intensive Care Med DOI 10.1007/s00134-013-2840-0, 2013.
Haase et al. BMJ 346:f839 doi: 10.1136/bmj.f839, 2013.
Patel et al. Intensive Care Med DOI 10.1007/s00134-013-2863-6 2013.
16. Conclusions
• HES recognized as a foreign substance.
• Hydroxyethylation intentionally retards catabolism
– Promotes storage.
• Tissue storage of HES is rapid, widespread, cumulative
and long-lasting.
• Low MW/MS may increase tissue uptake of HES.
• Storage may be fundamental mechanism underlying
recognized complications of HES.