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Biomedical subjects

A K Dinda

Publications and source records attributed to A K Dinda.

At least 19 recordsLinked to original sources

Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India.

The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus has only recently been available in India. We report an initial experience using tacrolimus as de novo therapy in a living related renal transplant program. Fifty-two consecutive recipients of living renal allografts were treated with tacrolimus, mycophenolate mofetil, or azathioprine and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12 ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The effect of this regimen on the lipid profile as well as the incidence of posttransplant diabetes mellitus was evaluated in an Indian population. All patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks). The incidence of acute rejection was 3.84%; 17.3% developed posttransplant diabetes mellitus. Graft and patient survivals at the current follow-up were 100% and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant in a living related renal transplant program.

Adolescent↗

Significance of protocol biopsies in living related renal transplant recipients.

INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. RESULTS: SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Adolescent↗

Extract from Clerodendron colebrookianum Walp protects rat heart against oxidative stress induced by ischemic-reperfusion injury (IRI).

Reactive oxygen species (ROS) have pathogenic effects on ischemic-reperfusion injury of heart. Hence, it is important to identify natural antioxidative agents to mitigate such effects. Recently, it has been reported that Clerodendron colebrookianum (CC) leaf extract has antioxidant and hypolipidemic effects in experimental animals. The aim of this study was to examine whether acute treatment with CC extract offers protection against ischemic-reperfusion injury (IRI) and IRI-induced changes in endogenous antioxidant enzyme activities of rat heart. Isolated rat hearts were perfused using the Langendorff's technique, and 20 min of global ischemia was followed by 40 min of reperfusion. Lipid peroxidation after the ischemic-reperfusion episode was significantly reduced in the CC extract-treated heart compared to the control group and suppressed the leakage of lactate dehydrogenase (LDH) during reperfusion. Moreover, CC extract diminished the depletion of myocardial antioxidant enzymes (SOD, Catalase, GSH and GPx) after ischemia-reperfusion. Furthermore, IRI-induced cellular damage was significantly less in CC extract treated myocytes. These results indicate that CC leaf extract protects against oxidative stress and cellular injury associated with ischemic-reperfusion injury of rat heart and suggests that the protective effects of CC extract depend on its antioxidant properties.

Animals↗

Neoadjuvant chemotherapy for epithelial ovarian cancer--role of apoptosis.

BACKGROUND: Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage. Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression. Little is known about the effect of various treatment regimens on the distribution of molecular markers of apoptosis in epithelial ovarian cancer. The objective of this study was to compare the expression levels of both proapoptotic and antiapoptotic proteins p53, p73, Bcl-2, Bcl-XL and survivin in the ascitic cells and tumor samples of patients undergoing treatment with two different regimens. METHODS: A total of 24 patients with untreated epithelial ovarian cancer were randomized into two groups of 12 each. Group 1 patients received three cycles of chemotherapy prior to surgery and three cycles after surgery and group 2 patients received six cycles of chemotherapy prior to surgery. The expression of apoptosis-related proteins was analyzed in ascitic fluid and tumor samples by Western blotting and immunohistochemistry. The apoptotic index was also determined in these samples by the TUNEL assay. RESULTS: Significant decreases in antiapoptotic bcl-2 and survivin were seen, accompanied by increases in apoptotic index in tumors that had undergone chemotherapy as compared to the baseline ascites samples. No significant change in bcl-XL was observed. A significant decrease in proapoptotic p53 was also seen. No expression of p73 was observed in tumors or ascites. The findings were similar in groups 1 and 2 patients and were not statistically significantly different, perhaps due to the small sample size (n=12) of each group. CONCLUSIONS: The above findings indicate that chemotherapy in ovarian carcinoma leads to an increase in apoptosis by a p53-independent pathway, which involves the downregulation of antiapoptotic Bcl-2 and survivin but not Bcl-XL. Furthermore, administering neoadjuvant chemotherapy (six cycles) as an alternative form of therapy for advanced epithelial ovarian cancer is more effective in inducing apoptosis than three cycles. However, the findings of this study need to be corroborated using a larger sample.

Adult↗

Fibrillary glomerulonephritis presenting as rapidly progressive renal failure in a young female: a case report.

Fibrillary Glomerulonephritis (FGN) is a rare clinical entity presenting in majority of patients with nephrotic range proteinuria, microscopic hematuria, impaired renal function and hypertension. The mean age of presentation is reported to be beyond 50 years with 50 patients developing end stage renal disease within a few years. A 28-year-old female presented to us with non-nephrotic range proteinuria, rapidly progressive renal failure (RPRF), microscopic hematuria and mild hypertension. The patient had undergone a renal biopsy at a peripheral center, which was reported as membranoproliferative glomerulonephritis (MPGN) and was being treated with steroids without any benefit. The patient on re-biopsy at our center was diagnosed as FGN on electron microscopy (EM). The patient responded to intravenous pulse methylprednislone and oral cyclophosphamide and is off dialysis for 10 months now. This case highlights the varied clinical and histological presentations of FGN which makes the disease difficult to diagnose more so, in a country like ours where EM is available in only a few centers. An accurate diagnosis aided by high index of clinical suspicion and EM can help in the initiation of appropriate therapy, thereby improving the outcome in this disease which otherwise has a poor prognosis.

Adult↗

Chronic oral administration of Ocimum sanctum Linn. augments cardiac endogenous antioxidants and prevents isoproterenol-induced myocardial necrosis in rats.

Wistar rats (200-250 g) of either sex were fed with fresh leaf homogenate of Ocimum sanctum by oral gavage in two different doses, 50 mg kg-1(Os 50) and 100 mg kg-1 (Os 100), daily for 30 days. This was followed by isoproterenol administration (85 mg kg-1 s.c. two doses at 24h intervals) in both control and 0. sanctum-fed rats to induce myocardial necrosis. Hearts were isolated for estimation of endogenous myocardial antioxidants (superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione peroxidase (GPx) and myocardial lipid peroxidation) and light microscopic study. Increased basal myocardial antioxidant SOD (9.3 +/- 1.2 vs 3.7 +/- 0.7 units mg-1 protein; P<0.05) and catalase activities (34.3 +/- 5.4 vs 17.9 +/- 5.1 units mg-1 protein; P< 0.05) were observed in the Os 50 group only without any evidence of cellular injury in both the groups. In control rats, isoproterenol administration caused significant depletion of myocardial SOD (1.7 +/- 0.2 units mg-1 protein) and GPx (104 +/- 2mU mg-1 protein) activities and increase in GSH (551.7 +/- 30.9, microg g-1 wet weight of tissue) level, with evidence of myocardial necrosis. Isoproterenol-induced changes in myocardial SOD, GPx and GSH were prevented by both the doses of 0. sanctum, however cellular injury was minimal only with 50mg kg-1. The results indicate that long-term feeding of 0. sanctum offered significant protection against isoproterenol-induced myocardial necrosis through a unique property of enhancement of endogenous antioxidants.

Adrenergic beta-Agonists↗

Dietary palm olein oil augments cardiac antioxidant enzymes and protects against isoproterenol-induced myocardial necrosis in rats.

Wistar rats, 150-200 g, of either sex, were fed daily with commercial rat diet supplemented with palm olein oil in two doses (5% v/w (n = 16) and 10% v/w (n = 16) of diet) for 30 days. Control rats (n = 16) were fed with normal diet. On the 29(th) and 30(th) days, 8 rats from each group were administred isoproterenol (85 mg/kg, s.c., 24-h interval). On the 31(st) day, all rats were sacrificed and myocardial tissues were studied for thiobarbituric acid reactive substances (TBARS), antioxidant enzymes and light microscopic changes, along with the ferric-reducing ability of plasma (FRAP). A significant rise in myocardial superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activity and FRAP level were observed in rats fed with palm olein oil. Isoproterenol caused an increase in myocardial oxidative stress in control rats, as evidenced by an increase in myocardial TBARS level, reduction in FRAP and myocardial SOD, catalase and GPx activity, along with focal necrosis of cardiac muscle fibres on light microscopy. The rise in myocardial TBARS and depletion of SOD and catalase activity following isoproterenol administration were prevented in palm-olein-oil-supplemented diet-fed rats at both doses. Isoproterenol-induced myocardial light-microscopic changes were also prevented in the treated groups. The results suggest that dietary palm olein oil caused augmentation of myocardial antioxidant enzymes and protected against isoproterenol-induced myocardial necrosis and associated oxidative stress.

Animals↗

Terminalia arjuna (Roxb.) protects rabbit heart against ischemic-reperfusion injury: role of antioxidant enzymes and heat shock protein.

The bark of Terminalia arjuna Roxb. (TA) is widely recommended for the treatment of ischemic heart disease (IHD) in Indian system of medicine. Oral administration of TA for 12 weeks in rabbits caused augmentation of myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) along with induction of heat shock protein72 (HSP72). In vivo ischemic-reperfusion injury induced oxidative stress, tissue injury of heart and haemodynamic effects were prevented in the TA treated rabbit hearts. The study provides scientific basis for the putative therapeutic effect of TA in ischemic heart disease.

Animals↗

Unusual presentation of lupus nephritis.

We report a male patient who presented with pyrexia, generalized lymphadenopathy, hepatosplenomegaly, and pleural effusion with no cutaneous or musculoskeletal symptoms. Despite extensive investigation, no cause was detected. His initial serology was also negative for autoantibodies. The patient was placed on a trial of antitubercular treatment in view of a positive Mantoux test. His disease evolved into the full clinical picture of systemic lupus erythematosus with nephritis (World Health Organisation class IV) and strongly positive antinuclear antibody and dsDNA over a period of months. He was treated successfully with intravenous cyclophosphamide pulses along with oral prednisolone, and the disease was still in remission after 3 years of follow-up.

Adult↗

Emblica officinalis causes myocardial adaptation and protects against oxidative stress in ischemic-reperfusion injury in rats.

The fruits of Emblica officinalis (Amla) are widely used in the Indian System of Medicine and are believed to increase defense against disease. In the present study, the effects of chronic oral administration of fresh fruit homogenate of Amla on: (i). myocardial antioxidant system and (ii). oxidative stress induced by ischemic-reperfusion injury (IRI) in rat heart were investigated. Fresh amla fruit homogenate, in three different doses (250, 500 and 750 mg/kg) and normal saline (C) were administered orally to Wistar albino rats (120-150 gms) of either sex daily for 30 days. There was reduction in basal myocardial lipid peroxidation, as evidenced by decreased thiobarbituric acid reactive substances (TBARS) level, and augmentation of myocardial endogenous antioxidants, like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in the treated rats. Hearts were also subjected to in vitro IRI (9 min of global ischemia, followed by 12 min of reperfusion, Langendorff's mode). Significant myocyte injury and rise in myocardial TBARS along with depletion of SOD, catalase, GSH (reduced glutathione) and GPx occurred in the control group. No significant increase in myocardial TBARS and depletion of antioxidant enzymes were observed in the treated groups. Myocyte injury was evident only in 250 mg/kg group. The results indicate that chronic Emblica officinalis administration causes myocardial adaptation by augmenting endogenous antioxidants and protects rat hearts from oxidative stress associated with ischemic-reperfusion injury.

Administration, Oral↗

Association of complement receptor 1 (CR1, CD35, C3b/C4b receptor) density polymorphism with glomerulonephritis in Indian subjects.

Complement receptor 1 (CR1, CD35, C3b/C4b receptor), a polymorphic membrane bound glycoprotein is important both as a complement regulatory protein, and as a vehicle for immune complex clearance. It is differentially expressed on erythrocytes, eosinophils, monocytes, B and T-lymphocytes, dendritic cells and kidney podocytes. It also occurs in the plasma as soluble CR1 (sCR1) and in urine as urinary CR1 (uCR1). Different population studies have either suggested or refuted the functional and physiological significance of genomic (HH, high erythrocyte CR1 expression; HL, intermediate and LL, low expression) polymorphism of CR1 in health and disease. Prevalence of autoimmune disorders like RA, GN and SLE is higher in Asian-Indians compared to the western world. Although several studies from India emphasize the modulation of E-CR1 levels as a key factor in the pathophysiology of glomerulonephritis (GN), none of them, however, provide much information on the role of CR1 gene variance in this context. We, therefore, carried out the study of CR1 polymorphism in 117 normal Indian subjects and 65 patients suffering from glomerulonephritis in order to study its possible association with the disease and E-CR1 levels. This is the first study of its kind in the Indian population, in which, the direct effect of a particular genotype on the E-CR1 levels and its possible association with the disease has been studied simultaneously.

Adult↗

Differential expression of CXCR4 receptor in early and term human placenta.

Chemokines and their receptors play a crucial role in regulation of T-cell migration and differentiation. Recent findings suggest that these proteins can also regulate cell functions such as angiogenesis and proliferation. Besides, CXCR4, a chemokine receptor, is one of the two major co-receptors for entry of the HIV virus during the late stages of HIV infection. We have studied the expression of CXCR4 in early (8-10 weeks) and term human placenta. Immunofluorescence staining and RT-PCR analysis revealed a differential expression of the CXCR4 receptor. Densitometric analysis revealed a two fold higher expression of the CXCR4 mRNA in early as compared to term placenta. This finding suggests that the expression of CXCR4 receptor may be developmentally regulated and its role in the early stages of pregnancy is implicated, when embryogenesis and organogenesis takes place. The fact that only 1-2 per cent of the placental transmission of the HIV virus takes place in the early placenta may also be correlated with our findings, suggesting that CXCR4 may not have a direct role in the transmission of HIV infection in the placenta.

Adult↗

Computer based receptogram approach: an objective way of assessing immunohistochemistry of androgen receptor staining and its correlation with hormonal response in metastatic carcinoma of prostate.

AIMS: To categorise the immunostaining heterogeneity of androgen receptors in metastatic carcinoma of the prostate using a pattern oriented approach and to correlate the results with response to hormonal treatment. METHODS: Paraffin wax embedded tumour sections from 85 patients with metastatic carcinoma of the prostate were processed for immunocytochemistry and stained for the androgen receptor using antiandrogen receptor antibodies. A computer based image analysis system was used to analyse the pattern of nuclear immunostaining in a minimum of 500 nuclei/slide. Depending on the nuclear receptor content and concentration, receptogram patterns were established for each specimen. The receptogram pattern was correlated with clinical response to hormonal treatment. RESULTS: Clinical response to hormonal treatment was documented using prostate specific antigen as the marker into responders (good, fair, stable) and non-responders. Forty four of 48 patients who responded to hormonal treatment had type 1 (35) or type 3 (nine) receptograms, which are characterised by a unimodal peak or multimodal peaks within a narrow concentration range. Thirteen of the 18 patients who stabilised had type 1 or type 3 receptograms. Seventeen of the 19 patients who did not respond to hormonal treatment had either type 2 or type 4 receptograms, which are characterised by skewed or bimodal androgen receptor distribution. Positive and negative predictive values of receptograms were 96.5% and 63%, respectively. CONCLUSIONS: Image analysis of androgen receptor immunostaining with a receptogram oriented approach provides important prognostic information that can be used to predict response to hormone treatment in patients with metastatic carcinoma of the prostate.

Aged↗

Modulation of urinary CR1 in systemic lupus erythematosus.

The decline in the levels of erythrocyte complement receptor 1 (ECR1) in systemic lupus erythematosus (SLE) has been widely reported. The most probable cause for this decline is excessive proteolytic shedding of CR1 from the cell surface. Similarly a decline in glomerular CR1 (GCR1) has also been reported in SLE. Because CR1 is excreted in urine it is imperative to study the relationship of urinary CR1 (uCR1) with ECR1 and GCR1, and their overall correlation with disease activity. We have determined the levels of uCR1, ECR1 and GCR1 in SLE patients and compared them with normal controls and minimal change disease (MCD) patients. We found a significant decline in both uCR1 and GCR1 in SLE but not in MCD; levels of uCR1 in MCD were either comparable to those of controls or higher. Immunofluorescence for GCR1 was very high in MCD. We did not find any correlation between ECR1, uCR1 and kidney function tests on divariate scatter analyses. The correlation coefficient for uCR1 and GCR1 was highly significant and positive. Our findings thus suggest that uCR1 reflects the levels of GCR1 expression, which decline drastically in SLE. Therefore we envisage uCR1 as a potential marker for glomerular involvement in SLE.

Case-Control Studies↗

Frequency and role of hepatitis-C virus and type II cryoglobulinemia in membranoproliferative glomerulonephritis.

BACKGROUND: Many studies have claimed a major role of chronic hepatitis-C virus (HCV) infection in immune-mediated diseases such as membranoproliferative glomerulonephritis (MPGN). Chronic HCV infection is also known to produce essential mixed cryoglobulinemia (EMC), which in turn may manifest as vasculitis and cryoglobulinemic MPGN. OBJECTIVE: The aim of the study therefore, was to determine frequency of association and pathogenetic role of HCV infection as well as that of EMC in MPGN patients. METHODS: Fifty-three adult patients of MPGN were studied for HCV, HBsAg, EMC, C3, anti-nuclear antibody (ANA), rheumatoid factor serologically. Histopathology, immunofluorescence (IF) were conducted in all patients and electron microscopy (EM) in those who were found HCV positive. Simultaneously 37 follow-up patients of HCV associated chronic hepatitis were investigated for EMC, renal functions and urinalysis done for evidence of glomerulonephritis (GN). RESULTS: Thirteen percent MPGN patients were HCV positive, however, no viral particle could be seen in electron microscopy in glomeruli of these patients. There was no serologic evidence of HCV induced immune complex GN. None of the MPGN patients showed cryoglobulinaemia. Similarly none from HCV associated chronic hepatitis group had EMC nor showed evidences of glumerulonephritis. CONCLUSION: Thirteen percent of adult MPGN patients in north India were seropositive for HCV, indicating significant association. However, clear evidence in favour of its pathogenetic role was lacking in our study. Secondly, this study reveals that MPGN is non-cryoglobulinemic and HCV is not a major cause in our population compared to what is reported from other countries. These observations need confirmation by a larger study.

Adult↗

Chronic oral administration of raw garlic protects against isoproterenol-induced myocardial necrosis in rat.

Wistar albino rats (150-200 g) were fed raw garlic homogenate orally in three different doses (125, 250, 500 mg/kg/day) for 30 days. Isoproterenol (85 mg/kg, s.c. 2 doses at 24-h interval, animals sacrificed after 24 h of last injection) induced myocardial necrosis in control rats and after 30 days of garlic feeding. Myocardial oxidative stress was evident following isoproterenol administration by reduction in myocardial superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities along with a rise in plasma thiobarbituric acid reactive substances (TBARS). Myocardial necrosis was evident from the light microscopic and ultrastructural changes, along with a rise in plasma lactate dehydrogenase (LDH). Significant preservation of myocardial SOD activity was observed in all the garlic-fed rats. However, there was no significant change in myocardial reduced glutathione level and GPx activity in any of the treated groups. Significant reduction in plasma TBARS and LDH levels was observed in the 500 mg/kg garlic treated group. Isoproterenol-induced myocardial morphological changes were least in the 250 and 500 mg/kg garlic treated groups. The results suggest that chronic oral administration of raw garlic offered protection against isoproterenol-induced myocardial necrosis and associated oxidative stress.

Animals↗

Comparative evaluation of grading of breast carcinomas in fine needle aspirates by two methods.

BACKGROUND & OBJECTIVES: Fine needle aspiration (FNA) material is increasingly being used to determine various prognostic parameters in patients with carcinoma breast. It was recommended that cytological grading should be part of all FNA reports of breast carcinoma so that preoperative prognostication could be done on it. However, the most reliable method for cytological grading that closely reflects the most widely used histological grading system is yet to be determined. This study was undertaken to compare results of two cytological grading methods to see which corresponded better to the histological grade. METHODS: In a double-blind study, cytological grading of 52 patients with breast carcinoma was carried out using two different grading systems (Robinson's and Mouriquand's methods) and the grades compared with the histological grading to find out which reflected histological grades more closely. RESULTS: By Robinson's method 28.8, 46.2 and 25 per cent aspirates were graded as I, II and III respectively. Using Mouriquand's grading 9.6, 69.2 and 21.2 per cent aspirates were graded correspondingly. Comparison of the two methods showed a concordance in 40 (76.9%) cases. Both cytological grading systems showed a concordance of 71.2 per cent with the histological grading. Robinson's cytological grading showed a diagnostic accuracy of 80.76 per cent with 77.77 per cent specificity while Mouriquand's method had an accuracy of 84.60 per cent with 33.33 per cent specificity. INTERPRETATION & CONCLUSION: Though the Robinson's and Mouriquand's grading systems were found to have similar concordance with histological grading, Robinson's method was considered better because of its simplicity, and specificity.

Biopsy, Fine-Needle↗