γδ T-cell lymphoma: a rare entity mimicking hemophagocytic syndrome-report of two cases

γδ T-cell lymphoma is a rare extranodal and systemic neoplasm which accounts for less than 1% of all NHL having peak incidence in adolescents and young adults with a male predominance. Study report two cases, 29 and 25 years male presented with fever, abdominal pain and pancytopenia; one had hepatosplenomegaly while other had marked splenomegaly respectively and both showing feature of hemophagocytosis. Both underwent splenectomy. On gross examination, the spleen was markedly enlarged and shows a deep brown cut-surface. Histologically the normal structure of the spleen is totally effaced by a monotonous lymphoid population consisting of medium-large sized lymphoid cells with vesicular chromatin and small eosinophilic nucleolus with tumor cells showing moderate amount of eosinophilic cytoplasm. Liver biopsy showed regenerative changes in parenchyma and sinusoidal involvement by tumour cells. Peripheral smear revealed atypical lymphocytes with pancytopenia. Bone marrow aspiration showed moderate neoplastic infiltrate by lymphoid cells. Immunophenotypic study showed tumour cells expressing CD3, CD56, CD 2 (dim), TIA-1, TCR-gamma. The tumour cells were immunonegative for CD20, CD5, CD4, CD8, granzyme B, CD7, CD10 and CD 23. Immunophenotypic study is must for diagnosis of   γδ T-cell lymphoma which can mimic hemophagocytic syndrome

Mitigating effects of vildagliptin in experimental diabetes with metabolic syndrome

Background: Vildagliptin has multiple beneficial effects reported in isolated studies like anti-diabetic, cardio protective, anti-inflammatory and antioxidant. However, there is no experimental evidence presently available with regard to the possible beneficial effects of vildagliptin on attenuating changes observed in metabolic syndrome co-existing with diabetes in experimental rats. Thus, the present study was designed to evaluate potential effects of vildagliptin on various components of metabolic syndrome. Also to elucidate the underlying mechanisms: DPP-IV, anti-inflammatory, antioxidant pathways were studied.Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in wistar rats. The HFD were fed to rats for 10 weeks to induce metabolic syndrome. At the end of 3 weeks, diabetes was induced by a single STZ injection (40 mg/kg body weight). Vildagliptin (10 mg/kg) was administered to rat from 5th to 10th weeks daily and various parameters of Diabetes and metabolic syndrome were studied. Also to understand the mechanisms; DPP-IV pathway, anti-inflammatory, antioxidant parameters were studied. Biochemical indices of injury (pancreatic, liver and renal function) and histopathological assessment of injury was evaluated in experimental groups. Immunohistochemistry of pancreas was done to assess beta cell mass.Results: The vildagliptin treatment ameliorated the deleterious effects associated with metabolic syndrome and diabetes. The beneficial effects demonstrated by vildagliptin on various parameters include: anti-diabetic (reduced blood glucose, HbA1c, HOMA-IR, increased serum insulin, HOMA-β and restoration of pancreatic function), central obesity (reduced body weight, abdominal circumference (AC), thoracic circumference (TC), AC/TC ratio) and hypolipidemic (favourable lipid profile, artherogenic index) activity. A significant restoration of cardiac injury as indicated by CPK-MB levels was observed. In addition, DPP-IV pathway (reduced serum DPP-IV), anti-inflammatory (reduced hs-CRP levels), and antioxidant (reduced MDA) contributed its beneficial effects in diabetes with metabolic syndrome model. The protective effects on heart, pancreas, liver and kidney were confirmed by histopathological report. The immunohistochemical report of pancreas showed preservation of beta cell mass in vildagliptin treated rats.Conclusions: Vildagliptin treatment ameliorates deleterious changes of diabetes with metabolic syndrome. Beneficial effects of vildagliptin can be attributed to hypoglycemic, hypolipidemic, antioxidant, cardioprotective and anti-inflammatory effects

Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia (increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol), diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component

DPP-4 inhibitory activity and myocardial salvaging effects of Commiphora mukul in experimental diabetes

Background: Commiphora mukul (Burseraceae) is commonly known as Guggul in Ayurveda. Several studies have reported antidiabetic activity of Commiphora mukul but there are no studies to explore the DPP-4 inhibitory activity and myocardial salvaging effects of Commiphora mukul in setting of diabetes mellitus. The present study was designed to evaluate the cardioprotective efficacy as well as safety of the medicinal plant Commiphora mukul (Guggul) in the experimental model of myocardial infarction co-existing with diabetes.Methods: Diabetes was induced with single dose of streptozotocin (STZ): 45mg/kg ip and myocardial infarction was produced by administering isoproterenol (ISP): (85mg/kg, sc) to rats 24 and 48 h prior to scarification (5th week). After the confirmation of diabetes on 7th day (glucose>200mg/dl), vildagliptin (10 mg/kg) and Commiphora mukul (200 mg/kg) were administered orally from 1st to 5th week (4 weeks). At the end of experimental period, normal control, diabetic-isoproterenol control, vildagliptin and Commiphora mukul group rats were sacrificed for further biochemical investigations as well as histopathological evaluation.Results: Commiphora mukul treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB serum DPP-4, hs-CRP levels as compared to diabetic ISP control group. In addition, Commiphora mukul showed significant cardioprotection as indicated by positive correlation between cardiac marker CPK-MB and serum DPP-4. The histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Commiphora mukul. In addition, Commiphora mukul was found to be safe to the liver and kidney.Conclusions: The natural DPP-4 inhibitor Commiphora mukul demonstrated significant cardioprotective effects in experimental model of myocardial infarction co-existing with diabetes

Myocardial salvaging effects and mechanisms of metformin in experimental diabetes

Background: Several epidemiological studies have found that in type II diabetic patients, Metformin improves vascular function and reduces cardiovascular events and mortality by mechanisms that are not entirely attributed to its anti- hyperglycemic effects; So far the effect of Metformin on experimentally induced myocardial infarction in setting of type II diabetic rats has not been studied. The aim of the present study was to investigate potential cardioprotective effects and mechanisms of Metformin subsequent to isoproterenol induced myocardial infarction in the setting of diabetes.Methods: Diabetes was induced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was produced by administering isoproterenol (ISP): (85mg/kg, sc) to rats 24 and 48 h prior to sacrification (5th week). After the confirmation of diabetes on 7th day (Glucose>200mg/dl), Metformin (100 mg/kg) was administered and various parameters like anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB, hs-CRP), metabolic (lipid profile, artherogenic potential), antioxidant (MDA) safety {pancreatic function (lipase), liver function (SGPT), kidney function (Creatinine) and histopathological indices of injury were evaluated in experimental groups.Results: Administration of STZ-ISP resulted in a significant decrease in body weight (p<0.001), diabetic changes (increase in blood glucose, HbA1c), cardiac injury (leakage of myocardial CPK-MB), altered lipid profile, anti-inflammatory, antioxidant, lipase, SGPT, creatinine levels (p<0.01) in the Diabetic- ISP Control group rats as compared to Normal Control. Metformin (100 mg/kg) treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels (p<0.001) compared to Diabetic- ISP Control group. In addition, Metformin favorably modulated the lipid parameters (total cholesterol, triglycerides, HDL, LDL), artherogenic index; antioxidant (MDA) potential, Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Metformin (100 mg/kg) in setting of diabetes.Conclusions: The present study concluded that Metformin at 100 mg/kg demonstrated myocardial salvaging effects in type II diabetic rats challenged with experimental Myocardial infarction. The antioxidant, hypoglycemic, hypolipidemic and anti-inflammatory effects of Metformin may contribute to its beneficial effects.

Myocardial salvaging effects and mechanisms of metformin in experimental diabetes

Background: Several epidemiological studies have found that in type II diabetic patients, Metformin improves vascular function and reduces cardiovascular events and mortality by mechanisms that are not entirely attributed to its anti- hyperglycemic effects; So far the effect of Metformin on experimentally induced myocardial infarction in setting of type II diabetic rats has not been studied. The aim of the present study was to investigate potential cardioprotective effects and mechanisms of Metformin subsequent to isoproterenol induced myocardial infarction in the setting of diabetes.Methods: Diabetes was induced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was produced by administering isoproterenol (ISP): (85mg/kg, sc) to rats 24 and 48 h prior to sacrification (5th week). After the confirmation of diabetes on 7th day (Glucose&gt;200mg/dl), Metformin (100 mg/kg) was administered and various parameters like anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB, hs-CRP), metabolic (lipid profile, artherogenic potential), antioxidant (MDA) safety {pancreatic function (lipase), liver function (SGPT), kidney function (Creatinine) and histopathological indices of injury were evaluated in experimental groups.Results: Administration of STZ-ISP resulted in a significant decrease in body weight (p&lt;0.001), diabetic changes (increase in blood glucose, HbA1c), cardiac injury (leakage of myocardial CPK-MB), altered lipid profile, anti-inflammatory, antioxidant, lipase, SGPT, creatinine levels (p&lt;0.01) in the Diabetic- ISP Control group rats as compared to Normal Control. Metformin (100 mg/kg) treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels (p&lt;0.001) compared to Diabetic- ISP Control group. In addition, Metformin favorably modulated the lipid parameters (total cholesterol, triglycerides, HDL, LDL), artherogenic index; antioxidant (MDA) potential, Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Metformin (100 mg/kg) in setting of diabetes.Conclusions: The present study concluded that Metformin at 100 mg/kg demonstrated myocardial salvaging effects in type II diabetic rats challenged with experimental Myocardial infarction. The antioxidant, hypoglycemic, hypolipidemic and anti-inflammatory effects of Metformin may contribute to its beneficial effects.