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Biomedical subjects

R Gupta

Publications and source records attributed to R Gupta.

At least 55 records · Page 3Linked to original sources

Management issues in the metabolic syndrome.

The metabolic syndrome or cardiovascular dysmetabolic syndrome is characterized by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and hypertension. The major risk factors leading to this syndrome are physical inactivity and an atherogenic diet and cornerstone clinical feature is abdominal obesity or adiposity. In addition, patients usually have elevated triglycerides, low HDL cholesterol, elevated LDL cholesterol, other abnormal lipid parameters, hypertension, and elevated fasting blood glucose. Impaired fibrinolysis, increased susceptibility to thrombotic events, and raised inflammatory markers are also observed. Given that India has the largest number of subjects with type-2 diabetes in the world it can be extrapolated that this country also has the largest number of patients with the metabolic syndrome. Epidemiological studies confirm a high prevalence. Therapeutic approach involves intervention at a macro-level and control of multiple risk factors using therapeutic lifestyle approaches (diet control and increased physical activity, pharmacotherapy - anti-obesity agents) for control of obesity and visceral obesity, and targeted approach for control of individual risk factors. Pharmacological therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. Anti-obesity drugs such as sibutramine and orlistat can be tried to reduce weight and central obesity and jointly control the metabolic syndrome components. Other than weight loss, there is no single best therapy and treatment should consist of treatment of individual components of the metabolic syndrome. Newer drugs such as the endocannabinoid receptor blocker,rimonabant, appear promising in this regard. Atherogenic dyslipidemia should be controlled initially with statins if there is an increase in LDL cholesterol. If there are other lipid abnormalities then combination therapy of statin with fibrates, nicotinic acid, or ezetimibe should be considered. For insulin resistance, drugs such as thiazolidinediones and renin-angiotensin system blockers are available. Available evidence suggests that angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBS) may be more beneficial for treatment of hypertension in patients with metabolic syndrome compared to others as these drugs also prevent development of diabetes. Patients with metabolic syndrome also have elevations in fibrinogen and other coagulation factors leading to prothrombotic state and aspirin may be beneficial for primary prevention in these patients. The new developments in the treatment of metabolic syndrome with drugs, such as peroxisome proliferator-activated receptor (PPAR) agonists and cannabinoid receptor-1 antagonists, will broaden the horizons of the current treatment options. Fixed-dose combination polypharmacy using a single pill is an interesting concept that needs to be evaluated in long-term prospective trials in such patients.

Diet↗

Long-term outcomes of laparoscopic surgery for colorectal cancer.

Multiple reports have outlined the potential benefits of the laparoscopic approach to colon surgery. Recently, randomized control trials have demonstrated the safety of applying these techniques to colorectal cancer. This study examined the long-term follow-up assessment of patients after laparoscopic colorectal cancer resections and compared them with a large prospective database of open resections. A total of 231 resections were performed for adenocarcinoma of the colon or rectum between 1992 and 2004. Of these 231 resections, 93 were rectal (40.3%) and 138 were colonic (59.7%). A total of 8 (3.2%) of the resections were performed as emergencies, and 27 (11.7%) were converted to open surgery. The mean follow-up period was 35.84 months (range, 0-132 months). The disease recurred in 51 of the patients (22.1%) before death, involving 14 (6.1%) local and 37 (16%) distant recurrences. Only two patients had wound recurrences (0.8%), and both patients had widespread peritoneal recurrence at the time of diagnosis. The overall survival rate was 65.3% at 60 months and 60.3% at 120 months. The disease-free survival rate was 58% at 60 months and 56% at 120 months. Laparoscopic techniques can be applied to a wide range of colorectal malignancies without sacrificing oncologic results during a long-term follow-up period.

Adenocarcinoma↗

Purification and properties of a novel extra-cellular thermotolerant metallolipase of Bacillus coagulans MTCC-6375 isolate.

A novel extra-cellular lipase from Bacillus coagulans MTCC-6375 was purified 76.4-fold by DEAE anion exchange and Octyl Sepharose chromatography. The purified enzyme was found to be electrophoretically pure by denaturing gel electrophoresis and possessed a molecular mass of approximately 103 kDa. The lipase was optimally active at 45 degrees C and retained approximately 50% of its original activity after 20 min of incubation at 55 degrees C. The enzyme was optimally active at pH 8.5. Mg2+, Cu2+, Ca2+, Hg2+, Al3+, and Fe3+ at 1mM enhanced hydrolytic activity of the lipase. Interestingly, Hg2+ ions resulted in a maximal increase in lipase activity but Zn2+ and Co2+ ions showed an antagonistic effect on this enzyme. EDTA at 150 mM concentration inhibited the activity of lipase but Hg2+ or Al3+ (10mM) restored most of the activity of EDTA-quenched lipase. Phenyl methyl sulfonyl fluoride (PMSF, 15 mM) decreased 98% of original activity of lipase. The lipase was more specific to p-nitrophenyl esters of 8 (pNPC) and 16 (pNPP) carbon chain length esters. The lipase had a Vmax and Km of 0.44 mmol mg(-1)min(-1) and 28 mM for hydrolysis of pNPP, and 0.7 mmol mg(-1)min(-1) and 32 mM for hydrolysis of pNPC, respectively.

Bacillus↗

Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer.

BACKGROUND: In the prostate, conversion of testosterone to dihydrotestosterone (DHT), by the enzymes 5alpha-reductase types 1 and 2 (5alphaR1, 5alphaR2) is required for normal growth and probably also for development of prostate cancer (PCa). Finasteride, a 5alphaR2 inhibitor, was shown to reduce the prevalence of PCa in the Prostate Cancer Prevention Trial. However, inhibition of both 5alphaR isoenzymes causes a greater decrease in serum DHT. The aim of this study was to assess differential expression of these enzymes at various stages of PCa development. METHODS: Immunostaining for 5alphaR1 and 5alphaR2, using specific, well-validated antibodies, was evaluated in 26 benign prostatic hyperplasia (BPH) (16 for 5alphaR2), 53 primary PCa (21 for 5alphaR2), 18 prostatic intraepithelial neoplasia (PIN), 12 primary PCa treated with neoadjuvant androgen ablation, 15 locally recurrent PCa specimens, and 18 PCa metastases. RESULTS: The mean area of moderate plus high intensity staining for 5alphaR1 increased from 4.8 +/- 2.8% of total epithelial area in BPH, to 18.9 +/- 5.7% in PIN, 17.0 +/- 3.2% in primary cancer, 38.0 +/- 7.3% in recurrent cancer, and 55.8 +/- 8.5% in PCa metastases. The mean staining area for 5alphaR2 decreased from 58.8 +/- 7.2% in BPH, to 21.1 +/- 5.5% in PIN and 34.8 +/- 6.7% in primary PCa. Staining for 5alphaR2 was increased in recurrent cancer and PCa metastases compared to primary PCa, at 58.7 +/- 5.2% and 69.2 +/- 8.7%, respectively. CONCLUSIONS: 5alphaR1 immunostaining is increased and 5alphaR2 immunostaining is decreased during development of PCa. In addition, there is increased expression of both 5alphaR isozymes in recurrent and metastatic cancers, suggesting that both isozymes may be important in the development and progression of PCa.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

gamma-L-glutamyltaurine.

The discovery of the dipeptide gamma-glutamyltaurine (gamma-GT; glutaurine, Litoralon) in the parathyroid in 1980 and later in the brain of mammals gave rise to studies on intrinsic and synthetic taurine peptides of this type. It was suggested that gamma-glutamyltransferase (GGT; gamma-glutamyltranspeptidase) in the brain is responsible for the in vivo formation of this unusual dipeptide. gamma-GT has been prepared by both synthetic and enzymatic methods. The chemical syntheses included the use of protecting groups and coupling methods. A wide spectrum of analytical and spectroscopic methods was used to confirm the structure of the synthetic compounds and to elucidate the position of the peptide bond. Enzymatic preparation of gamma-GT from taurine takes advantage of the selective transpeptidation action of GGT on L-glutamine, glutathione, gamma-glutamyl-p-nitroanilide or other glutamine donors. Although the functional roles of gamma-GT in the brain are only poorly understood, many of its established CNS effects have been reported in the last 25 years. Its effect on emotional arousal and its anti-conflict potencies are synergistic with the anxiolytic drug diazepam. gamma-GT exhibits anti-conflict potency, which is exerted by reducing aversion or phobia and/or the anxiety levels. gamma-GT also acts as endogenous modulator in excitatory aminoacidergic neurotransmission. It is suggested that such acidic peptides through N-methyl-D-aspartic acid receptors could be part of the neurochemical substrate underlying self-stimulation of the medial prefrontal cortex. Other gamma-GT effects in neural systems include: effects on the monoamine concentration in the brain; effects on aggressive behavior in the cat; effects on thyroid hormones in the rat; amelioration of electroshock-induced amnesia; potent and long-lasting antiepileptic action (on intra-amygdaloid injection); affect the glutamatergic system in schizophrenic disorders. Roles for gamma-GT in non-neural systems have also been reported, e.g., effects on the metamorphosis of amphibians; on plasma rennin regulation; on radiation protection; on uric acid levels; on human antibody-dependent cell-mediated cytotoxicity (ADCC) and many more.

Amphibians↗

Effect of ethanol variation on the internal environment of sol-gel bulk and thin films with aging.

Sol-gel derived bulk and thin films were prepared from different compositions at low pH ( approximately 2.0) containing varying concentrations of ethanol from 15 to 60% at constant water (H(2)O)/tetraethyl-orthosilicate (TEOS) ratio (R=4). The fluorescence microscopic and spectroscopic measurements on fluorescent probe, Hoechst 33258 (H258) entrapped in these compositions were carried out at different days of storage to monitor the effects of concentration of ethanol on the internal environment of sol-gel materials. Fluorescence microscopic observations on sol-gel thin films, prepared by dip coating technique depicted uniform and cracked surface at withdrawal speed 1cm/min (high speed) and 0.1cm/min (low speed) respectively, which did not change during aging. Fluorescence spectral measurements showed emission maximum of H258 at approximately 535 nm in fresh sols at all concentrations of ethanol which depicted slight blue shift to 512 nm during aging in bulk. No such spectral shift has been observed in sol-gel thin films coated at high speed whereas thin films coated at low speed clearly showed an additional band at approximately 404 nm at 45 and 60% concentration of ethanol after about one month of storage. Analysis of the fluorescence lifetime data indicated single exponential decay (1.6-1.8 ns) in fresh sol and from third day onwards, invariably double exponential decay with a short (tau(1)) and a long (tau(2)) component were observed in sol-gel bulk with a dominant tau(1) at approximately 1.2 ns at all concentrations of ethanol. A double exponential decay consisting of a short component (tau(1)) at approximately 0.2 ns and a long component (tau(2)) at approximately 3.5 ns were observed at all ethanol concentrations in both fresh and aged sol-gel thin films. Further, distribution analysis of lifetimes of H258 showed two mean lifetimes with increased width in aged bulk and thin films. These results are likely to have strong implications in designing the internal environment for applications in biosensors.

Biocompatible Materials↗

Fluorescence spectroscopic studies to characterize the internal environment of tetraethyl-orthosilicate derived sol-gel bulk and thin films with aging.

Characterization of the internal environment of a sol-gel matrix is an important area of investigation in optical biosensors. In the present study, different sol-gel compositions were prepared by varying the water (H2O) to tetraethyl-orthosilicate (TEOS) ratio (R) from 1 to 16 and the changes in the internal environment of the sol-gel both in bulk and thin films as a function of aging (storage) were investigated using fluorescence spectroscopy. We focussed on the fluorescence characteristics , viz. emission and excited state lifetime of Hoechst 33258 (H258), a bisbenzimidazole derivative, which was used as fluorescence probe entrapped in the TEOS derived sol-gel bulk and thin films. These sols were prepared at a low pH (approximately 2.0) and the thin films were coated by dip coating technique at withdrawal speeds of 1 cm/min and 0.1cm/min. Usually, uniform thin films were obtained at a high speed (1 cm/min) and partially cracked film at a low speed (0.1 cm/min) as observed by fluorescence microscope. These observations did not change during aging. On the contrary, three months long observations on steady-state fluorescence emission measurements on H258 depicted a blue shift from 535 nm to 508 nm at R = 1 in the sol-gel bulk, whereas at higher ratios this was not prominent. At all ratios, dual emission bands were observed in thin films. This may be due to faster sol-gel to xerogel transition during aging depending on the ratio (R). Analysis of the excited state decay profiles of H258 revealed a double exponential fitting having a short (tau1) and a long (tau2) component in both fresh and during aging, in the sol-gel bulk and thin films, indicating heterogeneity in the internal environment. The value of tau1 increased from 0.4 ns to 1.2 ns whereas tau2 attained a value from 3.0 ns to 3.6 ns at R = 1 upon aging in the sol-gel bulk. The corresponding values of tau1 and tau2 in thin films were 0.3 ns and 3.5 ns, respectively. The values of these decay components in thin films did not alter much due to storage, but their relative contributions showed more systematic changes in the thin films. The observed changes could be correlated to rigidification in the bulk depending on the ratio (R). This process was very slow at R > or = 4. The heterogeneity in the internal environment of bulk and thin films upon aging appeared to be different as revealed from analysis of excited-state lifetime. Thus, the bisbenzimidazole derivative H258 appears to be very useful probe for characterizing the internal environment of both the sol-gel bulk and thin films.

Luminescent Measurements↗

Neonatal surgical jaundice revisited.

Neonatal hyperbilirubinemia is a common problem in newborn nurseries and manifest clinically as jaundice. Nearly 25-50% of all newborns and a much higher percentage of premature babies develop hyperbilirubinemia. This is mostly physiological, but a small percentage of these babies have pathological jaundice, requiring detailed investigations and management. It is also absolutely essential to consider a possibility of extra-hepatic biliary atresia early, during management of a case of neonatal direct hyperbilirubinemia as early surgical intervention results in a better outcome in EHBA. This article aims to describe the diagnostic approach to neonatal hyperbilirubinemia with special emphasis on conditions requiring surgical intervention also it throws light on present status of EHBA in Indian circumstances.

Bilirubin↗

A multidisciplinary approach to assess erectile dysfunction in high-risk cardiovascular patients.

Erectile dysfunction (ED) is increasingly considered as one manifestation of systemic vascular disease. Accordingly, ED and coronary artery disease share mutual risk factors and frequently coexist. Sexual health is an important aspect of our patients' lives, and ED is a common concern of the cardiovascular patient. Despite this, sexual function is under-addressed in the cardiac patient. Even when this topic is broached by the primary care physician or urologist, ED frequently remains untreated due to safety concerns involving cardiac disease and other comorbidities. This article describes our experience with this unique patient population, as well as our approach to building a multidisciplinary clinic designed to specifically address the important issue of ED in the cardiac patient.

Administration, Oral↗

Decompressive surgery for acute subdural haematoma leading to contralateral extradural haematoma: a report of two cases and review of literature.

Development of a contralateral epidural haematoma during or immediately after cranial surgery is a well-described entity. However, in a case of acute subdural haematoma where the brain is usually tense, postoperative development of contralateral extradural haematoma is uncommon. We report two cases of contralateral extradural haematoma after decompressive surgery for acute subdural haematoma. We recommend routine postoperative CT immediately after cranial surgery for head trauma. This would help in timely detection and treatment of such a complication.

Adult↗

Long-term outcomes of laparoscopic heller cardiomyotomy without an anti-reflux procedure.

Certain technical features of laparoscopic Heller cardiomyotomy (LHM) remain controversial, including the extent of the myotomy and the indication for an antireflux procedure. We completed a retrospective chart review of all patients who underwent LHM for achalasia at 1 tertiary care institution to review our institutional experience with LHM without an antireflux procedure. Forty patients underwent a LHM performed by 2 surgeons, 65% of whom had previous medical management (Botox: 12 patients, LES dilatation: 14). The operating time was significantly increased in patients with Botox injections (98.3 vs. 71.1 minutes, P = 0.005). There were 3 intraoperative complications (mucosal injury in 3 patients, 2 had Botox injections). Postoperative evaluation demonstrated a mean dysphagia score of 0.2, a mean heartburn score of 3.2, and a mean LES pressure of 6.32 mm Hg. Thirty-two patients are maintained on acid-suppressing medications with good control of reflux symptoms. LHM without an antireflux procedure achieves excellent clinical outcomes in most patients with achalasia regardless of previous medical management. Previous medical management may present a greater technical challenge and may place patients at increased risk of mucosal injury.

Adult↗