Evaluation of a new posterior subgluteus approach to sciatic nerve.
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Biomedical subjects
Publications and source records attributed to Ashok Kumar.
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Two cases of haematocolpos in adolescent girls due to imperforate hymen are reported. Both of them presented with lower abdominal pain and urinary retention. Hymenotomy was performed in both the cases. The condition is discussed with brief review of literature.
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.
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.
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.
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.
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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.
The capture of human acute myeloid leukemia KG-1 cells expressing the CD34 surface antigen and the fractionation of human blood lymphocytes were evaluated on polyvinyl alcohol (PVA)-cryogel beads and dimethyl acrylamide (DMAAm) monolithic cryogel with immobilized protein A. The affinity ligand (protein A) was chemically coupled to the reactive PVA-cryogel beads and epoxy-derivatized monolithic cryogels through different immobilization techniques and the binding efficiency of the cell surface receptors specific antibody-labeled cells to the gels/beads was determined. The binding of cells to monolithic cryogel was higher (90-95%) compared with cryogel beads (76%). B-lymphocytes, which bound to the protein A-cryogel beads, were separated from T-lymphocytes with yields for the two cell types 74 and 85%, respectively. About 91% of the bound B-cells could be recovered without significantly impairing their viability. Our results show differences in the percentage of cell-binding to the immunosorbents caused by ligand density, flow shear forces and bond strength between the cells and the affinity surface once distinct chemical coupling of protein A, size of beads, sequence of antibody binding to protein A adsorbents, morphology and geometry of surface matrices were compared.
An integrated product recovery system was developed to separate urokinase from the cell culture broth of human kidney cells HT1080. Supermacroporous monolithic cryogels provided ideal matrices with respect to surface and flow properties for use as cell culture scaffold as well as for affinity chromatographic capture step of the enzyme in the integrated system. The urokinase was produced continuously in the reactor running for 4 weeks with continuous circulation of 500 ml of culture medium. The enzyme activity in the culture medium reached to 280 Plough units (PU)/mg protein. Cu(II)-iminodiacetic acid (IDA)-polyacrylamide (pAAm) cryogel column was used to capture urokinase by integrating with the gelatin-coupled pAAm-cryogel bioreactor for HT1080 cell culture. After removing the urokinase capture column from the integrated system the bound protein was eluted. The metal affinity capture step gave 4.5-fold purification of the enzyme thus achieving a specific activity of 1300 PU/mg protein. The enzyme eluate from Cu(II)-IDA-pAAm cryogel capture column was further purified on benzamidine-Sepharose affinity column. This step finally led to a homogeneous preparation of different forms of urokinase in two different elution peaks with a best urokinase activity of 13 550 PU/mg of protein. As compared to initial activity in the cell culture broth, about 26.2- and 48.4-fold increase in specific activity was achieved with enzyme yields corresponding to 32% and 35% in two different peak fractions, respectively. Native electrophoresis and SDS-PAGE showed multiple protein bands corresponding to different forms of the urokinase, which were confirmed by Western blotting and zymography.
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).
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.
1. Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke and renal failure. The incidence of hypertension is 25-30% in the adult Caucasian population and complications due to hypertension are even greater in African Americans. 2. The renin-angiotensin system plays an important role in the regulation of blood pressure and previous studies have suggested that angiotensinogen (AGT) gene locus is linked with human essential hypertension. Earlier studies suggested that a single nucleotide polymorphism (SNP) that converts methionine to threonine at amino acid 235 is associated with hypertension in the Caucasian population. However, this SNP is not associated with hypertension in African American and Chinese populations. 3. We have found an A/G polymorphism at -217 of the human AGT gene promoter and have shown that the frequency of allele A at -217 is significantly increased in the genomic DNA of African American hypertensive patients. 4. We have also shown that: (i) reporter constructs containing the AGT gene promoter with nucleoside A at -217 have increased promoter activity on transient transfection; and (ii) the CCAAT box enhancer binding protein (C/EBP) family of transcription factors and glucocorticoid receptor (GR) bind preferentially to this region of the promoter when nucleoside A is present at -217. In addition, variant -217A is always present with variants -532T, -793A and -1074T in the human AGT gene promoter. 5. These data suggest that the AGT haplotype containing -217A, -532T, -793A and -1074T may be involved in increased transcription of this gene and may play a role in human hypertension.
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.
OBJECTIVES: To analyze the morphological changes in bile ducts following endobiliary stent insertion, and consequent technical problems encountered at surgery. METHODS: Data on bile duct morphology--gross (luminal diameter and wall thickness) and microscopic (histological changes in bile duct wall graded semiquantitatively)--and operative parameters related to bile duct dissection (grade of difficulty in dissection) were collected prospectively in 31 consecutive patients undergoing pancreatico-duodenectomy. These data were compared between patients who had undergone preoperative endoscopic biliary stent placement (n=17) and those who had not (n=14). RESULTS: Mean duration of stenting before surgery was 34 (range 10-120) days. Stented ducts were significantly narrower (luminal diameter 9 [7-12] mm vs. 17.5 [8-23] mm; p=0.0001) and had thicker walls (2.3 [1.3-3.5] mm vs. 1.85 [0.8-2.2] mm; p=0.004) compared to non-stented ones. On microscopy, stented ducts had advanced grades of submucosal gland hypertrophy, fibrosis and inflammatory cell infiltrate. Difficulty in bile duct dissection was encountered more often in patients who had been stented than in those without stents, though the difference was not statistically significant. CONCLUSION: Endobiliary stent placement results in significant morphological and fibroproliferative inflammatory changes in bile ducts, making dissection difficult.
The antiphospholipid syndrome encompasses a wide spectrum of presentations cutting across all subspecialties of medicine. It is characterized by recurrent thrombotic events involving both the arterial and venous systems. Large arteries and veins as well as the microcirculation are involved. Recurrent strokes, myocardial infarction, pulmonary embolism, gangrene of the digits, etc. cause much morbidity and mortality in affected patients. It is recognized as an important cause of recurrent pregnancy loss. The risk in pregnancy extends to a propensity towards pre-eclampsia, abruptio placentae and intrauterine growth retardation. It often manifests as asymptomatic thrombocytopenia and sometimes as a life-threatening form called catastrophic anti-phospholipid syndrome. The management of thrombotic events rests on high grade anticoagulation (INR 3-4) as lower values of INR than this often fail to prevent recurrence. Aspirin is generally added in case of arterial thrombosis. A combination of heparin and aspirin at least in the first trimester and sometimes throughout pregnancy is used to prevent foetal loss.
Interaction of CD44, an adhesion molecule, with its extracellular matrix ligand, hyaluronan (HA), has been suggested to play a critical role in a number of biological manifestations, including cell migration, tumorigenesis, metastasis, and regulation of immune responses. CD44 comprises a large family of transmembrane glycoproteins that exhibit extensive molecular heterogeneity. This heterogeneity in size is generated by alternative RNA splicing of variable exons as well as by post-translational modifications. Most cell types express CD44 but do not bind HA. The biological functions of CD44, including the regulation of lymphocyte recruitment to the sites of inflammation, have been attributed to the generation of a functionally active, HA-adhesive phenotype. The molecular mechanisms underlying the regulation of CD44 expression and the generation of a functionally active HA-binding phenotype are not well understood. Recently, CD44-HA interactions have been reported to play a critical role in a number of autoimmune diseases in humans and experimental animal models. Initial studies have taken advantage of anti-CD44 antibodies which specifically block CD44-HA interactions. Administration of these antibodies in several experimental murine models of autoimmune diseases resulted in alleviation of inflammatory reactions. In addition, the generation of CD44-deficient animals has facilitated our understanding of the involvement of CD44 in inflammation and autoimmune diseases. This review will focus on the recent advances in the molecular mechanisms regulating CD44 expression, ligand binding, as well as the contribution of CD44 to the development of inflammation and autoimmune disorders.
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