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Biomedical subjects

S Batra

Publications and source records attributed to S Batra.

At least 55 records · Page 3Linked to original sources
PubMed2000

Alterations in antioxidant status during neonatal sepsis.

Septicaemia is a major threat to survival during the early stages of life. There are several reports that suggest that reactive oxygen species (ROs) play a role in a wide variety of diseases. We estimated the activity of xanthine oxidase (XO), malondialdehyde (MDA) content, creatine phosphokinase (CPK) activity, activities of key enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and peroxidase (PO), and non-enzymatic antioxidants, viz. uric acid (UA) and albumin (ALB), in 30 neonates with sepsis and 20 age-matched controls. The babies were categorized as preterm/term, early onset/late onset, and shock/without shock, as per clinical and laboratory investigations. The study was carried out to evaluate the status of antioxidant enzymes and non-enzymatic antioxidants with a view to suggesting the introduction of antioxidant therapy in neonatal sepsis. The activities of serum XO, CPK, SOD and GPx, and the content of MDA were found to be significantly elevated in the neonates with sepsis when compared with controls. Conversely, the activity of PO and the levels of UA and ALB were decreased. The septic, full-term neonates registered significantly higher CPK activity (70%) than the preterm septic neonates. However, infants with late-onset and shock sepsis had a significant decrease in CPK activity (p < 0.05) compared with their corresponding sub-groups. Likewise, UA levels were found to be 28% depressed (p < 0.05) in the babies with late-onset sepsis and 51% increased (p < 0.001) in babies with shock compared with their respective sub-groups. Neonates with septic shock also registered a significant elevation in GPx activity (28%) compared with those without shock. This study suggests increased production of ROs in neonates with sepsis, as evidenced by the positive regulation of XO, SOD and GPx activity. The elevation of antioxidant enzymes, however, was not so effective as to protect from cellular damage and thereby result in higher MDA production. It is evident that antioxidant therapy might be useful in the management of neonates with sepsis but further detailed clinico-biochemical investigations are required to define effective antioxidant therapy.

Antioxidants↗
PubMed2000

Evaluation of free radical status in CSF in childhood meningitis.

The study was undertaken to investigate the possible role of free radicals and antioxidants in childhood meningitis. Sixty children suffering from acute bacterial meningitis (ABM) or tuberculous meningitis (TBM) according to their clinical and laboratory findings were enrolled in the study. The production of superoxide anions (O2.-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) and the activities of xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were monitored in the study groups and findings compared with those in 20 age-matched controls. Children with ABM and TBM who died registered significant increases in the production of O2.- and MDA and in the activities of SOD and CPK compared with survivors. The rate of production of oxidants and MDA and the activities of XO, SOD and CPK were of a much higher magnitude in deceased ABM and in ABM survivors than in fatal TBM and survivors, respectively. The abnormalities in most of the biochemical parameters investigated were more marked in the children with ABM than in TBM and controls (p < 0.001). Increased MDA production and creatine phosphokinase (CPK) activity of different magnitudes in the two study groups suggest varying degrees of tissue damage. The alterations observed in 20 children who died (14 from ABM, 6 from TBM) revealed elevated levels of oxidants, antioxidants and toxicity markers, particularly in ABM patients, which suggests the possibility that natural or synthetic antioxidants might prevent disease progression and tissue damage in childhood meningitis.

Antioxidants↗
PubMed2000

Source of calcium for contractile responses of large and small human intramyometrial arteries.

The role of calcium (Ca(2+)) released from intracellular stores and the entry of extracellular Ca(2+) for vasopressin (AVP)-induced responses in large and small, human, intramyometrial arteries was investigated. There was no statistical difference as revealed by pD(2) values (-log EC(50)), in the sensitivity of large and small vessels to AVP. Nimodipine caused an inhibition of contractions induced by low concentrations (10(-10) mol/l) of AVP in both types of vessels but, at higher concentration (>10(-10) mol/l), whereas responses in small arteries were diminished, in large arteries they remained unchanged. In Ca(2+)-free solution, responses of large and small arteries to potassium and to 10(-10) mol/l AVP were abolished. With 10(-6) mol/l AVP, response in small arteries was completely inhibited, whereas in large arteries it was reduced by approximately 50%. Additional experiments were done on large arteries. Thapsigargin (TSG), which causes depletion of internal Ca(2+) stores, caused a significant reduction in responses. Following treatment with TSG, responses to AVP in Ca(2+)-free solution were almost completely inhibited but arteries responded again when incubated in normal physiological salt solution. The results indicate that in contrast to large arteries, small arteries are highly dependent on extracellular Ca(2+). Response of large arteries showed considerable dependence on Ca(2+) stored internally particularly, for maximum activation.

Adult↗
PubMed2000

Permeability of fetal membranes to calcium and magnesium: possible role in preterm labour.

Calcium (Ca(2+)) and magnesium (Mg(2+)) are co-factors in the synthetic activity of a variety of enzymes and in the secretory process. Both the binding to fetal membranes and the diffusion through the membranes of these two cations could be important factors in the synthesis and/or action of prostaglandins and generation of nitric oxide (NO) which are believed to regulate myometrial activity particularly for the induction of labour. In the present study, the permeability to Ca(2+) and Mg(2+) of chorioamniotic membranes obtained from women who had undergone term or preterm labour was examined. Diffusion of Ca(2+) and Mg(2+) were measured using a system of Plexiglas chambers separated by the mounted fetal membrane. Permeability of Mg(2+) and Ca(2+) through fetal membranes was calculated using non-linear regression analysis. The data show highly significant differences in the diffusion of Ca(2+) and Mg(2+) across fetal membranes between preterm and term labour. Transport coefficient K for Ca(2+) was 0.203 h(-1) and 0. 0223 h(-1) in term and preterm labour respectively. The corresponding values for Mg(2+) were -0.017 h(-1) and 0.051 h(-1) respectively. It is proposed that a considerable reduction in Ca(2+) available to myometrium and placenta would result in down-regulation of nitric oxide synthase (NOS) activity and thereby a reduction in NO production. This together with an effect on intracellular Ca(2+) transport resulting from a reduced availability of Mg(2+) would lead to increased myometrial activity in preterm labour.

Calcium↗
PubMed2000

Nitric oxide synthase in the rabbit uterus and vagina: hormonal regulation and functional significance.

The effects of estrogen (E(2)), progesterone (P(4)), and E(2) and P(4) (E(2)+P(4)) on uterine, vaginal, and cerebellar nitric oxide synthase (NOS) were examined. Additionally, experiments were done to investigate whether NOS-containing nerves were present in the uterus and vagina and the extent to which vaginal smooth muscle response was dependent on nitric oxide (NO). Cytosolic NOS was determined by the formation of [(14)C]citrulline from [(14)C]arginine, and NOS localization was visualized by immunohistochemistry. Vaginal smooth muscle relaxation was induced by electrical field stimulations (EFS). NOS activity in the uterus was markedly down-regulated in all hormone-treated groups. Vaginal NOS activity was nearly 4-fold higher than the uterine NOS activity and was considerably reduced by E(2) or E(2)+P(4) treatment. In contrast to findings in the uterus, P(4) treatment up-regulated vaginal NOS. Hormone treatment had no significant effect on cerebellar NOS. NOS-containing nerves could be demonstrated in the uterus and vagina by immunohistochemistry. Vaginal smooth muscle responded with relaxation after EFS, which was inhibited by N(G)-nitro-L-arginine. A relatively high vaginal NOS, a down-regulation by E(2), an up-regulation by P(4), and NO-dependent response of vaginal smooth muscle suggest a tissue-specific physiological role.

Animals↗
PubMed2000

Assessment of myocardial perfusion by power contrast imaging using a new echo contrast agent.

In a patient with previously documented myocardial infarction, we assessed myocardial perfusion by using power contrast imaging and a newer intravenous echo contrast agent. The images were captured and stored digitally, and various image processing algorithms were used to assess myocardial perfusion. An apical perfusion defect was clearly visualized, and it correlated with radionuclide findings.

Contrast Media↗
PubMed2000

2'-hydroxychalcone inhibits nuclear factor-kappaB and blocks tumor necrosis factor-alpha- and lipopolysaccharide-induced adhesion of neutrophils to human umbilical vein endothelial cells.

Inhibition of expression of cell adhesion molecules (CAM), including intercellular CAM-1 (ICAM-1), vascular CAM-1 (VCAM-1), and E-selectin, has been shown to be important in controlling various inflammatory diseases. The cell adhesion proteins are induced by various inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1, and bacterial lipopolysaccharide. The induction process primarily takes place at the level of transcription, where nuclear factor-kappaB (NF-kappaB) plays a major role. We demonstrate here that 2'-hydroxychalcone inhibits the adhesion of peripheral neutrophils to the endothelial cell monolayers by inhibiting the expression of ICAM-1, VCAM-1, and E-selectin in a concentration-dependent manner. The inhibition by 2'-hydroxychalcone is reversible. 2'-hydroxychalcone inhibits the induction of steady-state transcript levels of ICAM-1, VCAM-1, and E-selectin by tumor necrosis factor-alpha as determined by reverse transcription-polymerase chain reaction, and therefore it may interfere with the transcription of their genes. Because NF-kappaB is a major transcription factor involved in CAM expression, we studied its status in the 2'-hydroxychalcone treated cells. We demonstrate that 2'-hydroxychalcone inhibits the activation of NF-kappaB. These results have implications for using NF-kappaB inhibitors for the treatment of various inflammatory diseases.

Biological Transport↗
PubMed2000

Mitochondrial and microsomal peripheral benzodiazepine receptors in human ovarian cancer xenografts.

To investigate whether the density of peripheral benzodiazepine receptors (PBR) in human ovarian tumors is related to the degree of histological differentiation and possibly elucidate their pathophysiology, PBR were measured in mitochondrial (m) and microsomal (p) fractions isolated from six different human ovarian carcinomas heterotransplanted into nude mice. A specific ligand PK11195 for PBR was employed and the density of binding sites and binding affinity (KD) were computed from Scatchard analysis. The PBR density in m-fractions was 3- to 4-fold higher than in p-fractions from all tumors. PBR density in both m- and p-fractions was highest in mucinous tumors with mid-high degree of differentiation. The density in serous tumor with mid-high differentiation was significantly lower than the mucinous tumor, but higher than the serous tumor with low degree of differentiation (OVCAR-3) in both m- and p-fractions. However, the PBR density in the undifferentiated tumor (IGROV1) was higher than in OVCAR-3. The KD values for PBR were very low ranging from 5.8 to 14.0 nM in all preparations. The KD values for p-fractions were generally lower than m-fractions and highly significant differences were observed in three of the six tumors. These data suggest two separate classes of PBR pertaining to m- and p-fractions and indicate that there is no clear relationship between PBR density and degree of differentiation.

Animals↗
PubMed2000

Free oxygen radicals in acute renal failure.

OBJECTIVE: To assess the levels of free oxygen radicals in acute renal failure and their predictive value in clinical outcome. DESIGN: Prospective. SETTING: Intensive care unit. METHODS: Study was conducted in 50 children (25 with acute renal failure and 25 age and sex matched controls). Blood urea, serum creatinine, serum protein, uric acid and free oxygen radical markers were estimated in both groups. Superoxide dismutase (SOD), glutathione peroxidase(GPx) and lipid peroxide (LPO) were estimated in blood by standard techniques. RESULTS: Hemolytic uremic syndrome (HUS) was a major cause of acute renal failure (52%), rest were due to acute glomerulonephritis (AGN), septicemia and renal venous thrombosis. In the renal failure group 56% of the patients were dialyzed (peritoneal) and the mortality was 28% (7/25). The levels of SOD, GPx and LPO were significantly raised in renal failure group. Higher values of LPO, SOD and GPx were documented in subjects who expired. The most important independent variable for predicting clinical outcome was LPO with a sensitivity of 89.4%, specificity of 93%, positive predictive value of 95%. CONCLUSION: Levels of free oxygen radicals (SOD, LPO and GPx) are raised in acute renal failure and these enzymes can be used as marker of renal injury. LPO levels are highly sensitivity and specific for predicting the clinical outcome

Acute Kidney Injury↗
PubMed2000

CSF interleukin-1 beta, tumor necrosis factor-alpha and free radicals production in relation to clinical outcome in acute bacterial meningitis.

OBJECTIVE: To study the relationship of CSF IL-1 beta and TNF-alpha with free radicals in acute bacterial meningitis (ABM) and to evaluate the clinical outcome in relation to the levels of these cytokines and free radicals in CSF. DESIGN: Prospective with controls. SETTING: Referral unit of a teaching hospital. METHODS: 32 children between 3m-12 yrs of age with proven acute bacterial meningitis comprised the study group. In the control group, 20 children with febrile seizures were included. CSF cytokines- Interleukin Ib and tumour necrosis factor a,free radicals O(2)-, H(2)O(2) and enzymes SOD and CPK were measured in all the children. RESULTS: CSF IL-Ib and TNF-a concentration were markedly elevated in children with ABM (441.5 +/- 216.1 pg/ml, and 1009 +/- 529.1 pg/ml, respectively) as compared to controls (52.67 +/- 6.92 pg/ml, and 86.42 +/- 16.24 pg/ml) (p <0.0001). Free radicals viz., superoxide anion, hydrogen peroxide production and enzymes creatinine phosphokinase and superoxide dismutase were also significantly elevated in ABM as compared to controls. There was direct correlation of CSF cytokines with CSF cytology, protein and free radicals production in ABM. Patients who expired or had neurological sequelae had markedly elevated concentrations of cytokines and free radicals. CONCLUSION: IL-I beta, TNF-alpha and free radicals are significantly elevated in CSF of patients with ABM. The concentration of these cytokines correlated well with free radical production, and with routinely measured CSF parameters and had a direct bearing on outcome of ABM

Acute Disease↗
PubMed1999

Emergency laparoscopic repair of a paraesophageal hernia.

A 63-year-old male with a previously documented paraesophageal hernia presented with acute severe epigastric pain and bloating. He was taken urgently to the operating room for laparoscopic exploration. The hernia sac was reduced with difficulty owing to extensive adhesions and the incarcerated portion of the stomach was mottled and blue. After 10 min of observation the stomach began to resume a normal appearance. The anterior crura were approximated and an anterior gastropexy was performed. The patient was discharged on the 3rd postoperative day and has been asymptomatic since. Paraesophageal hernias with evidence of impending gastric necrosis can be approached laparoscopically as long as basic principles are observed.

Emergency Treatment↗
PubMed1999

Downregulation by estrogen of nitric oxide synthase activity in the female rabbit lower urinary tract.

OBJECTIVES: Because female urinary tract tissues are considered to be targets for estrogen, and because nitric oxide (NO) is known to participate in the nerve-induced relaxation in the lower urinary tract, the effect of estrogen on nitric oxide synthase (NOS) in the upper and lower urinary tracts was examined. METHODS: Ovariectomized rabbits were treated with polyestradiol phosphate, and NOS in both cytosolic and particulate fractions from kidney, urinary pelvis, ureter, urinary bladder, trigonum, and urethra was characterized. NOS activity was measured by the formation of [14C]-L-citrulline from [14C]-L-arginine. RESULTS: NOS was considerably higher in cytosolic than in particulate fractions from all urinary tracts, and activity in both fractions was highly calcium dependent. NOS activity was much lower (fourfold to eightfold) in the kidney and pelvis than in the ureter. Estrogen treatment caused no change in NOS in either fraction from upper urinary tract tissues. In the lower urinary tract, NOS was slightly higher in the bladder and trigonum than in the urethra, and activities were comparable to NOS in the ureter. In contrast to the upper urinary tract, estrogen treatment led to a significant reduction of cytosolic NOS in the bladder, trigonum, and urethra. Estrogen, however, caused no significant change in the particulate NOS. CONCLUSIONS: Downregulation by estrogen in cytosolic NOS in the tissue of the lower urinary tract is consistent with the presence of estrogen receptors and suggests a physiologic significance.

Animals↗
PubMed1999

Activation of phospholipase C and protein kinase C is required for expression of anthrax lethal toxin cytotoxicity in J774A.1 cells.

Anthrax lethal toxin (LT) comprises two proteins: the protective antigen (PA) and the lethal factor (LF). The LT is cytotoxic to macrophage-like cell line J774A.1. Pre-treatment of these cells with neomycin, a phospholipase C inhibitor, protected them against anthrax LT cytotoxicity. Protection obtained with neomycin indicated that LT stimulates phospholipase C in these cells. It was found that levels of inositol 1,4,5-triphosphate (IP3) dramatically increased in toxin-treated cells. The rise in IP3 levels was proportional to the dose of LF that was allowed to bind to receptor-bound PA. By using protein kinase C (PKC) inhibitors, we found that the activation of PKC is required for mediating anthrax LT cytotoxicity. Activation of phospholipase C or PKC is not required for the binding of PA to the cell surface receptors or for the uptake or internalisation of the toxin. In this study, we demonstrate that the IP3 signalling cascade is initiated by anthrax lethal toxin in J774A.1 cells. The second messengers generated during the cascade aid LF in mediating lethality only after its translocation into the cytosol.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro.

Our previous studies in the hamster pancreatic cancer model have indicated that pancreatic ductal adenocarcinomas derive not only from ductal/ductular cells but also from islets. To verify the presence of carcinogen-responsive cells within islets, we tested the effect of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) on recently established continuous hamster pancreatic islet culture. Isolated pure pancreatic islets of hamsters were treated in vitro with BOP at a concentration of 0.25 mM three times a week for 19 weeks. Each treatment week was designed as a stage. The growth of these cells, designated KL5B, was compared with untreated cultured islets, designated KL5N. As in our previous study, between 14 and 21 days of culture, exocrine and intermediary cells developed within both KL5N and KL5B islets, which were then replaced by undifferentiated cells. No differences were found in the growth patterns of KL5N and KL5B until stage 4, when KL5B cells showed accelerated cell growth and cell pleomorphism, which increased gradually at later stages of treatment. Anchorage-independent and in vivo growth did not appear until stage 19. Mutation of c-Ki-ras at codon 12 (GGT-->GAT) was detected in KL5B cells but not in KL5N cells. In vivo KL5B cells formed anaplastic invasive cancer with areas of glandular formation, overexpressed TGF-alpha and EGFR, expressed cytokeratin, vimentin, laminin and alpha-1 antitrypsin and reacted strongly with L-phytohemagglutinin and tomato lectin. Some cells within islets are responsive to the carcinogenic effects of BOP. Whether these cells represent islet cell precursors (stem cells) or malignant transdifferentiated islet cells remains to be seen.

Adenoma, Islet Cell↗
PubMed1999

Status of antioxidants and other biochemical abnormalities in children with dengue fever.

During an outbreak of dengue fever in 1996, 66 children between 45 days and 12 years of age with dengue fever and 25 healthy controls were studied for antioxidants and other biochemical abnormalities. As per World Health Organization (WHO) criteria, 14 children were classified as having classical dengue (DEN), 42 with dengue haemorrhagic fever (DHF), and 10 (including three who died) as having dengue shock syndrome (DSS). Superoxide dismutase (SOD), glutathione peroxidase (GPX), and albumin (ALB), the three main antioxidants studied, were found to be abnormal in 96, 94, and 40 per cent of the cases respectively. The levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CPK), total protein (TP), total cholesterol (CHO), and triglycerides (TGL) were abnormal in 79, 50, 30, 93, and 67 per cent of the cases respectively. Among the different groups of dengue the abnormalities were more marked in children with DSS than in those with DEN and DHF, especially with respect to ALB, TP, TGL, AST, ALT, and CPK (p < 0.005). This preliminary report of dengue confirms the assumption of free radical generation and alteration in antioxidant status during acute illness. However, to understand their complex interaction in disease progression and therapeutic utility, further studies are required.

Antioxidants↗
PubMed1999

Effect of acute normovolemic hemodilution on distribution of blood flow and tissue oxygenation in dog skeletal muscle.

Acute normovolemic hemodilution (ANH) is efficient in reducing allogenic blood transfusion needs during elective surgery. Tissue oxygenation is maintained by increased cardiac output and oxygen extraction and, presumably, a more homogeneous tissue perfusion. The aim of this study was to investigate blood flow distribution and oxygenation of skeletal muscle. ANH from hematocrit of 36 +/- 3 to 20 +/- 1% was performed in 22 splenectomized, anesthetized beagles (17 analyzed) ventilated with room air. Normovolemia was confirmed by measurement of blood volume. Distribution of perfusion within skeletal muscle was determined by using radioactive microspheres. Tissue oxygen partial pressure was assessed with a polarographic platinum surface electrode. Cardiac index (3.69 +/- 0.79 vs. 4.79 +/- 0.73 l. min-1. m-2) and muscle perfusion (4.07 +/- 0.44 vs. 5.18 +/- 0.36 ml. 100 g-1. min-1) were increased at hematocrit of 20%. Oxygen delivery to skeletal muscle was reduced to 74% of baseline values (0.64 +/- 0.06 vs. 0.48 +/- 0.03 ml O2. 100 g-1. min-1). Nevertheless, tissue PO2 was preserved (27.4 +/- 1.3 vs. 29.9 +/- 1. 4 Torr). Heterogeneity of muscle perfusion (relative dispersion) was reduced after ANH (20.0 +/- 2.2 vs. 13.9 +/- 1.5%). We conclude that a more homogeneous distribution of perfusion is one mechanism for the preservation of tissue oxygenation after moderate ANH, despite reduced oxygen delivery.

Animals↗
PubMed1999

Status of lipid peroxidation and antioxidant enzymes in hypoxic ischemic encephalopathy.

OBJECTIVE: To compare the activities of key antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase] and the level of malonyl dialdehyde (MDA) in neonates with hypoxic ischemic encephalopathy (HIE) and controls. DESIGN: Prospective cross sectional study. SETTING: Tertiary care level II neonatal unit of teaching hospital. METHODS: Fifteen term new borns with HIE were registered for the study whereas normal term appropriate for gestational age babies were enrolled as controls. Clinical features were recorded. Activities of SOD, GPx, catalase and the content of MDA were estimated at 24 hours of age. The results obtained were statistically analyzed. RESULTS: Activities of SOD and Catalase and the level of MDA were significantly higher in cases as compared to the controls. There was however no significant alternation in the activity of GPx levels in both the groups. CONCLUSION: The increased activities of antioxidant enzymes are unable to counteract the excessively generated oxidants in vivo, as is evident from the increased MDA levels. Hence, oxygen free radicals may play a significant role in the pathogenesis of HIE.

Case-Control Studies↗