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Biomedical subjects

Ashok Kumar

Publications and source records attributed to Ashok Kumar.

53 records · Page 3Linked to original sources

Pancreatic abscess: 10 years experience.

BACKGROUND: Secondary infections of pancreatic and peripancreatic necrosis account for most of the deaths following acute pancreatitis. These infections occur in the form of 'infected pancreatic necrosis' and 'pancreatic abscess'. The latter is a rare complication of acute pancreatitis in comparison with the former. METHODS: Twenty-one patients with pancreatic abscess were managed over a 10-year period at a tertiary care centre in Northern India. The present report details the clinical profile, investigations performed and management strategy (surgery and intervention radiology) of these patients. The role of surgery and percutaneous catheter drainage (PCD) in the management of pancreatic abscess is discussed, with emphasis on the successful outcome seen in a properly selected group of patients managed by PCD. RESULTS: Of the 21 patients, 12 were managed by percutaneous intervention, nine were managed surgically (of these, two had a prior PCD) and two patients were managed conservatively. The overall mortality was 9.5% (2/21). Thus, percutaneous management was suitable for 57% patients, was successful in 83.3%, with a mortality of 8.3%. Surgical therapy alone was offered to 33% of patients, was successful in 85.7%, with a mortality of 14.2%. Complications were seen in four of the nine patients managed by percutaneous drainage alone and eight of the nine patients managed surgically. CONCLUSIONS: Pancreatic abscess is a potentially lethal complication in patients recovering from acute pancreatitis. Early diagnosis and prompt intervention with careful selection of patients based on computed tomography imaging for surgical or percutaneous radio-logical management, is met with a successful outcome in a majority of patients. The roles of surgery and PCD are complementary.

Abscess↗

Evaluation of an antimicrobial-impregnated continuous ambulatory peritoneal dialysis catheter for infection control in rats.

Infection is the most serious complication arising in long-term continuous ambulatory peritoneal dialysis (CAPD), specifically peritonitis and exit-site infection. The initial weeks after implantation is the crucial period during which bacterial colonization of the catheter results in maximal morbidity, with Staphylococcus aureus being the most virulent organism. We developed an antimicrobial-impregnated CAPD catheter by impregnating the cuff and tubing with chlorhexidine, silver sulfadiazine, and triclosan in a polymer matrix. The antimicrobial spectrum and duration were shown by measuring zones of inhibition to various bacteria and fungi over the course of 5 to 10 days. Activity also was assessed subsequent to soaking in trypticase soy broth containing 20% bovine serum over the course of 1, 3, and 7 days. Significant antimicrobial activity was shown against all organisms tested for, with particular efficacy against gram-positive bacteria. Catheters were implanted in rats followed by inoculation of the exit site with S aureus. Seven days postimplantation, 0% of the impregnated catheters were colonized intraperitoneally compared with 100% of the control catheters. Similarly, 12.5% of the impregnated catheters were colonized at the exit site, whereas 100% of the controls were colonized. Histologic analysis showed that this combination and concentration of antimicrobials did not retard healing or cause increased inflammation compared with control catheters after 3, 10, and 24 days postimplantation in noninoculated rats.

Animals↗

Differential conformational environment of tryptophan in epsilon native prototoxin and active toxin from Clostridium perfringens type D.

The tryptophan content of Clostridium perfringens type D epsilon protoxin and toxin was found to be one residue per molecule of protein. N-bromosuccinimide in the presence of urea cleaves the tryptophan with total loss of lethality in both toxin and prototoxin. Fluorescence spectroscopy, circular dichroism (CD) and 10% ethylene glycol solvent perturbation studies showed that the tryptophan in epsilon toxin and that in prototoxin have different conformational environments. The tryptophan is more on the surface in the prototoxin than in the toxin molecule. NBS causes total loss of lethality of the toxin with its ellipticity coming to almost zero in the near UV region of the CD.

Animals↗

Nef protein of human immunodeficiency virus and lipopolysaccharide induce expression of CD14 on human monocytes through differential utilization of interleukin-10.

We investigated the expression of membrane-bound CD14 (mCD14) on monocytes and soluble CD14 (sCD14) released into the culture supernatants of peripheral blood lymphocytes (PBMC) from human immunodeficiency virus (HIV)-infected individuals. Monocytes from HIV-positive individuals exhibited both enhanced mCD14 expression and sCD14 production in the PBMC culture supernatants compared to the levels of mCD14 and sCD14 in HIV-negative individuals. This enhanced mCD14 expression and sCD14 production in HIV-infected individuals may be due to the effects of cytokines, the bacterial product lipopolysaccharide (LPS), and/or the HIV regulatory antigens Tat and Nef. Interleukin-10 (IL-10), an immunoregulatory cytokine, as well as LPS enhanced mCD14 expression and the release of sCD14 in the culture supernatants. HIV-Nef, unlike Tat, enhanced mCD14 expression on monocytes but did not induce the release of sCD14 into the culture supernatants. Studies conducted to investigate the mechanism underlying HIV-Nef-induced mCD14 expression revealed that HIV-Nef upregulated mCD14 expression via a mechanism that does not involve endogenously produced IL-10. In contrast, LPS upregulated the expression of mCD14 and increased the release of sCD14 via a mechanism that involves, at least in part, endogenously produced IL-10. Furthermore, dexamethasone, an anti-inflammatory and immunosuppressive agent, inhibited HIV-Nef-induced CD14 expression in an IL-10-independent manner. In contrast, dexamethasone inhibited IL-10-dependent LPS-induced CD14 expression by interfering with IL-10-induced signals but not by blocking IL-10 production. These results suggest that HIV-Nef and IL-10 constitute biologically important modulators of CD14 expression which may influence immunobiological responses to bacterial infections in HIV disease.

Adult↗

17beta-estradiol benzoate decreases the AHP amplitude in CA1 pyramidal neurons.

Disruption of Ca(2+) homeostasis is hypothesized to mediate several electrophysiological markers of brain aging. Recent evidence indicates that estradiol can rapidly alter Ca(2+)-dependent processes in neurons through nongenomic mechanisms. In the current study, electrophysiological effects of 17beta-estradiol benzoate (EB) on the Ca(2+)-activated afterhyperpolarization (AHP) were investigated using intracellular sharp electrode recording in hippocampal slices from ovariectomized Fischer 344 female rats. The AHP amplitude was enhanced in aged (22-24 mo) compared with young (5-8 mo) rats and direct application of EB (100 pM) reduced the AHP in aged rats. The age-related difference was due, in part, to the increased AHP amplitude of aged animals, since an EB-mediated decrease in the AHP could be observed in young rats when the extracellular Ca(2+) was elevated to increase the AHP amplitude. In aged rats, bath application of EB occluded the ability of the L-channel blocker, nifedipine (10 microM), to attenuate the AHP. The results support a role for EB in modifying hippocampal Ca(2+)-dependent processes in a manner diametrically opposite that observed during aging, possibly through L-channel inhibition.

Aging↗

Calcium dysregulation in the aging brain.

The idea that age-related cognitive decline is associated with disruption of calcium (Ca2+) homeostasis has been investigated over the past two decades. Much of this work has focused on the hippocampus because hippocampal-dependent memory is age sensitive. It is now well established that Ca(2+)-dependent processes such as susceptibility to neurotoxicity, the afterhyperpolarization amplitude, induction of synaptic plasticity, and long-term potentiation and long-term depression are altered with age. Recent work has identified changes in Ca2+ signaling pathways that may underlie the development of these biological markers of aging. This review considers recent findings concerning interactions between the various Ca(2+)-dependent processes, with special emphasis on the role of altered Ca2+ regulation and disruption of Ca2+ signaling pathways in mediating the expression of biological and behavioral markers of brain aging.

Aging↗

Sacrococcygeal teratoma: a case report.

A 23-year old second gravida presented with 8 1/2 months of amenorrhoea. The fundal height corresponded with 36 weeks of pregnancy with a single live foetus. Ultrasonography revealed a live foetus and a cystic mass over lower sacral region. Emergency caesarean section was performed and the baby was delivered with intact sacrococcygeal teratoma. The histopathological examination confirmed the diagnosis of sacrococcygeal teratoma with mature neural elements. The baby had died on day 10 and the postpartum period of the mother was uneventful.

Adult↗

Synthesis and anticonvulsant activity of 1-acetyl-5-arylidenyl-3-(2'-oxo/thiobarbiturinyl)-2-pyrazolines.

1-(2'-Oxo/thiobarbiturinyl)-3-arylidenylchalcones (3-14) were synthesized by the condensation of different aromatic aldehydes with 5-acetyl-2-oxo/thiobarbituric acid (1 resp. 2) and various 1-acetyl-5-arylidenyl-3-(2'-oxo/thiobarbiturinyl)-2-pyrazolines (15-26) were synthesized by cyclisation of compounds 3-14 with hydrazine hydrate. The newly synthesized compounds showed anticonvulsant activity ranging from 40% to 90%. Compound 23 showed the maximum activity being more potent than the reference drug 1-acetyl-5-(P-methoxyphenyl)-3-(2'-thiobarbiturinyl)-2-pyrazoline.

Animals↗

Ocimum sanctum aqueous leaf extract provides protection against mercury induced toxicity in Swiss albino mice.

HgCl2 (5.0 mg/kg body weight) induced toxicity led to significant elevation of lipid peroxidation (LPO) level but decline in the glutathione content in liver of Swiss albino mice. In serum of HgCl2 treated mice there was significant elevation in serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activities but significant decline in the alkaline phosphatase activity. Animals treated with O. sanctum extract (10 mg/kg body weight, po) before and after mercury intoxication showed a significant decrease in LPO level, SGOT and SGPT activities and increase in serum alkaline phosphatase activity and glutathione (GSH) content. Ocimum treatment alone did not alter SGOT, SGPT and alkaline phosphatase activities but significantly enhanced reduced glutathione. The results suggest that oral administration of Ocimum extract provides protection against HgCl2 induced toxicity in Swiss albino mice.

Administration, Oral↗

Mentha piperita (Linn) leaf extract provides protection against radiation induced alterations in intestinal mucosa of Swiss albino mice.

Intestinal protection in mice against radiation injury by M. piperita (1 g/kg body weight/day) was studied from day 1 to day 20 after whole body gamma irradiation (8 Gy). Villus height, goblet cells/villus section, total cells, mitotic cells and dead cells/crypt section in the jejunum are good parameters for the assessment of radiation damage. There was significant decrease in the villus height, number of total cells and mitotic cells/crypt section, whereas goblet cells and dead cells showed significant increase after irradiation. Mentha pretreatment resulted in a significant increase in villus height, total cells and mitotic cells, whereas goblet cells and dead cells showed a significant decrease from respective irradiated controls at each autopsy day. The results suggest that Mentha pretreatment provides protection against radiation induced alterations in intestinal mucosa of Swiss albino mice.

Animals↗

A Simple Solution to the Age Old Problem of Regioselective Functionalization of Guanine: First Practical Synthesis of Acyclic N(9)- and/or N(7)-Guanine Nucleosides Starting from N(2),N(9)-Diacetylguanine.

Regioselective alkylation of guanine, a long-lasting challenge, has been overcome by understanding the role of acids as catalyst in the coupling reaction of DAG (10) with OBDDA (11). The acid-catalyzed and noncatalyzed reactions of 10 with OBDDA which mainly give N(7) and N(9) isomers, respectively, appear to follow different mechanisms. The practical utility of the noncatalyzed reaction, which gives almost quantitative yields of N(9) derivatives, is demonstrated by synthesizing acylovir/gancyclovir in high yields.

Journal Article↗

Conjugation of penicillin acylase with the reactive copolymer of N-isopropylacrylamide: a step toward a thermosensitive industrial biocatalyst.

Conjugation of penicillin acylase (PA) to poly-N-isopropylacrylamide (polyNIPAM) was studied as a way to prepare a thermosensitive biocatalyst for industrial applications to antibiotic synthesis. Condensation of PA with the copolymer of NIPAM containing active ester groups resulted in higher coupling yields of the enzyme (37%) compared to its chemical modification and copolymerization with the monomer (9% coupling yield) at the same NIPAM:enzyme weight ratio of ca. 35. A 10-fold increase of the enzyme loading on the copolymer resulted in 24% coupling yield and increased by 4-fold the specific PA activity of the conjugate. Two molecular forms of the conjugate were found by gel filtration on Sepharose CL 4B: the lower molecular weight fraction of ca. 10(6) and, presumably, cross-linked protein-polymer aggregates of MW > 10(7). Michaelis constant for 5-nitro-3-phenylacetamidobenzoic acid hydrolysis by the PA conjugate (20 microM) was found to be slightly higher than that of the free enzyme (12 microM), and evaluation of V(max) testifies to the high catalytic efficiency of the conjugated enzyme. PolyNIPAM-cross-linked PA retained its capacity to synthesize cephalexin from d-phenylglycin amide and 7-aminodeacetoxycephalosporanic acid. The synthesis-hydrolysis ratios of free and polyNIPAM-cross-linked enzyme in cephalexin synthesis were 7.46 and 7.49, respectively. Thus, diffusional limitation, which is a problem in the industrial production of beta-lactam antibiotics, can be successfully eliminated by cross-linking penicillin acylase to a smart polymer (i.e., polyNIPAM).

Acrylic Resins↗

Effects of monocrotaline on endothelial nitric oxide synthase expression and sulfhydryl levels in rat lungs.

The nitric oxide-cyclic guanosine monophosphate signal-transduction mechanism plays a key role in the regulation of vascular tone and structure. Monocrotaline-induced pulmonary hypertension is associated with low bioavailability of nitric oxide. To characterize the mechanism(s) involved in this dysfunction, rats received a single subcutaneous injection of monocrotaline, normal saline (control), or monocrotaline plus daily L-arginine, a precursor of nitric oxide, in drinking water. Pulmonary artery pressure and right ventricular hypertrophy were assessed 2 weeks later. In addition, the authors evaluated the expression of endothelial nitric oxide synthase messenger RNA, endothelial nitric oxide synthase protein, cyclic guanosine monophosphate, and sulfhydryl levels in the lungs. Sulfhydryls are needed for the dynamic modulation of soluble guanylate cyclase by nitric oxide, which results in cyclic guanosine monophosphate formation. L-arginine treatment did not attenuate monocrotaline-induced pulmonary hypertension or right ventricular hypertrophy. Monocrotaline did not alter the expression of endothelial nitric oxide synthase messenger RNA or endothelial nitric oxide synthase protein in the lungs. Protein-bound sulfhydryls (28 +/- 5 vs. 75 +/- 16 pmol/microg protein) and cyclic guanosine monophosphate (0.63 +/- 0.05 vs. 1.06 +/- 0.017 pmol/microg protein) levels in the monocrotaline group were significantly low compared with controls. The low sulfhydryl levels, an indicator of oxidant stress, may account for the impaired availability of bioactive nitric oxide and low cyclic guanosine monophosphate levels. These results suggest that oxidative stress may, in part, contribute to the pathogenesis of pulmonary hypertension in the monocrotaline model.

Animals↗

Surgical management of complicated hydatid cysts of the liver.

AIMS: To review the clinical presentation and surgical management of complicated hydatid cysts of the liver. METHODS: Forty-three patients with hydatid disease of the liver were managed surgically between 1991 and 1998. There were 14 men and 29 women with a median age of 34 years. An abdominal ultrasound, computed tomography and serology established diagnosis. Preoperative endoscopic retrograde cholangiography was performed in patients with associated jaundice and high suspicion of intrabiliary rupture. Eleven (26%) patients had complicated cysts and formed the basis for our study. RESULTS: Infection (n = 5, 11%) and intrabiliary rupture (n = 4, 9%) were the common complications. Intrathoracic rupture and intraperitoneal rupture were encountered in one patient each. All patients with infected cysts presented with pain and fever (n = 5, 100%) while those with intrabiliary rupture had jaundice (n = 4, 100%), pain and fever (n = 3, 75%). Surgical procedures performed in complicated cysts were-infection: omentoplasty (n = 2) and external drainage (n = 3); intrabiliary rupture: omentoplasty (n = 2) and internal drainage (n = 2). Patient with intrathoracic and intraperitoneal rupture underwent external drainage. There was no mortality. Postoperative morbidity was encountered in 14 patients and was more in complicated cysts (n = 6/11; 55%) compared to uncomplicated cysts (n = 8/32; 25%). CONCLUSION: Hydatid disease in not an uncommon problem. Around a fourth of patients, present with complications such as infection or intrabiliary rupture. The site, size, number of cysts and presence of complications govern the choice of surgical procedure. Complicated cysts can be successfully managed surgically with good long-term results.

Adult↗