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.
Pharmacodynamic study of Jerusalem artichoke particles in type I and II diabe...Premier Publishers
To study the therapeutic effect of Jerusalem artichoke particles in type I and type II diabetic rats. Male Sprague–Dawley (SD) rats were intraperitoneally injected with 30 mg/kg streptozotocin (STZ) for 3 consecutive days to generate a type I diabetic rat model. The rats were orally administered Jerusalem artichoke particles (50, 100, or 150 mg/kg) once a day for 3 consecutive weeks. Fasting blood glucose levels were determined by ELISA. Male SD rats were fed a high-fat and high-sugar diet then received an intraperitoneal injection of 35 mg/kg STZ to generate a type II diabetic rat model. The rats were treated as mentioned above for 4 consecutive weeks. Fasting blood glucose levels were determined using the glucose oxidase method. Jerusalem artichoke particles significantly reduced blood glucose concentrations in type I and type II diabetic rats. Following 50, 100 and 150 mg/kg Jerusalem artichoke particles treatment for specified weeks, blood glucose concentrations were decreased by 9.7%, 21.69% and 15.48% in type I diabetic rats, respectively; and type II diabetic rats were decreased by 12.07%, 28.57% and 21.80%, respectively. Jerusalem artichoke particles have a hypoglycemic effect in type I and type II diabetic rats.
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
Liver ischemia reperfusion is induced during sur-gical procedures like liver transplantation and re-section. Multiple mechanisms have been postulat-ed to liver damage following liver ischemia reperfu-sion injury, such as oxidative stress and inflamma-tory reactions. The present study declares the pos-sible mechanism of tadalafil, toward modulating the inflammatory response. Forty-eight rats were divided into 4 groups as follows; Sham group sub-jected to midline laparotomy only. Tadalafil group administered Tadalafil 10 mg/kg intraperitoneal 45 min before sham operation. I/R (Ischemia-reperfusion) group, rats undergo 60 min of hepatic ischemia followed by 60 min of reperfusion. Tada-lafil + I/R group rats undergo a similar pattern of I/R after the treatment with Tadalafil 10 mg/kg, 45 min before ischemia. At the end of the reperfusion, the blood samples were collected for estimation of biochemical markers including liver enzymes using colorimetric assay method and serum: TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) le-vels, ICAM- 1 (Intercellular Adhesion Molecule-1) were measured. Tissues were evaluated by semi-quantitative and morphometrical approaches. Ta-dalafil succeeded in restoring normal levels of liverenzymes and ameliorating the oxidative stress as evidenced by decreasing MDA and restoring redu-ced glutathione levels in liver tissue homogenate. Also, Tadalafil exhibits anti-inflammatory effects, as it significantly decreased the levels of TNF-α, IL6 and ICAM-1. The findings are supported by BCL-2, TNF-α immunomarkers. It is concluded that modulation of the inflammatory response might be one of the mechanisms of Tadalafil-mediated he-patoprotection, so it is recommended as an adju-vant therapy in liver surgery.Keywords: Ischemia/reperfusion injury – Oxidative stress – Apoptosis – TNF-α – BCL-2
µCT analysis reveals that Cissus quadrangularis L. Stem and Trigonella foenum...RahulGupta2015
Cissus quadrangularis L. (hadjod) and Trigonella foenum-graecum L. (fenugreek) plant parts are used for fracture healing and as an antidiabetic agent, respectively in traditional medicine. This study aimed to investigate the efficacy of C. quadrangularis stem bark extract (CQ) and T. foenum-graecum seed extract (TFG) therapy for the treatment of type I diabetes induced osteopenia. Alloxan (dissolved in 0.1 M citrate buffer (pH = 4.5); intraperitoneally injected @ 130 mg/kg body weight) induced type I diabetic rats were treated with individual and combined doses of ethanol extracts of CQ and TFG for consecutive 30 days @ 250 and 500 mg per kg body weight, orally. Insulin (0.5 IU/kg body weight) was chosen as standard. Body weight and fasting blood glucose were recorded. Two-dimensional (2D) and three-dimensional (3D) analysis of the femur and tibia were performed using micro-computed tomography (µCT) scan to measure histomorphometric parameters of trabecular and cortical regions and bone mineral density (BMD). Elevated level of fasting blood glucose was restored to the vehicle-treated group after treatment with CQ and TFG. Both the extracts significantly improved trabecular histomorphometric parameters, viz. BMD, percent bone volume, trabecular number, trabecular separation, connection density. Cortical mean total cross-sectional bone area, cross-sectional thickness, mean total cross-sectional tissue area were comparable to the vehicle-treated group. CQ and TFG combination therapy showed a marked improvement in bone microarchitecture and can be given together as a potential alternative medicine to insulin for prevention of type I diabetes induced osteopathy. Therefore, it can be considered in the management of diabetic osteopathy in humans.
Pharmacodynamic study of Jerusalem artichoke particles in type I and II diabe...Premier Publishers
To study the therapeutic effect of Jerusalem artichoke particles in type I and type II diabetic rats. Male Sprague–Dawley (SD) rats were intraperitoneally injected with 30 mg/kg streptozotocin (STZ) for 3 consecutive days to generate a type I diabetic rat model. The rats were orally administered Jerusalem artichoke particles (50, 100, or 150 mg/kg) once a day for 3 consecutive weeks. Fasting blood glucose levels were determined by ELISA. Male SD rats were fed a high-fat and high-sugar diet then received an intraperitoneal injection of 35 mg/kg STZ to generate a type II diabetic rat model. The rats were treated as mentioned above for 4 consecutive weeks. Fasting blood glucose levels were determined using the glucose oxidase method. Jerusalem artichoke particles significantly reduced blood glucose concentrations in type I and type II diabetic rats. Following 50, 100 and 150 mg/kg Jerusalem artichoke particles treatment for specified weeks, blood glucose concentrations were decreased by 9.7%, 21.69% and 15.48% in type I diabetic rats, respectively; and type II diabetic rats were decreased by 12.07%, 28.57% and 21.80%, respectively. Jerusalem artichoke particles have a hypoglycemic effect in type I and type II diabetic rats.
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
Liver ischemia reperfusion is induced during sur-gical procedures like liver transplantation and re-section. Multiple mechanisms have been postulat-ed to liver damage following liver ischemia reperfu-sion injury, such as oxidative stress and inflamma-tory reactions. The present study declares the pos-sible mechanism of tadalafil, toward modulating the inflammatory response. Forty-eight rats were divided into 4 groups as follows; Sham group sub-jected to midline laparotomy only. Tadalafil group administered Tadalafil 10 mg/kg intraperitoneal 45 min before sham operation. I/R (Ischemia-reperfusion) group, rats undergo 60 min of hepatic ischemia followed by 60 min of reperfusion. Tada-lafil + I/R group rats undergo a similar pattern of I/R after the treatment with Tadalafil 10 mg/kg, 45 min before ischemia. At the end of the reperfusion, the blood samples were collected for estimation of biochemical markers including liver enzymes using colorimetric assay method and serum: TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) le-vels, ICAM- 1 (Intercellular Adhesion Molecule-1) were measured. Tissues were evaluated by semi-quantitative and morphometrical approaches. Ta-dalafil succeeded in restoring normal levels of liverenzymes and ameliorating the oxidative stress as evidenced by decreasing MDA and restoring redu-ced glutathione levels in liver tissue homogenate. Also, Tadalafil exhibits anti-inflammatory effects, as it significantly decreased the levels of TNF-α, IL6 and ICAM-1. The findings are supported by BCL-2, TNF-α immunomarkers. It is concluded that modulation of the inflammatory response might be one of the mechanisms of Tadalafil-mediated he-patoprotection, so it is recommended as an adju-vant therapy in liver surgery.Keywords: Ischemia/reperfusion injury – Oxidative stress – Apoptosis – TNF-α – BCL-2
µCT analysis reveals that Cissus quadrangularis L. Stem and Trigonella foenum...RahulGupta2015
Cissus quadrangularis L. (hadjod) and Trigonella foenum-graecum L. (fenugreek) plant parts are used for fracture healing and as an antidiabetic agent, respectively in traditional medicine. This study aimed to investigate the efficacy of C. quadrangularis stem bark extract (CQ) and T. foenum-graecum seed extract (TFG) therapy for the treatment of type I diabetes induced osteopenia. Alloxan (dissolved in 0.1 M citrate buffer (pH = 4.5); intraperitoneally injected @ 130 mg/kg body weight) induced type I diabetic rats were treated with individual and combined doses of ethanol extracts of CQ and TFG for consecutive 30 days @ 250 and 500 mg per kg body weight, orally. Insulin (0.5 IU/kg body weight) was chosen as standard. Body weight and fasting blood glucose were recorded. Two-dimensional (2D) and three-dimensional (3D) analysis of the femur and tibia were performed using micro-computed tomography (µCT) scan to measure histomorphometric parameters of trabecular and cortical regions and bone mineral density (BMD). Elevated level of fasting blood glucose was restored to the vehicle-treated group after treatment with CQ and TFG. Both the extracts significantly improved trabecular histomorphometric parameters, viz. BMD, percent bone volume, trabecular number, trabecular separation, connection density. Cortical mean total cross-sectional bone area, cross-sectional thickness, mean total cross-sectional tissue area were comparable to the vehicle-treated group. CQ and TFG combination therapy showed a marked improvement in bone microarchitecture and can be given together as a potential alternative medicine to insulin for prevention of type I diabetes induced osteopathy. Therefore, it can be considered in the management of diabetic osteopathy in humans.
Dynamics of Combined Oral Contraceptive: A Study of Some Haematological Param...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Transglucosidase improves the gut microbiota profile of type 2 diabetes melli...Enrique Moreno Gonzalez
Recently, the relationship between gut microbiota and obesity has been highlighted. The
present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of
transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients
with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing
the gut microbiota of T2DM patients.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
In recent years as a result of the observation that the toxic effects of boron and its
products have increased intensive studies have been initiated in our country and in the world
regarding its effects, especially in the central nervous system, digestive system and reproductive
system. The aim was to determine the histopathological changes caused by boric acid in rat testis,
liver, kidney and brain tissues by light microscopy after oral administration of toxic dose of acute
boric acid.
Hepatoprotective Activity of Methanolic Extract of Whole Plant of Pulicaria W...IOSRJPBS
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for liver injury. The present study was conducted to evaluate the hepatoprotective activity of methanolic extract of whole plant of Pulicaria wightiana in wistar rats. The studies were conducted using the two popular inducing agents Paracetamol (2 g/kg, p.o.) in 1% NaCMC and Carbon tetrachloride (1 ml/kg). Silymarin (100 mg/kg, p.o.) was used as reference drug in the respective models. The effect was estimated by measuring the enzymatic levels and histo- pathological studies. The methanolic extract of whole plant of Pulicaria wightiana has shown very significant hepatoprotection against both Paracetamol and CCl4 - induced hepatotoxicity study models in wistar rats. This was evidenced by marked reduction in marker enzymes in serum. Histopathological studies also confirmed the hepatoprotective nature of the extract
The Ameliorative Potential of Dexmedetomidine and Benincasa Cerifera Extract ...Prof. Hesham N. Mustafa
Renal ischemia/reperfusion injury (IRI) represents the main reason for acute kidney injury (AKI). Dexmedetomidine (Dex) and Benincasa cerifera (BC) have wide benefits due to their anti-inflammatory and antioxidant properties. This study aims to illustrate the protective effects of BC and Dex on renal IRI in a diabetic model. Sixty adult male albino rats (Wistar strain), weighing 250–300 g, were included in the study. The rats were divided into four groups, as follows: sham group: (non-diabetic); diabetes mellitus (DM) + IRI group: streptozotocin (STZ)-induced diabetic rats exposed to renal IRI on day 30 after diagnosis of diabetes; DM + IRI + BC group: STZ-induced diabetic rats treated with BC (500 mg/kg) for 30 days after diagnosis of diabetes, then exposed to renal IRI; and DM + IRI + Dex group: STZ-induced diabetic rats treated with Dex (100 µg/kg intraperitoneally) 5 min before induction of ischemia on day 30 after diagnosis of diabetes, then exposed to renal IRI. Biochemical parameters, histopathological examination, and immunohistochemical markers were evaluated. A significant improvement in the biochemical, histopathological, and immunohistochemical parameters were observed in the DM + IRI + BC group, while the DM + IRI + Dex group showed improvements in renal IRI and dyslipidemia. The present study demonstrated that oxidative stress plays a chief role in renal IRI in the STZ-induced diabetic model. Treatment with BC achieved excellent ameliorative effects, while treatment with DEX improved renal IRI.
Keywords:
Diabetes; Dexmedetomidine; Ischemia/Reperfusion; Oxidative Stress
Solutions for the developing world will come from the developing worldMary Maier
This presentation looks at the problem of youth unemployment and lack of education, particularly amongst girls, in Africa. This problem will need to be addressed in order for African countries to achieve the Sustainable Development Goals
Dynamics of Combined Oral Contraceptive: A Study of Some Haematological Param...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Transglucosidase improves the gut microbiota profile of type 2 diabetes melli...Enrique Moreno Gonzalez
Recently, the relationship between gut microbiota and obesity has been highlighted. The
present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of
transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients
with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing
the gut microbiota of T2DM patients.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
In recent years as a result of the observation that the toxic effects of boron and its
products have increased intensive studies have been initiated in our country and in the world
regarding its effects, especially in the central nervous system, digestive system and reproductive
system. The aim was to determine the histopathological changes caused by boric acid in rat testis,
liver, kidney and brain tissues by light microscopy after oral administration of toxic dose of acute
boric acid.
Hepatoprotective Activity of Methanolic Extract of Whole Plant of Pulicaria W...IOSRJPBS
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for liver injury. The present study was conducted to evaluate the hepatoprotective activity of methanolic extract of whole plant of Pulicaria wightiana in wistar rats. The studies were conducted using the two popular inducing agents Paracetamol (2 g/kg, p.o.) in 1% NaCMC and Carbon tetrachloride (1 ml/kg). Silymarin (100 mg/kg, p.o.) was used as reference drug in the respective models. The effect was estimated by measuring the enzymatic levels and histo- pathological studies. The methanolic extract of whole plant of Pulicaria wightiana has shown very significant hepatoprotection against both Paracetamol and CCl4 - induced hepatotoxicity study models in wistar rats. This was evidenced by marked reduction in marker enzymes in serum. Histopathological studies also confirmed the hepatoprotective nature of the extract
The Ameliorative Potential of Dexmedetomidine and Benincasa Cerifera Extract ...Prof. Hesham N. Mustafa
Renal ischemia/reperfusion injury (IRI) represents the main reason for acute kidney injury (AKI). Dexmedetomidine (Dex) and Benincasa cerifera (BC) have wide benefits due to their anti-inflammatory and antioxidant properties. This study aims to illustrate the protective effects of BC and Dex on renal IRI in a diabetic model. Sixty adult male albino rats (Wistar strain), weighing 250–300 g, were included in the study. The rats were divided into four groups, as follows: sham group: (non-diabetic); diabetes mellitus (DM) + IRI group: streptozotocin (STZ)-induced diabetic rats exposed to renal IRI on day 30 after diagnosis of diabetes; DM + IRI + BC group: STZ-induced diabetic rats treated with BC (500 mg/kg) for 30 days after diagnosis of diabetes, then exposed to renal IRI; and DM + IRI + Dex group: STZ-induced diabetic rats treated with Dex (100 µg/kg intraperitoneally) 5 min before induction of ischemia on day 30 after diagnosis of diabetes, then exposed to renal IRI. Biochemical parameters, histopathological examination, and immunohistochemical markers were evaluated. A significant improvement in the biochemical, histopathological, and immunohistochemical parameters were observed in the DM + IRI + BC group, while the DM + IRI + Dex group showed improvements in renal IRI and dyslipidemia. The present study demonstrated that oxidative stress plays a chief role in renal IRI in the STZ-induced diabetic model. Treatment with BC achieved excellent ameliorative effects, while treatment with DEX improved renal IRI.
Keywords:
Diabetes; Dexmedetomidine; Ischemia/Reperfusion; Oxidative Stress
Solutions for the developing world will come from the developing worldMary Maier
This presentation looks at the problem of youth unemployment and lack of education, particularly amongst girls, in Africa. This problem will need to be addressed in order for African countries to achieve the Sustainable Development Goals
П. Сутерс "Проявления инсулинорезистентности и гликемический контроль в интен...rnw-aspen
Доклад с 15 Межрегиональной научно-практической конференции "Искусственное питание и инфузионная терапия больных в медицине критических состояний" 21-22 мая 2015 г
Alterations of Mitochondrial Functions and DNA in Diabetic Cardiomyopathy of ...CrimsonPublishersIOD
Alterations of Mitochondrial Functions and DNA in Diabetic Cardiomyopathy of CCK1 Receptors-Deficient Rats by Abdelbary Prince, Magdy A Ghoneim, Abdallah M El-Ebidi, Hala A Mousa and Jin Han in Interventions in Obesity & Diabetes
Objective: Ischemia-reperfusion (I/R) leads to reactive oxygen species formation and cell death in kidney tissue with injury and organ transplantation. Simvastatin (SIM) is an antioxidant, anti-inflammatory, and anticoagulant agent. Alterations in I/R-induced acute kidney injury model with SIM treatment were analyzed.
Study Design: Wistar rats (n=28) were grouped into Sham, Ischemia, I/R, and I/R+SIM treated. Left rat kidney renal vessels were clamped for 60 minutes for ischemia, and the I/R group had 6 hours of reperfusion. 10 mg/kg SIM was given orally for 28 days. MDA, GSH, and MPO were analyzed. Kidney tissues were paraffin embedded, and primary antibodies TNF-α and caspase-3 were applied for immunohistochemistry.
Results: In the I/R group, intense inflammatory cell infiltration around the vessels and necrosis in the glomerular structures were observed. In the treated group, proximal and distal tubular cells were found to be close to normal. Immunoexpression of caspase-3 in the ischemia group was positive in degenerative glomeruli. In the treated group, TNF-α expression was negative in the glomerular structures. MDA and MPO levels were significantly increased in ischemia and I/R.
Conclusion: We suggest that SIM treatment improved kidney tissue structure and function in a model of I/R injury.
Keywords: caspase-3; immunohistochemistry; ischemia/reperfusion; kidney; MPO; simvastatin
The aim of the study was to investigate the damage created in tissue by using an in vivo isolated portal ischemia and reperfusion model in the rat liver and the effects of heparin administration on the complement system. A total of 25 male rats weighing 150-290 gr were used in the study. Following anesthesia with ketamine hydrochloride and xylazine hydrochloride, the incision area was shaved in all rats except the control group. The portal vein was isolated and clamped, and ischemia and reperfusion created. Two groups were sacrificed at the 24th hour and two at the 48th hour. Heparin was administered to one of the groups sacrificed at the 24th hour and not to the other group, and similarly one of the groups sacrificed at the 48th hour received heparin while the other did not. Biochemical and pathologic parameters were used to evaluate the damage using serum and liver tissue samples from the sacrificed rats. We used the liver GSH, MPO and C3 levels and the serum IL-6 level to evaluate the ischemia and reperfusion damage in the liver tissue. Heparin was shown to decrease the damage occurring after ischemia and reperfusion by decreasing complement activation and the MPO and IL-6 levels while increasing GSH levels as a result of the statistical analysis performed. Heparin was shown to prevent tissue damage after ischemia and reperfusion by decreasing complement activation and inflammation.
Bosentan Ameliorates Diabetic Angiopathy and Nephropathy in Streptozotocin-In...iosrjce
Angiopathy and nephropathy are serious problems encountered in management of diabetes mellitus.
Angiotensin II (AII) and endothelins (ETs) receptors play an important role in the pathogenesis of diabetic
complications. The purpose of this study was to investigate the possible renoprotective and antiangiopathic
effects of the non-selective endothelin (ET) receptor blocker bosentan in type 1 diabetic model of albino wister
rats. These rats were divided into four groups ( each group , N= 12 rats): control group (1), control group (2)
treated with bosentan (50 mg/kg/day), untreated diabetic group (3) and diabetic group (4) treated with
bosentan. Induction of type 1 diabetes mellitus in tested rats was performed by a single injection, in the tail vein,
of 35 mg/kg streptozotozin after overnight fast. Treatment with bosentan was continued for 12 weeks during
which the 24h urine volume, urinary albumin content, urine and plasma levels of creatinine as well as mean
non-invasive blood pressure (mean BP) were assessed at the end of each 4 weeks. At the end of the 12
th week
rats were sacrificed then the thoracic aortae were dissected for assessment of the vasorelaxant effect of
acetylcholine. Diabetic rats showed hyperglycemia, polyuria, albuminuria, elevated mean BP, reduced
response to vasorelaxant effect of ACh. Bosentan significantly reduced albuminuria and lowered elevated mean
BP. In addition the drug restored the normal values of creatinine clearance and improved vascular reactivity to
ACh. The present study suggested a possible renoprotective and aortic vasorelaxant effects by bosentan without
a significant effect on the control of blood glucose. The results of the present study was directed towards a
possible role of bosentan, as a drug acting on Endothelin receptors, in the improvement of diabetic angiopathy and nephropathy.
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).
Low beneficial effects of short term antidiabetic diet treatment in streptozo...iosrphr_editor
Oxidative stress is currently suggested to play a role in the pathogenesis of Diabetes mellitus. The role of dietary management in diabetes mellitus is to provide a proper balance of total nutrients while meeting the special dietary needs of the patient. The present study was designated to evaluate the effect of special antidiabetic diet treatment upon oxidative stress parameters in the initial stages of the development of diabetes. Male Wistar strain rats were used as an experimental model, divided into five groups. A significant decrease in superoxide dismutase and total glutathione activities were observed in the liver of diabetic rats when compared with control animals. The plasma level of aminotransferases, creatine kinase, lactate dehydrogenase and urea were significantly increased after induction of diabetes, in all groups under treatment. In contrast, rats fed special diet food, have shown slight different, but not significant changes. The findings of the present study suggest that special diet formula useful for prevention of progressive hyperglycaemia in age induced diabetes in dogs, could not restore the imbalance of cellular defence mechanism provoked by streptozotocin.
Transplantation of Autologous Bone Marrow- Derived Stromal Cells in Type 2 Di...CrimsonpublishersITERM
Type 2 Diabetes is a debilitating metabolic disorder which is also the seventh leading cause of death worldwide. Current therapeutic regimes to date have failed to achieve significant long-term glycemic control even with intensive insulin therapy as revealed by deregulated Hb1Ac and C-peptides levels. In the current study, we have evaluated the effect of regenerative cellular therapy for functional recovery from Diabetic pathophysiology. 10 patients with a median age of 51 years were selected for the study and subjected to bone marrow isolation. These samples were processed under sterile conditions for the enrichment of mononuclear cells (BM MNCs) from bone marrow. After strict quality control and characterization of cells, 2 x 106 cells/kg of BM MNCs were infused back into the patient through the anterior pancreaticoduodenal artery. We performed an evaluation of clinical parameters like Body Mass Index, Fasting Plasma Glucose, Fasting Plasma Insulin, HbA1c and C-peptide levels, and followed up the patients for 12 months. Our study showed a reduction in insulin dependency by ≥ 50%.
Ameliorative potential of the quercetin on lead-induced testicular damage mor...Prof. Hesham N. Mustafa
Background
Quercetin, a naturally occurring flavonoid known for its potent antioxidant properties, has been investigated for its potential in counteracting the harmful effects of lead (Pb) toxicity, which induces apoptosis and oxidative damage in various human tissues. This study aims to assess the reparative effects of quercetin on lead-induced testicular damage.
Methods
Four groups, each comprising ten adult male albino rats, were randomly assigned as follows: Quercetin group, Pb group, Pb + Quercetin group, and control group. All treatments were administered orally via gavage daily for a duration of 30 days. Evaluation of sex hormone levels (serum testosterone, FSH, and LH), cytokines and inflammatory mediators (IL-1β, TNF-α, MCP-1), lead concentration, oxidative and antioxidant stress markers (superoxide anion [O2−], MDA, SOD, CAT, GSH), and sperm characteristics were carried out.
Results
The results demonstrated a significant decline in sex hormones and antioxidants, accompanied by an increase in lead concentrations, cytokines, inflammatory mediators, and oxidative stress indicators (O2−, MDA), while SOD, CAT, and GSH levels were reduced. The Pb-intoxicated group exhibited a substantial increase in dead and abnormal sperm, along with significant reductions in sperm concentration and motility. Morphometrically, a marked decrease was observed in spermatogonia, primary spermatocytes, spermatids, and sertoli cells per seminiferous tubule, as well as epithelial height. Furthermore, coadministration of quercetin exhibited notable benefits. It significantly elevated testosterone levels (P < 0.001), testicular SOD, CAT, and GSH activities, while decreasing MDA levels (P < 0.001). Quercetin also mitigated the deleterious effects of lead toxicity on sperm parameters and restored morphometric variations, including epithelial height.
Conclusions
Quercetin supplementation alongside lead exposure showed a potential for ameliorating degenerative changes caused by lead toxicity in the testicles. This cotreatment effectively reduced oxidative stress, cytokine levels, inflammatory mediators, and restored biochemical alterations, thereby improving morphometric parameters.
The pattern of branching and intercommunications of the musculocutaneous nerv...Prof. Hesham N. Mustafa
Background:
The aim of the present work was to provide evidence about the anatomical variations as regard the origin, distribution, and branching pattern of the musculocutaneous nerve (MCN).
Materials and methods:
Brachial plexus was dissected in 40 upper limbs of 20 male adult cadavers. The pattern of the musculocutaneous nerve was photographed by a digital camera.
Results:
The location and length of the nerve branches between left and right arms were recorded and statistically analyzed. In (90%) of specimens the MCN originates from the lateral cord of the brachial plexus, in (5%) it arose from the median nerve (MN), while in the remaining (5%) specimen, it was absent. The musculocutaneous nerve pierced the coracobrachialis muscle in 90% of specimens, and in the remaining (10%) did not pierce it. The motor branches to biceps brachii muscle were categorized into: Type 1 (90%): one branch that divides to supply the two heads of biceps; Type 2 (5%): double branches, innervating each head of biceps separately. The motor branches to brachialis muscle were categorized into: Type 1 (82.9%): one branch; Type 2 (14.2%): double branches and Type 3 (2.9%): three branches that innervating brachialis muscle. Communications between the MCN and the MN were observed in 35% of specimens.
Conclusions:
The knowledge of the common and uncommon musculocutaneous nerve variations is important especially to the surgeons for carrying out surgical procedures in axilla and arm.
Morphohistometric analysis of the effects of Coriandrum sativum on cortical a...Prof. Hesham N. Mustafa
Objective: Natural compounds can act as metal chelators and oxygen free radical scavengers, which allows them to be used as bioactive antagonists to heavy metals neurotoxicity. The aim of the study to analyze the morphometric effects of Coriandrum sativum (C. sativum) on lead-induced neurotoxicity.
Materials and Methods: Forty Sprague-Dawley albino rats were divided into four equal groups (ten in each group): control group; coriander group: received aqueous C. sativum extracts (600 mg/kg BW for 60 days orally); lead (Pb) group: received a daily dose of lead acetate (Pb) (10 mg/kg BW for 60 days orally); Pb+ coriandrum group: received: aqueous C. sativum extract (600 mg/kg BW) prior to 10 mg/kg BW of Pb. The following parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Layers thickness and nuclei density were analyzed.
Results: Lead levels in blood and tissues were decreased significantly in the Pb group and those findings were corrected significantly (p=0.001) with C. sativum addition. Data exhibited an increase in oxidative stress marker MDA and a decrease in antioxidant enzymes activities (SOD, CAT, and GPx) significantly in the Pb group and those effects were reversed significantly (p=0.001) by C. sativum administration. The cerebellar cortex and all layers of the somatosensory cortex thickness and nuclei density were diminished significantly in the Pb group. The morphometrical measurements were corrected significantly (p=0.001) by C. sativum.
Conclusion: From the findings of the current study, Pb caused noticeable structural and functional variations in the cerebellar cortex and somatosensory cortex. C. sativum corrected these parameters as it possesses chelating and antioxidant potentials.
Background:
The anterolateral ligament (ALL) is a true well-defined ligament in the knee first described in 1879 by Segond. After the work of Claes et al., several studies were conducted about biomechanics and its role in stability of the knee. The anatomical existence of the ALL has been studied by and various radiographic diagnostic modalities and in cadavers. It originates from lateral femoral epicondyle and is inserted between Gerdy’s tubercle and the fibular head. There has been controversy about the existence of ALL in pediatric patients. The aim of this work was to confirm the presence of ALL in pediatric patients by using MRI.
Materials and Methods:
We reviewed the knee MRI scans of 100 pediatric patients (ages between one and 12 yr) who had no knee injury or congenital deformity and had been evaluated by an expert radiologist.
Results:
The ALL was detected in 90% of the pediatric patients with the use of MRI.
Conclusions:
The main finding of this study was that ALL can be seen in pediatric patients using MRI. Despite numerous studies, additional research is needed to further define the role of the ALL in knee function.
Level of Evidence:
Level IV.
Protective effect of garlic extract against maternal and fetal cerebellar dam...Prof. Hesham N. Mustafa
Background: In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy.
Materials and methods: Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination.
Results: The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes.
Conclusions: This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).
Keywords: Purkinje cells; garlic; glial fibrillary acidic protein; lead.
Protective role of co q10 or l carnitine on the integrity of the myocardium i...Prof. Hesham N. Mustafa
Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.
Keywords: Cardiotoxicity; CoQ10 and L-carnitine; Dox; Vimentin; eNOS.
One year mortality rate after hip fracture in the western region of saudi ara...Prof. Hesham N. Mustafa
Background:
The mortality rate of elderly patients who sustain a hip fracture is high compared to the general population. Identifying risk factors can help predict patients at risk of hip fracture to reduce the mortality rate. No studies have shown the mortality rate of patients with hip fractures in the western region of Saudi Arabia. Therefore, this study aimed to identify the risk factors associated with the mortality of patients with hip fractures admitted to the King Abdulaziz Hospital and compare the results with other studies.
Methods:
The mortality rate (within 1 yr or less) in 177 patients over the age of 60 yr who were admitted to the university hospital between July, 2007, and September, 2012, with hip fractures was retrospectively studied. The patients were assessed with regard to gender, age, type of hip fracture, and type of surgical intervention.
Results:
The overall mortality rate 1 yr after hip fracture was 12.43%, and the mean age was 77.77 yr old. The risk factors most associated with mortality were as follows: advanced age (71 to 80 and 81 to 90 yr old), male, peritrochanteric (extracapsular) fracture, and operative fixation with dynamic hip screw.
Conclusions:
The mortality rate of patients with hip fractures within 1 yr has a high-risk potential, especially for male patients over 71 yr of age with peritrochanteric (extracapsular) fractures. Surgical treatment with dynamic hip screw also was shown to be a risk factor between the different treatment options.
Level of Evidence:
Level IV.
Biomarkers of Systemic Lupus Erythematosus and Systemic Sclerosis diseases ac...Prof. Hesham N. Mustafa
Systemic Lupus Erythematosus (SLE) and systemic sclerosis (SSc) are systemic inflammatory autoimmune disorders characterized by a large spectrum of clinical and laboratory features. The aim of the present study was to investigate the possible use of serum level of soluble intercellular adhesion molecule-1(sICAM-1) and soluble interleukin-2 receptor (sIL-2Ra) as biomarkers for monitoring of SLE and SSc disease activity. Moreover, it aimed to compare the specificity and sensitivity as well as cut-off value of both biomarkers in a sample of Egyptian patients. 50 SLE patients, 30 SSc patients and 60 age and sex matched healthy controls were enrolled in our study. sICAM-1and sIL-2Ra were measured in serum samples obtained from all participants. In addition to Erythosedimentation rate (ESR), complete blood count (CBC), Antineuclearantibodies (ANA) estimation, disease activity of both diseases were also assessed. sICAM-1and sIL-2Ra levels were higher in SLE and SSc patients versus control. Both parameters are correlated with each other as well as the activity parameters. A cut-off levels of 455.59 (ng/ml) &2525935 (pg/ml) in both SLE & SSs respectively was observed with the highest specificity and sensitivity. It could be concluded that sICAM-1 and sIL-2Ra are noninvasive biomarkers for SLE and SSc that could play a pathophysiologic role in development and progression of both diseases. Moreover, sICAM-1 and sIL-2Ra are correlated with the disease activity at cut-off values of 455.59 (ng/ml) & 2525935(pg/ml) respectively.
Morphohistometric study of the ligamentum flavum in cervical,thoracic and lum...Prof. Hesham N. Mustafa
ABSTRACT Anatomic characterization and fine structure of the human ligamentum flavum (LF), especially at different spinal levels, represent an attractive focus for the scientific and surgical application. Descrip-tive anatomical and structural study of LF at the cervical, thoracic and lumbar levels of the vertebral column in human cadavers is carried out here. The aim of the work is to clarify the anatomical features and fine structural differences in the human LF at different vertebral levels (cervical, thoracic and lumbar). Specimens of vertebral column were ob-tained from 34 human preserved cadavers. Their average age ranged between 56 and 69 years. Morphometric parameters including height, width and thickness of the ligament flavum at the mid-levels of cervical, thoracic and lumbar regions were measured. Sections obtained from different levels were stained with different stains. Morpho-metric measurements involved the relative elastic area, relative collagen area, elastic area% and collagen area% were measured.The results of the height, width and thickness of the LF at different spinal levels showed gradual increase in their mean values respectively. The LF midline gaps were found in the cervical, thoracic and lumbar regions. The morphometrical measure-ments showed that the average elastic area was highest in the cervical region and lowest in the tho-racic region. In the lumbar region, the percentages of both elastic area and the collagen area were nearly the same. The characterization of morpho-logical and histological aspects of the LF at differ-ent spinal levels will be of great importance for ap-plications in spinal surgery, biomechanical and physical rehabilitation of vertebral column.Keywords: Ligamentum Flavum – Spinal – Collagen and elastic fibers
Correlation between acl injury and involvement of the anterolateral ligament ...Prof. Hesham N. Mustafa
Background:
Clinical testing has demonstrated the role of the anterolateral ligament (ALL) in controlling anterolateral laxity and knee instability at high angles of flexion. Few studies have discussed the association between an anterior cruciate ligament (ACL) injury and ALL injury, specifically after residual internal rotation and a post-ACL reconstruction positive pivot-shift that could be attributed to ALL injury. The goal of this study was to assess the correlation between ALL injury and ALL injury with concomitant ACL injury using MRI.
Material and Methods:
This was a retrospective study of 246 patients with unilateral ACL knee injuries from a database that was reexamined to identify whether ALL injuries occurred in association with ACL injuries. We excluded the postoperative reconstructed cases. The charts were reviewed on the basis of the presence or absence of diagnosed ACL injury with no regard for age or sex.
Results:
Of the 246 patients with ACL injury, there were 165 (67.1%) patients with complete tears, 55 (22.4%) with partial tears, and 26 (10.6%) with sprains. There were 176 (71.5%) patients with ALL and associated ACL injuries, whereas 70 (28.5%) did not have associated ACL injuries. There was a significant statistical relationship between ACL and ALL injuries (P<0.0001).
Conclusions:
There is high incidence of ALL tears associated with ACL injuries. Clinicians should be aware of this injury and consider the possibility of simultaneous ALL and ACL repair to prevent further knee instability.
Level of Evidence:
Level IV.
Neuro-amelioration of cinnamaldehyde in aluminum-induced Alzheimer’s disease ...Prof. Hesham N. Mustafa
Aluminum (Al) is a neurotoxic substance which has played an important role in the etiology, pathogenesis, and development of amyloid-β (Aβ) plaques. This study was carried out to evaluate the neuroprotective effect of aqueous cinnamon extract against aluminum chloride (AlCl3)-induced Alzheimer’s disease. Forty adult male albino rats, randomly divided into four equal groups. Control group; ACE200 group administered aqueous cinnamon extract (ACE) orally; AlCl3 group received daily intraperitoneal (i.p.) injection of AlCl3 for 60 days to induce neurotoxicity and AlCl3 + ACE200 group received a combination of AlCl3 and ACE in the same dose and route as previous groups. Aluminum administration significantly enhanced the memory impairment and the Aβ formation in the rat model. The cerebellum exhibited a significant reduced number of Purkinje cells, marked decrease in the density of dendritic arborization and prominent perineuronal spaces in the molecular layer. There was loss of dendritic spines, neurofibrillary degeneration, and appearance of neuritic plaques. Concomitant administration of AlCl3 and ACE displayed an observable protection against these changes with progressive improvement in memory and intellectual performance. In conclusion, ACE may play a protective role against formation of amyloid-β plaques in cerebellum.
Analytical Study of Clinicopathological Data of Saudi Patients with Osteoarth...Prof. Hesham N. Mustafa
SUMMARY: Knee osteoarthritis (OA) is a common disabling disease. Epidemiological studies have revealed various risk
factors for OA, including sex, aging, obesity, occupational illnesses, and chronic diseases. Here we evaluate the clinical, pathological,
and radiological findings of knee OA in a subset of Saudi patients who were subjected to total knee replacement (TKA). The study
population included 30 Saudi patients with knee OA who were operated by TKA (from June 2014 to December 2015) in the Department
of Orthopedics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia. Patient’s clinical and radiological data were collected
from the hospital files. Pathological examination of the excised superior articular surface of tibia and femoral condyles were done.
Pearson Chi-squared analysis was used to test for differences between the variables in associated risk factors. There were more women
than men. Sixty per cent of patients were older than 60 years [mean age, 59.2 (females) and 61.7 (men) years-old]. All patients exceeded
obesity class 1, with females being more obese than males. Pathological examination of the superior articular surface of tibia and femoral
condyles showed high score lesions, which was more apparent in females than in males. Radiological findings showed that most lesions
were high grade. The findings of this study will help to understand the pathogenesis of OA and improve treatment decision making
relevant to TKA in knee OA in Saudi Arabia and elsewhere.
KEY WORDS: Osteoarthritis; Knee; Arthroplasty.
A Study on the Toxic Effect of Different Doses of Diclofenac Sodium on the De...Prof. Hesham N. Mustafa
SUMMARY: The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by
morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and
divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9
mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth
were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin
and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels,
increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group.
Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects
that are dose-dependent in the prenatal subjected kidney to this drug.
KEY WORDS: Diclofenac sodium; Proximal convoluted tubules; Apoptosis;Cyclooxygenase.
Thymoquinone ameliorates oxidative damage and histopathological changes of de...Prof. Hesham N. Mustafa
ABSTRACT
Lead (Pb) toxicity is known to be a chief environmental health issue, especially for pregnant
women and young children. Today, the use of medicinal herbs in the treatment of many diseases
and different toxic agents has become highly accepted due to their effectiveness and lower costs.
Thymoquinone (TQ), which is extracted from Nigella sativa seeds, is a potent antioxidant and anti
inflammatory agent. This study was designed to explore the optional protectivity of TQ against
maternal and fetal oxidative stress and brain damage induced by Pb administration. Pregnant
rats were distributed into seven groups: control group, TQ group, DMSO group, two groups Pb
treated (160 and 320 ppm), and two groups Pb-treated (160 and 320 ppm) co-treated with TQ.
Administration started from gestation day 1 (GD1) to day 20 (GD20) through oral gavage once
daily. Lead administration caused a dose-dependent toxicity for both mothers and fetuses. Also,
the histopathological assessment of the brains from Pb-treated groups showed marked altera
tions. Co-treatment of with TQ and Pb caused a significant decrease in Pb levels as compared
with those treated with Pb alone and amelioration of histopathological changes in the brains. It
was concluded that co-treatment of TQ along with gestational Pb exposure could mitigate the
effects against Pb-induced maternal and fetal neurotoxicity.
KEYWORDS
Lead; oxidative stress; brain;
Thymoquinone; fetal toxicity
A study on the toxic effect of different doses of Diclofenac sodium on the de...Prof. Hesham N. Mustafa
The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug.
Keywords : Diclofenac sodium; Proximal convoluted tubules; Apoptosis; Cyclooxygenase.
Zingiber Officinale Alleviates Maternal and Fetal Hepatorenal Toxicity Induce...Prof. Hesham N. Mustafa
This study was designed to address the protective effects of Zingiber officinale on the toxic outcomes of prenatal Cadmium administration on pregnancy outcome. Pregnant female Sprague-Dawley rats were randomly divided into four groups (eight rats/each), control group received distilled water, 2nd group treated with 8.8 mg of CdCl2/kg b. wt, 3rd group treated with 250 mg of Zingiber officinale/kg b. wt, and 4th group treated with 250 mg of Zingiber officinale/kg b. wt, followed by 8.8 mg of CdCl2/kg b.wt. Daily body weight of pregnant was recorded from GD1-GD20, and then pregnant rats were sacrificed at GD20. Samples of maternal and fetal livers and kidneys were processed for histological examination. Administration of Cd to pregnant rats showed adverse effects on pregnant mothers and their fetuses; reduced maternal weight gain, reduced absolute organ weights, reduced fetal growth parameters and placental weights together with altered histological appearance of the maternal and fetal livers and kidneys. While co-administration of Zingiber officinale showed an improvement of these toxic alterations. Zingiber officinale through its antioxidant activity could be beneficial against toxic outcomes of Cd exposure during pregnancy.
Evaluation of the safety of conventional lighting replacement by artificial d...Prof. Hesham N. Mustafa
Background
Short morning exposure to high illuminance visible electromagnetic radiations termed as artificial daylight is beneficial for the mental health of people living in geographical areas with important seasonal changes in daylight illuminance. However, the commercial success of high illuminance light sources has raised the question of the safety of long hour exposure.
Methods
We have investigated the effect of the replacement of natural daylight by artificial daylight in Swiss mice raised under natural lighting conditions. Mice were monitored for neurotoxicity and general health changes. They were submitted to a battery of conventional tests for mood, motor and cognitive functions’ assessment on exposure day (ED) 14 and ED20. Following sacrifice on ED21 due to marked signs of neurotoxicity, the expression of markers of inflammation and apoptosis was assessed in the entorhinal cortex and neurons were estimated in the hippocampal formation.
Results
Signs of severe cognitive and motor impairments, mood disorders, and hepatotoxicity were observed in animals exposed to artificial daylight on ED20, unlike on ED14 and unlike groups exposed to natural daylight or conventional lighting. Activated microglia and astrocytes were observed in the entorhinal cortex, as well as dead and dying neurons. Neuronal counts revealed massive neuronal loss in the hippocampal formation.
Conclusions
These results suggest that long hour exposure to high illuminance visible electromagnetic radiations induced severe alterations in brain function and general health in mice partly mediated by damages to the neocortex-entorhinal cortex-hippocampus axis. These findings raise caution over long hour use of high illuminance artificial light.
Beneficial Effects of Curcumin Inmaternal and Fetal Oxidativestress and Brain...Prof. Hesham N. Mustafa
This study was planned to explore the protective role of curcumin (Cur) against maternal and fetal oxidative stress and cerebral damage induced by lead (Pb) during pregnancy. Positively pregnant female rats were divided into seven groups: control group, Cur group (300 mg/kg of Cur/b.wt.), DMSO group (50% DMSO), two Pb-treated groups (exposed to 160 and 320 mg/kg b.wt./day of Pb acetate, respectively), and two groups treated with both Pb and Cur (exposed to Pb as previous groups together with 300 mg/kg b.wt./day of Cur). Treatments through oral gavage once a day started from gestation day 1 (GD1) till day 20 (GD20), where the mother rats of different experimental groups were sacrificed to obtain the fetuses. Different chemical parameters were assessed. Brain specimens of mother and fetal groups were processed with examination. The results displayed that Pb administration to pregnant rats resulted in a dose-dependent toxicity for both mothers and fetuses. Also, there was a significant rise in lipid peroxidation and decreased antioxidant enzyme activities in the brains of the different Pb-treated groups. The histological examination of the brain of treated dams and fetuses showed marked alterations. Co-treatment of Cur along with Pb caused a significant decrease in Pb levels as compared with those treated with Pb alone, improving the oxidative condition with amelioration of the brain’s histopathological changes. Co-administration of Cur could have ameliorative effect against Pb-induced neurotoxicity through the reduction of oxidative stress and reversal of histopathological changes.
Keywords:
Lead; Oxidative Stress; Brain; curcumin; Fetal toxicity
Immunohistochemical Study of the Ameliorative Effect of Vitamin E on Liver Re...Prof. Hesham N. Mustafa
The liver is almost unique in its capacity for regeneration after hepatectomy but the exact mechanisms are not yet fully clarified. Antioxidants have been shown to promote liver regeneration after major hepatectomy. The present study evaluated the ameliorative effect of vitamin E administration on the liver regeneration after different periods of partial hepatectomy (PH) in rats. Fifty-six adult male albino rats were divided into three groups: Control sham operated group; partially hepatectomized group which were divided into three subgroups sacrificed at 1day, 3 days and 7days after the operation respectively; Partially Hepatectomized group with vitamin E pretreatment before PH where the rats were given a daily oral dose of vitamin E until the time of sacrifice of the rats. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and labeling index were demonstrated. After PH, the PCNA positive hepatocytes and the PCNA labeling indices were significantly high after the 1st day and then much decreased after the 3rd day, to be followed by a slight increase at the 7th day. Vitamin E pretreatment in PH rats resulted in a decrease in PCNA positive cells and its labeling indices in the 1st day with a gradual increase in the 3rd and 7th days. Vitamin E has an inhibitory effect in the first 24 hours on liver regeneration followed by stimulatory effect at the third and seventh days after PH. These data indicated that vitamin E pretreatment has an important role in regulation and enhancement of liver regeneration after PH.
Keywords:
Immunohistochemistry; Labeling Index; Vitamin E; Partial Hepatectomy; PCNA
Does allicin combined with vitamin B-complex have superior potentials than al...Prof. Hesham N. Mustafa
BACKGROUND:
The current article aims to explore the protective potentials of α-tocopherol alone and the combination of allicin and vitamin B-complex against lead-acetate neurotoxicity on the cerebellar cortex.
MATERIALS AND METHODS:
Forty rats were divided into four groups (n=10). Group 1 was the control group. Group 2 received 10 mg/kg body weight (BW) of lead acetate. Group 3 was exposed to 10 mg/kg BW of lead acetate plus a combination of allicin (100 mg/kg BW) and vit. B-complex (40 mg/kg BW). Group 4 was administered lead acetate (10 mg/kg BW) and α-tocopherol (100 mg/kg BW). The animals received treatment for sixty days by oral gavage. All the groups were studied ultrastructurally and immunohistochemically with glial fibrillary acidic protein (GFAP).
RESULTS:
The affected groups revealed shrunken and degenerated Purkinje cells with irregular nuclei. The cytoplasm comprised several lysosomes, unhealthy mitochondria, and dilated Golgi saccules. The myelinated nerve fibers demonstrated breaking of the myelin sheaths, apparent vacuoles, and broad axonal spaces. Immunohistochemically, there was a tremendous surge in GFAP-positive astrocytes in the lead acetate-treated group. These histological and ultrastructural variations were ameliorated by the administration of α-tocopherol and the combination of allicin and vit. B complex. Moreover, an apparent decrease in the number of GFAP-positive astrocytes was obvious in the protected groups.
CONCLUSIONS:
Although both α-tocopherol and the combination of allicin and vit. B-complex can be used as possible adjuvant therapies to ameliorate nervous system ailments attributable to lead acetate, α-tocopherol showed more protective potential.
KEYWORDS:
Allicin; Astrocytes; GFAP; Myelin Figure; Oligodendrocyte; Purkinje cells
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
3. 82 H.N. Mustafa / Tissue and Cell 48 (2016) 81–88
2. Materials and methods
2.1. Ethical approval
This study was conducted after receiving the approval of the
Medical Research Ethics Committee, Faculty of Medicine, King
Abdulaziz University, Jeddah, Saudi Arabia.
2.2. Chemicals and Reagents
Streptozotocin (STZ) and curcumin were purchased from
Sigma–Aldrich Chemicals (St. Louis, MO, USA). Alanine amino-
transferase (ALT), aspartate aminotransferase (AST), and alkaline
phosphatase (ALP) kits were purchased from Randox Laboratories
Ltd. (Crumlin, County Antrim, UK). Serum albumin, total protein,
and total bilirubin colorimetric kits were supplied by the Bio Diag-
nostic Company (Cairo, Egypt).
2.3. Animals
Sixty male adult albino Wistar rats, weighing 190 ± 20 g, that
were used were obtained from the animal house. Animals were
housed in a (24 ◦C ± 3 ◦C) temperature-controlled room with
40–70% humidity and 12/12 h light/dark cycle. Rats were fed a
standard diet and tap water ad libitum throughout the experiment.
The experimental procedures were performed in accordance with
the international guidelines for the care and the use of animals in
a laboratory.
2.4. Induction of diabetes
Fasted rats (12 h) received a single intraperitoneal (IP) injection
of freshly prepared STZ (50 mg/kg body weight) dissolved in 0.1 M
citrate buffer (pH 4.5). STZ-injected animals were given a 5% glu-
cose solution for 24 h to overcome drug-induced hypoglycemia. On
the third day after STZ injection, glucose levels were estimated by
obtaining blood samples from the cut tip of the tail using Diagnos-
tic Accu-Chek test strips (Roche Diagnostics, Mannheim, Germany).
Blood glucose levels of 250 mg/dl or more were considered diabetic.
2.5. Experimental design
The animals were distributed into 3 groups (20/group). Group
1 (normal control) was injected IP with a citrate buffer vehicle.
Group 2 (diabetic control) received a single IP injection of STZ
(50 mg/kg body weight). Group 3 received a single IP injection of
STZ (50 mg/kg body weight) and, on the third day after the STZ
injection, curcumin was given orally with a dosage of 80 mg/kg
body weight and continued daily for 60 days (Zhang et al., 2013). At
the end of the experiment, blood samples were collected from the
retro-orbital sinus in heparinized capillary tubes for serum anal-
ysis. Animals from all groups were sacrificed, and the livers were
processed for histological studies.
2.6. Plasma glucose estimation
Plasma glucose was measured using an enzymatic colorimet-
ric method with commercially available kits (Randox Laboratories,
Ltd., Antrim, UK).
2.7. Plasma insulin estimation
Plasma insulin was determined using an insulin enzyme-linked
immunosorbent assay (ELISA) kit (code no. AKRIN-010T; Shibayagi
Co., Ltd., Gunma, Japan).
2.8. Serum parameters
ALT, AST, and ALP, which were increased following hepatocyte
injury, were assessed according to the protocol detailed in the
manuals of the diagnostic kits (Randox Laboratories Ltd., Crum-
lin, County Antrim, UK). Serum albumin, total protein, and total
bilirubin were determined by spectrophotometer using the cor-
responding colorimetric kits supplied by Bio Diagnostic Company
(Cairo, Egypt) (Lee et al., 2012).
2.9. Histological examination
Livers were washed with a phosphate buffer solution and then
fixed in 10% neutral buffered formalin. Tissues were dehydrated
through a graded series of alcohol, cleared in xylene, and embed-
ded in paraffin wax. Tissues were then cut into sections of 3–5 m
in thickness using a microtome and stained with hematoxylin and
eosin (H&E) for histopathological evaluation and with periodic
Acid-Schiff (PAS) for observation of glycogen. For each specimen,
at least three to five slides were examined using an Olympus
BX53 microscope equipped with a DP73 camera (Olympus, Tokyo,
Japan).
2.10. Histopathological evaluation
The sections were analyzed for hydropic swelling, parenchy-
matous degeneration, microvesicular vacuole, macrovesicular
vacuole, focal necrosis, inflammatory infiltrations, fibrosis, and
sinusoids hyperemia. At the end of the analyses, the findings were
presented in a table which showed the degree of degeneration
(Guven et al., 2006). Score levels of 0, +1, +2, +3 were equiva-
lent to no, mild, moderate, and severe, respectively. The scores
represented values obtained from the tissue sections of six ani-
mals from each group with five fields/section (Mustafa et al.,
2015).
2.11. Immunohistochemical examination
The standard peroxidase immunohistochemistry technique was
applied to slides of paraffin-embedded tissue. Sections were
de-waxed in xylene, rehydrated, and pretreated with 3% of hydro-
gen peroxide solution to block endogenous peroxidase activity.
Microwave-assisted antigen retrieval was performed for 20 min.
Slides were then incubated overnight at 4 ◦C with the primary
antibody against ␣-SMA (a mouse monoclonal antibody [Dako,
Carpinteria, California, USA] with a dilution of 1:50; cellular site was
cytoplasmic) as a marker of activated HSCs with varying degrees
of intensity in smooth muscles and myofibroblasts. They were
similarly incubated with the primary antibody against insulin (a
mouse monoclonal antibody [Dako, Carpinteria, California, USA]
with a dilution of 1:100; cellular site was cytoplasmic). The sections
were incubated with biotinylated IgG and then with streptavidin-
peroxidase conjugate (Zymed Corp, San Francisco, CA, USA).
Sections were then washed with phosphate-buffered saline (PBS)
and incubated with 3, 3 -diaminobenzidine tetrachloride (DAB)
substrate chromogen solution (1 drop of DAB chromogen/1 mL of
substrate buffer) for 5 min to detect immunoreactivity. All sections
were counter-stained with Mayer’s hematoxylin. Negative control
sections were prepared by omitting the primary antibody. Positive
control standard laboratory slides were used for all stains to prove
the success of the technique. All slides were examined under light
microscopy, and the presence of labeled cells was documented.
Absence of staining was recognized as a negative result (−), while
the presence of brown staining was recognized as positive result
(+) (Mustafa et al., 2015).
4. H.N. Mustafa / Tissue and Cell 48 (2016) 81–88 83
Table 1
Body and liver weight of different groups.
Normal control (n = 20) STZ-diabetic control (n = 20) STZ-diabetes + curcumin (n = 20)
Liver weight (g) 11.14 ± 1.54 9.91 ± 1.04
P* < 0.01
10.83 ± 0.85
*P > 0.05
**P < 0.05
Body weight (g) 187.65 ± 6.11 163.94 ± 4.9
*P < 0.001
180.47 ± 3.89
*P < 0.001
**P < 0.001
Values are means ± SD (n = 20 each group). ANOVA followed by Tukey’s post hoc test.
*P: compared to normal control. **P: compared to diabetic control.
Fig. 1. Body and liver weight of different groups. The mean is given in columns, and error bars represent the standard deviation (SD).
2.12. Quantitative morphometric measurements
Ten non-overlapping fields for each animal were selected indis-
criminately and analyzed. The measurements were done by using
Image-Pro Plus v6.0 software (Media Cybernetics, Silver Spring,
MD, USA) and the NIH ImageJ (v1.50) program (http://rsb.info.
nih.gov/ij/) with an Olympus BX53 microscope (Olympus, Tokyo,
Japan). The area percentages of ␣-SMA immunopositive cells and
the insulin-positive cells number were evaluated (Hussein et al.,
2015).
2.13. Statistical analysis
Quantitative data were expressed as the mean ± SD of different
parameters for the treated groups. The data were analyzed using
one-way analysis of variance (ANOVA) followed by Tukey’s post hoc
test. The statistical analysis was performed using IBM SPSS version
23. The values were considered significant when p < 0.05.
3. Results
3.1. Effect on liver and body weight
At the end of 60 days, curcumin treated specimens showed a
significant increase in the body and liver weight as compared to
the diabetic control (Table 1 and Fig. 1).
3.2. Biochemical parameters
The mean glucose level of the diabetic control group was signif-
icantly increased while curcumin treatment showed a significant
improvement in glucose level (Table 2 and Fig. 2). The mean insulin
level of the diabetic control group was significantly decreased while
curcumin treatment showed a significant improvement in insulin
level (Table 2 and Fig. 2).
Plasma ALT, AST, and ALP levels were elevated in the diabetic
control group in comparison to those of the normal control group,
while with curcumin treatment all of these parameters are reduced
significantly. Furthermore, there was a significant decrease in the
albumin and total protein in the diabetic control group, while
curcumin treatment showed a significant increase in these param-
eters compared to those of the diabetic control group. Conversely,
the total bilirubin was increased in the diabetic control group
and decreased significantly with curcumin treatment (Table 2 and
Fig. 3).
3.3. Histopathological findings
The normal control group showed normal cytoarchitecture. The
diabetic control group showed parenchymatous degeneration and
loss of architecture. With curcumin treatment, hepatic changes
were reduced (Table 3).
PAS-stained sections of the normal control group showed PAS-
positive red granules in the cytoplasm of the hepatocytes and
more granules around the central vein (Fig. 4A), while those
of the diabetic control group showed few PAS-positive granules
(Fig. 4B). With curcumin treatment, mild PAS-positive granules
were observed (Fig. 4C and Table 3).
3.4. Immunohistochemistry-stained sections
In the normal control group, ␣-SMA staining was observed only
in the media of the blood vessels (portal veins, hepatic artery
branches, and central veins) (Fig. 5A). While the diabetic control
group showed positive ␣-SMA immunoreactivity in the media of
the portal vessels and the periportal area and along the perisinu-
soidal spaces (Fig. 5B and C). In the curcumin treatment group,
mild immunoreactivity was observed (Fig. 5D). The area percent-
age of ␣-SMA positive cells was significantly higher in the diabetic
control group, while in the curcumin treatment group it was
reduced significantly (Table 4 and Fig. 7).
Insulin-immunostained sections for both the normal control
(Fig. 6A) and diabetic control (Fig. 6B) groups showed no or mini-
mal insulin immune positive cells. The curcumin treatment group
showed many insulin positive immune cells in the portal area
around the bile ductule (Fig. 6C). The number of insulin positive
cells was significantly higher in the curcumin treated group (Table 4
and Fig. 7).
5. 84 H.N. Mustafa / Tissue and Cell 48 (2016) 81–88
Fig. 2. Plasma glucose and insulin of different groups. The mean is given in columns, and error bars represent the standard deviation (SD).
Table 2
Biochemical parameters of the different groups.
Parameters Normal control STZ-diabetic control STZ-diabetes + curcumin
Plasma glucose (mg/dl) 87.14 ± 4.28 280.12 ± 57.24
*P < 0.001
160.12 ± 63.27
*P < 0.001
**P < 0.001
Plasma insulin (mIU/L) 5.17 ± 0.73 0.54 ± 0.11
*P < 0.001
4.06 ± 0.45
*P < 0.001
**P < 0.001
ALT (U/l) 65.4 ± 1.2 119.6 ± 2.30
*P < 0.001
76.8 ± 4.60
*P < 0.001
**P < 0.001
AST (U/l) 139.13 ± 3.82 321.35 ± 2.80
*P < 0.001
204.68 ± 1.96
*P < 0.001
**P < 0.001
ALP (U/l) 68.10 ± 2.30 85.2 ± 4.60
*P < 0.001
79.5 ± 8.10
*P < 0.001
**P < 0.01
Albumin (g/dl) 4.14 ± 0.60 1.3 ± 0.87
*P < 0.001
3.81 ± 0.40
*P > 0.05
**P < 0.001
Total protein (g/dL) 5.94 ± 0.89 2.03 ± 0.78
*P < 0.001
4.62 ± 0.13
*P < 0.001
**P < 0.001
Total bilirubin (mg/dL) 0.24 ± 0.20 0.78 ± 0.07
*P < 0.001
0.36 ± 0.06
*P < 0.05
*P < 0.001
Values are means ± SD (n = 20 each group). ANOVA followed by Tukey’s post hoc test.
*P: compared to normal control. **P: compared to diabetic control.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; mg/dl, milligrams per deciliter; mIU/L, milli-international units per liter; U/l,
units per liter; g/dl, grams per deciliter.
4. Discussion
In the current study, the diabetic control group revealed a reduc-
tion in body weight, which is attributed to the muscle destruction or
catabolism of structural protein and fat (Salahuddin and Jalalpure,
2010). Curcumin administration improves the body weight, and
this indicates the effect of curcumin on the degradation of struc-
tural protein, control of muscle wasting, and increase of metabolic
processes in the body.
The current data showed a significant decrease in the plasma
insulin levels, which coincides with other findings (Abdel Aziz et al.,
2013). Improved insulin level supports the hypothesis that cur-
cumin causes -cells neogenesis and protection (Meghana et al.,
2007), and this was evidently proven by this study. Furthermore,
it is proposed that controlling hyperglycemia encourages further
regeneration of -cells (Guz et al., 2001). This may be attributed
to the suggestion that dying -cells are regenerated continuously
(Montanya et al., 2000).
Hepatocellular injury is credited to reactive oxygen species
(ROS) and lipid peroxidation that causes direct damage to hepa-
tocytes by disrupting the membranes, protein, and DNA (Asmah
Rahmat, 2015). The injured hepatocytes release aldehyde end prod-
ucts, which causes further hepatocellular damage and emergence of
fibrosis (Novo and Parola, 2012). Also, lipid peroxidation causes an
inflammatory reaction that involves the occurrence of cytokines,
mainly tumor necrosis factor (TNF-␣), interleukin-1 (IL-1), and
consensus interferon (IFN-c) (Sugano et al., 2006). Meanwhile, cur-
cumin treatment alleviates the hepatocellular injuries.
In the present study, the diabetic control group revealed a con-
gestion of the portal triad with inflammation and notable fibrosis
near the central vein. This is attributed to tissue degradations that
are caused by depletion of the endogenous antioxidant enzyme
stores as superoxide dismutase (SOD) and catalase (CAT) (Chang
and Chuang, 2010) and promotion of de novo generation of free
radicals (Maritim et al., 2003). Consequently, the higher level of
antioxidants that exists in curcumin could boost the quenching of
some free radicals inside hepatocytes, which defend the hepatic
tissue against oxidative stress damage (Afrin et al., 2015), and this
is supported by the current findings.
In liver impairment, hepatic stellate cells (Ito cells)
undergo trans-differentiation from lipid storing pericytes to
myofibroblast-like cells that lead to an increased collagen and
extracellular matrix that is the crucial event in hepatic fibrogenesis
(She et al., 2005). Curcumin treatment in the current study caused
a reduction of ␣-SMA positive cells, which is the marker of Ito
cell activation and in turn, indicates inhibition of Ito cells and the
improvement of hepatic fibrosis (Erenoglu et al., 2011).
Curcumin suppresses the AGEs mediated by the stimula-
tion of RAGEs gene expression. This leads to inhibition of the
RAGE activated pathways which, in turn, prevents oxidative
6. H.N. Mustafa / Tissue and Cell 48 (2016) 81–88 85
Fig. 3. Biochemical parameters of different groups. The mean is given in columns, and error bars represent the standard deviation (SD).
Table 3
Histopathological findings of the liver.
Normal
control
STZ-diabetic
control
STZ-
diabetes +
curcumin
Hydropic swelling 0 +2 +1
Parenchymatous degeneration 0 +2 +1
Microvesicular vacuole 0 +0.5 +1
Macrovesicular vacuole 0 +0.5 +1
Focal necrosis 0 +2 +0.5
Inflammatory infiltrations 0 +1 +1
Fibrosis 0 +1 +0.5
Sinusoids hyperemia 0 +2 +1
PAS +3 +1 +2
N = 20; Scale: No (0), mild (+1), moderate (+2), severe (+3).
stress, inflammation, and hepatic stellate cell activation, a hall-
mark of non-alcoholic steatohepatitis and hepatic fibrogenesis
associated with type 2 diabetes mellitus (Stefanska, 2012). More-
over, AGE-encouraged production of reactive oxygen species and
lipid peroxides was attenuated after treatment with curcumin
(Stefanska, 2012).
In the current findings, the trans-differentiation of Ito cells into
myofibroblast-like cells is attributed to intercellular connections
between Ito cells and activated Kupffer cells, damaged hepatocytes,
and inflammatory cytokines (Hellerbrand, 2013). Other factors that
cause this trans-differentiation include the platelet-derived growth
factor (PDGF), epidermal growth factor (EGF), and transforming
growth factor 1 (TGF-1) that are released after activation of
Kupffer cells (Nosseir et al., 2012).
In hyperglycemic conditions, the diabetic control group in the
current study showed minimal insulin immune reactions of hepatic
stellate cells. This indicates that diabetes encourages the transi-
tion of hepatic stellate cells to insulin-producing cells but it cannot
maintain their production. Furthermore, it was found that this
trans-differentiation occurs early and lasts for two weeks in the
diabetic liver (Kim et al., 2007). This transition is attributed to the
fact that both the liver and the pancreas originate from the upper
primitive foregut endoderm appendages (Lammert et al., 2003) and
the late separation of the pancreas and liver during organogenesis
might leave pluripotent cells, which are able to give rise to both
pancreatic and hepatic lineage (Meivar-Levy and Ferber, 2003).
In supporting this hypothesis, a previous study has discussed the
existence of extra-pancreatic insulin-producing cells in the liver in
the hyperglycemic condition. However, the number and produc-
tion of these insulin-producing cells are not enough to improve the
hyperglycemic condition (Kojima et al., 2004). The current results
support the hypothesis that the hypoglycemic effect of curcumin is
attributed to preserving functional insulin-producing cells. In the
curcumin group in the current study, insulin immune positive cells
were increased which supports the suggestion that curcumin may
maintain insulin production by trans-differentiated hepatic stellate
cells for a period after STZ injection.
These results optimistically demonstrate the potential use
of curcumin for the treatment of STZ-induced liver damage
because of its antiradical/antioxidant activities, potential -cell
regenerative properties, and 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
7. 86 H.N. Mustafa / Tissue and Cell 48 (2016) 81–88
Fig. 4. (A) Normal control group showed PAS-positive reaction (distribution of liver glycogen) (arrow); (B) diabetic control group showed few PAS-positive reaction (arrow);
(C) curcumin treatment group showed mild PAS-positive reaction (arrow) (PAS, scale bar 20 m).
Fig. 5. (A) Normal control group showed minimal immunostaining (arrow); (B) diabetic control group showed positive immunostaining (activated HSCs) in the media of the
portal blood vessels and scattered in the periportal area (arrow); (C) the previous group with positive immunostained cells in the perisinusoidal spaces (arrow); (D) curcumin
treatment group showed mild immunostaining (arrow) (␣-SMA, scale bar 20 m).
8. H.N. Mustafa / Tissue and Cell 48 (2016) 81–88 87
Table 4
Mean ± SD of the area percentage of ␣-smooth muscle actin positive cells and the number of insulin-positive cells.
Normal control STZ-diabetic control STZ-diabetes + curcumin
Area % of ␣-SMA 0.43 ± 0.28 10.20 ± 0.62
*P < 0.001
1.06 ± 0.87
*P < 0.01
**P < 0.001
Number of insulin positive cells 0.00 0.28 ± 0.01
*P > 0.05
5.10 ± 3.50
*P < 0.001
**P < 0.001
Values are means ± SD (n = 20 each group). ANOVA followed by Tukey’s post hoc test.
*P: compared to normal control. **P: compared to diabetic control.
Fig. 6. (A) Normal control group showed a negative immune reaction; (B) diabetic control group showed a minimal immune reaction; (C) the curcumin treatment group
showed strong positive immunoreactivity (insulin-producing cells) (arrows) (insulin immune reaction, scale bar 20 m).
Fig. 7. Area % of ␣-SMA and number of insulin positive cells. The mean is given in columns, and error bars represent the standard deviation (SD).
myofibroblast-like cells, consequently the way is now open to
consider curcumin’s novel therapeutic effects in reducing hepatic
dysfunction in diabetic patients.
5. Conclusion
The current data suggest that curcumin affects hepatic stel-
late cell activation, which represents a key event of non-alcoholic
steatohepatitis and hepatic fibrogenesis associated with diabetes.
Conflicts of interest
None.
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