Biomedical subjects

Amit Dinda

Publications and source records attributed to Amit Dinda.

11 recordsLinked to original sources

PubMed2006

Steroid-responsive nephrotic syndrome in a patient with nail-patella syndrome.

Nail-patella syndrome (NPS) is a rare disorder with autosomal dominant mode of inheritance. We report a child with NPS and steroid-responsive, frequently relapsing nephrotic syndrome. The child had dystrophic nails, flexion contractures of both elbows and normal renal functions. X-rays of the knees and pelvis showed hypoplastic patellae and iliac horns. Renal histology was unremarkable with mild focal increase in mesangial cellularity compatible with minimal change disease. Ultrastructural features of NPS including thickening of the glomerular basement membrane with electron-lucent areas were not found.

Child↗

PubMed2006

Morphine modulates monocyte-macrophage conversion phase.

Monocyte migration and their activation into the macrophage phenotype play a role in the modulation of tissue injury. We studied the effect of morphine on the monocyte-macrophage conversion phase (MMCP). Phorbol 12-myristate 13-acetate (PMA) activated THP-1 cells and promoted their adhesion to the substrate. Morphine inhibited PMA-induced MMCP. However, opiate receptor antagonists attenuated this effect of morphine. Interestingly, PMA as well as morphine-stimulated superoxide production by monocytes. Superoxide dismutase (SOD) not only inhibited PMA-mediated MMCP but also attenuated the inhibitory effect of morphine. PMA not only enhanced adhesion of monocytes to a filter but also promoted their migration. These findings suggest that the PMA-induced macrophage phenotype conversion may be accelerating their migration; whereas, morphine may be preventing the migration of monocytes by inhibiting MMCP.

Cell Adhesion↗

PubMed2006

Morphine-induced degradation of the host defense barrier role of intestinal mucosal injury.

The effect of morphine on intestinal ulcer formation and on the degradation of the host defense barrier was studied. Mice receiving morphine (MRM) showed mucosal ulcer formation in the ileum and in the upper third of the colon. In in vitro studies, morphine enhanced apoptosis of cultured human colonic cells (HCC). Nitric oxide synthase (NOS) inhibitors attenuated the proapoptotic effect of morphine. Moreover, morphine stimulated NO generation by HCCs. MRM also showed a breach in the host defense barrier as well as injury to peritoneal macrophages. Although NOS inhibitors completely prevented morphine-induced intestinal ulcer formation, it provided only partial protection against a breach in the host defense barrier and peritoneal macrophage injury. Propranolol did not inhibit the induction of intestinal ulcer formation in MRM; nevertheless, propranolol prevented a breach in the host defense barrier as well as macrophage injury in MRM, whereas hemin exacerbated macrophage injury as well as the breach in the host defense barrier of MRM. These findings suggest that morphine-induced intestinal injury is mediated through NO generation. However, the degradation of the host defense barrier correlates with macrophage injury, but not intestinal injury.

Animals↗

PubMed2005

Immunomodulatory effect of morphine: therapeutic implications.

The immunosuppressive as well as modulatory effects of morphine have been known in clinical medicine for > 100 years. Recent developments in molecular immunology, including experiments in mu (mu) opioid receptor knockout mice has led to a better understanding of central and peripheral mechanisms involved in this process. Though there is a large volume of literature documenting adverse effects of immunosupression following the use of morphine, several reports confirm its potential usefulness as an immunomodulator. In vitro and in vivo animal experiments have demonstrated wide-spectrum effects of morphine, including anti-inflammatory, antifibrotic, antitumour, cardioprotective and renoprotective. Immunomodulation is an important field in modern medicine with rapid advancement in recent years. Though a final statement regarding the clinical relevance of morphine-induced immunomodulation cannot be made at this juncture, nevertheless, it is worthwhile to review current developments. It may encourage further clinical studies to elucidate the influence of morphine treatment on immune regulation in different specialties of medicine.

Animals↗

PubMed2004

Protective effects of Curcuma longa on ischemia-reperfusion induced myocardial injuries and their mechanisms.

The present study was undertaken to evaluate the cardioprotective potential of Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial infarction (MI). Wistar rats were divided into three groups and received saline orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 treated group) respectively for one month. On the 31st day, rats of the control I/R and Cl treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. I/R resulted in significant cardiac necrosis, depression in left ventricular function, decline in antioxidant status and elevation in lipid perodixation in the control I/R group as compared to sham control. Myocardial infarction produced after I/R was significantly reduced in the Cl treated group. Cl treatment resulted in restoration of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I/R. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by Cl treatment. The beneficial cardioprotective effects also translated into the functional recovery of the heart. Cardioprotective effect of Cl likely results from the suppression of oxidative stress and correlates with the improved ventricular function. Histopathological examination further confirmed the protective effects of Cl on the heart.

Analysis of Variance↗

PubMed2004

Fibrosing cholestatic hepatitis in renal transplant recipient with CMV infection: a case report.

Fibrosing cholestatic hepatitis (FCH) is an uncommon complication of renal transplantation. It is usually associated with hepatitis B and C viral infection. It is further rare in renal transplantation in absence of HBV and HCV infection. To the best of our knowledge, only three cases of FCH in renal transplantation, which were both HBV and HCV negative, have been reported to date. Out of these, two cases were diagnosed to have CMV infection and the third was attributed to azathioprin. We are presenting another case of FCH in a renal transplant recipient with CMV infection.

Adult↗

PubMed2004

Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment.

The efficacy of Withania somnifera (Ws) to limit myocardial injury after ischemia and reperfusion was explored and compared to that of Vit E, a reference standard known to reduce mortality and infarct size due to myocardial infarction. Wistar rats (150-200 g) were divided into six groups and received orally saline (sham, control group), Ws-50/kg (Ws control and treated group) and Vit E-100 mg/kg (Vit E control and treated group) respectively for 1 month. On the 31st day, rats of the control, Vit E and Ws treated groups were anesthetized and subjected to 45 min occlusion of the LAD coronary artery followed by 60 min reperfusion. Hemodynamic parameters: systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), left ventricular peak (+)LVdP/dt and (-)LVdP/dt were monitored. Hearts were removed and processed for histopathological and biochemical studies: Myocardial enzyme viz, creatin phosphokinase (CPK), and antioxidant parameters: malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) were estimated. Postischemic reperfusion produced significant cardiac necrosis, depression of left ventricular functions (MAP, LVEDP, (+) and (-)LVdP/dt) and a significant fall in GSH (p < 0.01), SOD, CAT (p < 0.05), LDH and CPK (p < 0.01) as well as an increase in MDA level (p < 0.05) in the control group rats as compared to sham group. The changes in levels of protein and GPx was however, not significant. Ws and Vit E favorably modulated most of the hemodynamic, biochemical and histopathological parameters though no significant restoration in GSH, MAP (with Vit E) were observed. Ws on chronic administration markedly augmented antioxidants (GSH, GSHPx, SOD, CAT) while Vit E did not stimulate the synthesis of endogenous antioxidants compared to sham. Results indicate that Ws significantly reduced myocardial injury and emphasize the beneficial action of Ws as a cardioprotective agent.

Animals↗

PubMed2004

Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction.

The present study was designed to evaluate the cardioprotective potential of hydro-alcoholic extract of Withania somnifera on the basis of haemodynamic, histopathological and biochemical parameters in the isoprenaline-(isoproterenol) induced myocardial necrosis in rats and to compare with Vitamin E, a known cardioprotective antioxidant. Wistar albino male rats (150-200 g) were divided into six main groups: sham, isoprenaline control, Withania somnifera/Vitamin E control and Withania somnifera/Vitamin E treatment groups. Withania somnifera was administered at doses 25, 50 and 100 mg/kg and Vitamin E at a dose of 100 mg/kg, orally for 4 weeks. On days 29 and 30, the rats in the isoprenaline control and Withania somnifera/Vitamin E treatment groups were given isoprenaline (85 mg/kg), subcutaneously at an interval of 24 hr. On day 31, haemodynamic parameters were recorded and the hearts were subsequently removed and processed for histopathological and biochemical studies. A significant decrease in glutathione (P<0.05), activities of superoxide dismutase, catalase, creatinine phosphokinase and lactate dehydrogenase (P<0.01) as well as increase in lipid peroxidation marker malonyldialdehyde level (P<0.01) was observed in the hearts of isoproterenol control group rats as compared to sham control. However, we have not observed any significant changes in activity of glutathione peroxidase and protein levels. Left ventricular dysfunction was seen as a decrease in heart rate, left ventricular rate of peak positive and negative pressure change and elevated left ventricular end-diastolic pressure in the control group was recorded. On histopathological examination, myocardial damage was further confirmed. Our data show that Withania somnifera (25, 50 and 100 mg/kg) exerts a strong cardioprotective effect in the experimental model of isoprenaline-induced myonecrosis in rats. Augmentation of endogenous antioxidants, maintenance of the myocardial antioxidant status and significant restoration of most of the altered haemodynamic parameters may contribute to its cardioprotective effect. Among the different doses studied, Withania somnifera at 50 mg/kg dose produced maximum cardioprotective effect.

Administration, Oral↗

PubMed2003

Intravenous cyclophosphamide in steroid-resistant nephrotic syndrome.

We prospectively examined the effect of treatment with intravenous cyclophosphamide in patients with steroid-resistant nephrotic syndrome. Twenty-four patients (minimal change disease in 11, focal segmental glomerulosclerosis in 9, and mesangioproliferative glomerulonephritis in 4), who did not show remission of proteinuria despite treatment with 8 weeks of oral prednisolone and six intravenous pulses of dexamethasone, were studied. Cyclophosphamide was administered intravenously, at a dose of 750 mg/m(2) once a month for 6 months; therapy with alternate-day prednisolone was continued. The mean (SD) age at treatment was 7.8 (4.0) years; 18 patients had initial resistance and 6 had late resistance. At the end of 6 months treatment, 7 (29.2%) patients each had complete remission (absent proteinuria, normal serum albumin) and partial remission (1-2+ proteinuria, normal serum albumin). Ten (41.6%) patients showed no response to therapy. The mean time to complete or partial remission, after initiation of treatment with cyclophosphamide, was 2.4+/-1.7 months and 2.7+/-1.8 months, respectively. Most responders (85.8% complete and 57.2% partial responders) achieved remission by the third dose of pulse cyclophosphamide. More patients with late resistance (50%) compared with initial resistance (22.2%) achieved complete remission. Partial remission was transient and lasted for a mean duration of 6.4+/-3.5 months. Serious infections were observed during therapy in 5 patients. On long-term follow-up, 5 (20.8%) patients were in remission, while nephrotic-range proteinuria or end-stage renal disease was seen in 17 (70.8%). Findings from the present study suggest that therapy with intravenous cyclophosphamide has limited efficacy in inducing sustained remission in patients with initial corticosteroid resistance. Sustained remission is likely to occur in a significant proportion of patients with late resistance and those with absence of significant tubulointerstitial changes on renal histology.

Adolescent↗

PubMed2003

Autosomal dominant progressive nephropathy with deafness: linkage to a new locus on chromosome 11q24.

Focal segmental glomerulosclerosis (FSGS) and Alport syndrome (AS) are two major causes of end-stage renal disease (ESRD). A few families with autosomal dominant FSGS have been reported with linkage to chromosome 19q13 or 11q22, while AS is usually linked to mutations in type IV collagen (COL4) subunit genes. A phenotype resembling AS may also be seen with myosin heavy chain-9 (MYH9) gene mutations. This study ascertained a multigeneration family (CHP-177) with clinical aspects of both FSGS and AS where we identified a new locus for the trait. A genome-wide scan was performed with 400 markers, and fine mapping was performed for chromosome 11 markers. Data were analyzed by GENEHUNTER and VITESSE under various models. CHP-177 is a 39-member kindred residing near New Delhi, India, with seven affecteds and showed male-to-male transmission. Two members had ESRD. Renal biopsies showed both FSGS lesions and thin glomerular basement membranes. Five of the affecteds also had sensorineural deafness, which involved both low and high frequency in some members. The AS loci, i.e., COL4A3/COL4A4 and MYH9 (LOD scores: -6.1 and -4.3, respectively) and FSGS loci, on 19q13 and 11q22, were excluded from linkage. A significant evidence of linkage was observed for 11q24 region, with a multipoint LOD (z-score) of 3.2 for marker D11S4464 at theta = 0. The z-1 confidence interval for the linked region spans a genetic distance of 7 cM. This study thus reports an autosomal dominant nephropathy with features of both FSGS and AS in which linkage to currently known loci for such phenotypes was excluded and a new locus on 11q24 was identified. The findings suggest further locus heterogeneity for the autosomal dominant nephropathy phenotype.

Adolescent↗

PubMedDate not supplied

An assessment of the role of reactive oxygen species and redox signaling in norepinephrine-induced apoptosis and hypertrophy of H9c2 cardiac myoblasts.

Cardiac myocytes, upon exposure to increasing doses of norepinephrine (NE), transit from hypertrophic to apoptotic phenotype. Since reactive oxygen species (ROS) generation is attributed to both phenomena, the authors tested whether an elevation in intracellular ROS level causes such transition. H9c2 cardiac myoblasts upon treatment with hypertrophic and apoptotic doses of NE (2 and 100 microM, respectively) transiently induced intracellular ROS at a comparable level, while 200 microM H(2)O(2), another proapoptotic agonist, showed robust and sustained ROS generation. Upon analysis of a number of redox-responsive transcription factors as the downstream targets of ROS signaling, the authors observed that NE (2 and 100 microM) and H(2)O(2) (200 microM) were ineffective in inducing NF-kappaB while both the agonists upregulated AP-1 and Nrf-2. However, the extents of induction of AP-1 and Nrf-2 were not in direct correlation with the respective ROS levels. Also, AP-1 activities induced by two doses of NE were intrinsically different, since at 2 microM, it primarily induced FosB, and at 100 microM it activated Fra-1. Differential induction of FosB and Fra-1 was also reiterated in adult rat myocardium injected with increasing doses of NE. Therefore, NE induces hypertrophy and apoptosis in cardiac myocytes by distinct redox-signaling rather than a general surge of ROS.

Adrenergic alpha-Agonists↗