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Biomedical subjects

S Chandra

Publications and source records attributed to S Chandra.

At least 19 recordsLinked to original sources

Risk factors and clinical outcomes of pulmonary interstitial emphysema in extremely low birth weight infants.

OBJECTIVE: We studied the ante- and postnatal risk factors and clinical outcomes associated with pulmonary interstitial emphysema (PIE) in extremely low birth weight infants (ELBW, <1000 g at birth) in the present era of tocolytics, antenatal steroid and postnatal surfactant administration. STUDY DESIGN: This was a retrospective case-controlled study of all ELBW admitted consecutively during a designated study-period in a level III nursery. Data were analyzed by performing univariate and multivariate analysis as applicable. RESULTS: Infants with PIE had lower 1 and 5 min Apgar scores (P=0.04 and 0.003 respectively), increased surfactant utilization (P=0.004), higher maximum inspired oxygen concentration (P=0.04) and mean airway pressure administration (P=0.02) during the first week of life, and increased neonatal mortality (P=0.01). They received higher antenatal doses of magnesium sulfate (MgSO(4)) (P=0.02). 56% of infants with PIE were exposed to more than 10 g of MgSO(4) (Mg10), compared to 15% in non-PIE group (P=0.01). The multivariate logistic regression analysis including significant co-variates revealed an independent association between Mg10 and PIE (P=0.01, Odds ratio 19.8, 95% CI 1.5-263). CONCLUSION: Pulmonary interstitial emphysema is associated with increased mortality in ELBW infants. Mg10 is an independent risk factor for PIE in this population.

Apgar Score↗

In vivo cytogenetic effects of a commercially formulated mixture of cypermethrin and quinalphos in mice.

In vivo cytogenetic effects of commercially formulated cypermethrin (CYP, synthetic pyrethroid insecticide) and/or quinalphos (QUI, organophosphate insecticide), generally used in combination, were examined through chromosomal aberrations (CA) and micronucleus test (MT) in mice. Male mice were orally gavaged to a single dose of CYP/QUI commercial mixture (22, 44 or 67 mg/kg b.wt.) for 24h (CA) or 48 h (MT). Based on the concentrations of active ingredients of CYP and QUI present in the test doses of CYP/QUI mixture, mice were orally exposed to 0.66, 1.32 and 2 mg/kg of CYP or 4.4, 8.8 and 13.4 mg/kg of QUI. For reference, a group of five mice was intraperitoneally administered to cyclophosphamide (20 or 50 mg/kg) or orally gavaged to peanut oil for vehicle control. Exposure of CYP/QUI mixture inhibited the mitotic index (MI) and induced CA in a dose-dependent manner at 24 h; however, significant (p<0.01 or 0.001) frequencies of CA were observed at 44 mg/kg onwards, whereas inhibition of MI at 67 mg/kg. Independent exposure of QUI at 8.8 mg/kg onwards also significantly (p<0.01 or 0.001) inhibited MI and induced CA, whereas CYP at 2 mg/kg (highest concentration in CYP/QUI mixture) inhibited MI significantly but failed to induce CA. Chromatid breaks and fragments found to be frequent aberrations in all the test groups. Treatment of CYP/QUI mixture also induced micronucleus formation dose-dependently at 48 h, yet statistically significant (p<0.001) frequencies of micronucleated polychromatic erythrocytes (MNPCE) were observed at 44 mg/kg onwards. QUI (8.8 and 13.4 mg/kg) alone also induced significant frequencies of MNPCE, whereas frequencies of MNPCE observed with the CYP even at 2 mg/kg were comparable to that of vehicle control. Present findings indicate the genotoxicity potential of CYP/QUI mixture and suggest that the simultaneous presence of the toxic doses of CYP and QUI can lead to synergistic genotoxicity in mice and may pose mutagenic risk in human beings.

Administration, Oral↗

Antipyretic and analgesic activities of Caesalpinia bonducella seed kernel extract.

Ethanolic extract (70%) of Caesalpinia bonducella seed kernel has been subjected for its antipyretic and antinociceptive activities in adult albino rats or mice of either sex at 30, 100 and 300 mg/kg orally. The extract demonstrated marked antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract had significant central analgesic activity in hot plate and tail flick methods. It also exhibited marked peripheral analgesic effect in both acetic acid-induced writhing test in mice and Randall-Selitto assay in rats. It also significantly inhibited the formalin-induced hind paw licking in mice. In conclusion, the present study suggests that the ethanolic extract of Caesalpinia bonducella seed kernel possesses potent antipyretic and antinociceptive activities and thus, validates its use in the treatment of pain and pyretic disorders.

Acetic Acid↗

The effect of vaginal pH on labor induction with vaginal misoprostol.

OBJECTIVE: To estimate the association of vaginal pH on the induction to vaginal delivery interval in labor induction with vaginal misoprostol. METHODS: Women presenting at term with intact membranes for labor induction were recruited. The pH of the vagina was measured during a digital examination of the cervix to determine the Bishop Score. Labor was induced with 25 microg of vaginal misoprostol placed every 6 h until spontaneous rupture of membranes or active labor occurred. The primary outcome was the induction to vaginal delivery interval in the lower pH (< 5) versus higher pH (> or = 5) group. Secondary outcomes assessed maternal and neonatal morbidities. Sample size calculated a priori estimated 120 subjects were required for a power of 95% and a 2-tailed a of 0.05. RESULTS: 120 women met inclusion criteria and had available pH data. There was no difference in the induction to vaginal delivery interval in the lower pH (1455 min) versus higher pH group (1295 minutes, Mean difference 160 [- 147,468] P = .30). No difference was observed for operative delivery rates or neonatal outcomes. CONCLUSION: The pH of the vagina may not affect the length of the induction to vaginal delivery interval in women undergoing labor induction with vaginal misoprostol. Further research is required to determine factors that may influence the efficacy of vaginal misoprostol when used for labor induction.

Administration, Intravaginal↗

Randomized controlled trial of intrapleural streptokinase in empyema thoracis in children.

AIM: To compare intrapleural streptokinase and placebo in paediatric empyema. METHODS: Children with empyema greater than stage 5 received intrapleural streptokinase (n = 19) or normal saline (n = 21) along with intercostal drainage. Clinical and serial sonographic outcomes were compared. RESULTS: Although there was no difference in clinical and sonographic outcome, none of the children with stage 7 empyema (multi-loculated empyema) who received streptokinase developed pleural thickening 30 d later. CONCLUSION: There is no short-term clinical benefit of intrapleural streptokinase in paediatric empyema; this therapy may be reserved for those with stage 7 empyema to prevent pleural thickening in the long term.

Anti-Bacterial Agents↗

The Ribosomal Database Project (RDP-II): previewing a new autoaligner that allows regular updates and the new prokaryotic taxonomy.

The Ribosomal Database Project-II (RDP-II) pro-vides data, tools and services related to ribosomal RNA sequences to the research community. Through its website (http://rdp.cme.msu.edu), RDP-II offers aligned and annotated rRNA sequence data, analysis services, and phylogenetic inferences (trees) derived from these data. RDP-II release 8.1 contains 16 277 prokaryotic, 5201 eukaryotic, and 1503 mitochondrial small subunit rRNA sequences in aligned and annotated format. The current public beta release of 9.0 debuts a new regularly updated alignment of over 50 000 annotated (eu)bacterial sequences. New analysis services include a sequence search and selection tool (Hierarchy Browser) and a phylogenetic tree building and visualization tool (Phylip Interface). A new interactive tutorial guides users through the basics of rRNA sequence analysis. Other services include probe checking, phylogenetic placement of user sequences, screening of users' sequences for chimeric rRNA sequences, automated alignment, production of similarity matrices, and services to plan and analyze terminal restriction fragment polymorphism (T-RFLP) experiments. The RDP-II email address for questions or comments is rdpstaff@msu.edu.

Animals↗

Antinociceptive and antipyretic activities of Pongamia pinnata leaves.

In the present study, the antinociceptive activity of a 70% ethanol extract of Pongamia pinnata leaves (PLE) was investigated in different models of pain in mice and rats. Further, PLE was also evaluated for its antipyretic activity in Brewer's yeast-induced pyrexia in rats. Per os (p.o.) administration of the PLE (100-1000 mg/kg) produced significant antinociceptive activity in the hotplate and tail flick (central) as well as in acetic acid writhing and Randall-Selitto (peripheral) nociceptive tests suggesting the involvement of both central and peripheral mechanisms in alleviating the pain response. In addition, PLE also exhibited a significant antipyretic response in Brewer's yeast-induced pyrexia in rats. These results demonstrated that PLE possesses marked antinociceptive as well as antipyretic activities and thus scientifically validated its use in the treatment of pain and pyretic disorders.

Acetic Acid↗

Removal of lindane and malathion from wastewater using bagasse fly ash--a sugar industry waste.

The bagasse fly ash, obtained from the local sugar industry, has been used as inexpensive and effective adsorbent for the removal of lindane and malathion from wastewater. The optimum contact needed to reach equilibrium was found to be 60 min. Maximum removal takes place at pH 6.0. The removal of the pesticides increases with an increase in adsorbent dose and decreases with adsorbent particle size. The optimum adsorbent dose is 5 g/l of particle size 200-250 microm. Removal of the two pesticides was achieved up to 97-98% under optimum conditions. The material exhibits good adsorption capacity and follows both Langmuir and Freundlich models. Thermodynamic parameters also indicate the feasibility of the process. The adsorption was found to be exothermic in nature. At lower concentrations, adsorption is controlled by film diffusion, while at higher concentrations, it is controlled by particle diffusion mechanisms. The adsorbent is a very useful and economic product for the removal of lindane and malathion.

Absorption↗

Spinal intramedullary tuberculoma and abscess: a rare cause of paraparesis.

Five cases of spinal intramedullary tuberculomas (IMT) and one case of spinal intramedullary tuberculous abscess (ITA) are presented. Gd enhanced MRI revealed ring enhancing lesion with central hypodensity, suggesting granulomatous pathology. Surgical excision of the intramedullary lesions was carried out in four cases, while two patients received presumptive anti-tuberculous chemotherapy only. Repeat MRI after completion of anti-tuberculous therapy showed total resolution of the lesion. In other cases following surgical excision, the patients improved significantly. The management of these rare lesions is discussed and the literature reviewed.

Adult↗

Inhibitory role of Syzygium cumini on autacoid-induced inflammation in rats.

The ethanolic extract of Syzygium cumini bark has been reported to possess anti-inflammatory activity in our previous studies. The present study is an attempt to elucidate the anti-inflammatory activity of S. Cumini bark against inflammation induced by individual autacoid insult. Histamine (1 mg/ml), 5-HT (1 mg/ml), bradykinin (0.02 mg/ml) and PGE2 (0.001 mg/ml) were used as inflammogens. One of these agents (0.1 ml) was injected s.c. into the right hind paw of each rat. The ethanolic extract of S. cumini bark was tested at the doses of 100, 300 and 1000 mg/kg, p.o. The results indicated the anti-inflammatory activity of S. cumini bark in histamine, 5-HT and PGE2-induced rat paw oedema. However, there was no such significant inhibition of oedema volume observed in bradykinin-induced rat paw oedema at any dose level. Thus, it is concluded that S. cumini exhibits inhibitory role on inflammatory response to histamine, 5-HT and PGE2.

Animals↗

Quantitative imaging and microlocalization of boron-10 in brain tumors and infiltrating tumor cells by SIMS ion microscopy: relevance to neutron capture therapy.

Boron neutron capture therapy (BNCT) is dependent on the selective accumulation of boron-10 in tumor cells relative to the contiguous normal cells. Ion microscopy was used to evaluate the microdistribution of boron-10 from p-boronophenylalanine (BPA) in the 9L rat gliosarcoma and the F98 rat glioma brain tumor models. Four routes of BPA administration were used: i.p. injection, intracarotid (i.c.) injection [with and without blood-brain barrier disruption (BBB-D)], and continuous timed i.v. infusions. i.p. injection of BPA in the 9L gliosarcoma resulted in a tumor-to-brain (T:Br) boron-10 concentration ratio of 3.7:1 when measured at the tumor-normal brain interface. In the F98 glioma, i.c injection of BPA resulted in a T:Br ratio of 2.9:1, and this increased to 5.4:1 when BBB-D was performed. The increased tumor boron uptake would potentially enhance the therapeutic ratio of BNCT by >25%. At present, ion microscopy is the only technique to provide a direct measurement of the T:Br boron-10 concentration ratio for tumor cells infiltrating normal brain. In the 9L gliosarcoma, this ratio was 2.9:1 after i.p. administration. In the F98 glioma, i.c injection resulted in a ratio of 2.2:1, and this increased to 3.0:1 after BBB-D. Ion microscopy revealed a consistent pattern of boron-10 microdistribution for both rat brain tumor models. The boron-10 concentration in the main tumor mass (MTM) was approximately twice that of the infiltrating tumor cells. One hour after a 2-h i.v. infusion of BPA in rats with the 9L gliosarcoma, tumor boron-10 concentrations were 2.7 times higher than that of infiltrating tumor cells [83 +/- 23 microg/g tissue versus 31 +/- 12 microg/g tissue (mean +/- SD)]. Continuous 3- and 6-h i.v. infusions of BPA in the 9L gliosarcoma resulted in similar high boron-10 concentrations in the MTM. The boron-10 concentration in infiltrating tumor cells was two times lower than the MTM after a 3-h infusion. After 6 h, the boron-10 concentration in infiltrating tumor cells had increased nearly 90% relative to the 2- and 3-h infusions. A 24-h i.v. infusion resulted in similar boron-10 levels between the MTM and the infiltrating tumor cells. Boron concentrations in the normal brain were similar for all four infusion times (approximately 20 microg/g tissue). These results are important for BNCT, because clinical protocols using a 2-h infusion have been performed with the assumption that infiltrating tumor cells contain equivalent amounts of boron-10 as the MTM. The results reported here suggest that this is not the case and that a 6-h or longer infusion of BPA may be necessary to raise boron-10 levels in infiltrating tumor cells to that in the MTM.

Animals↗

Hypertensive end-organ damage and premature mortality are p38 mitogen-activated protein kinase-dependent in a rat model of cardiac hypertrophy and dysfunction.

BACKGROUND: Numerous pathological mediators of cardiac hypertrophy (eg, neurohormones, cytokines, and stretch) have been shown to activate p38 MAPK. The purpose of the present study was to examine p38 MAPK activation and the effects of its long-term inhibition in a model of hypertensive cardiac hypertrophy/dysfunction and end-organ damage. METHODS AND RESULTS: In spontaneously hypertensive stroke-prone (SP) rats receiving a high-salt/high-fat diet (SFD), myocardial p38 MAPK was activated persistently during the development of cardiac hypertrophy and inactivated during decompensation. Long-term oral treatment of SFD-SP rats with a selective p38 MAPK inhibitor (SB239063) significantly enhanced survival over an 18-week period compared with the untreated group (100% versus 50%). Periodic echocardiographic analysis revealed a significant reduction in LV hypertrophy and dysfunction in the SB239063-treatment groups. Little or no difference in blood pressure was noted in the treatment or vehicle groups. Basal and stimulated (lipopolysaccharide) plasma tumor necrosis factor-alpha concentrations were reduced in the SB239063-treatment groups. In vitro vasoreactivity studies demonstrated a significant preservation of endothelium-dependent relaxation in animals treated with the p38 MAPK inhibitor without effects on contraction or NO-mediated vasorelaxation. Proteinuria and the incidence of stroke (53% versus 7%) were also reduced significantly in the SB239063-treated groups. CONCLUSIONS: These results demonstrate a crucial role for p38 MAPK in hypertensive cardiac hypertrophy and end-organ damage. Interrupting its function with a specific p38 MAPK inhibitor halts clinical deterioration.

Animals↗

Dynamic secondary ion mass spectrometry analysis of boron from boron neutron capture therapy drugs in co-cultures: single-cell imaging of two different cell types within the same ion microscopy field of imaging.

A co-culture, cryogenic SIMS methodology is presented for the quantitative analysis of cell type-dependent accumulation of boron delivered by BPA-F and BSH, two clinically approved drugs used in boron neutron capture therapy of cancer. T98G human glioblastoma cells were co-cultured with morphologically different normal LLC-PK1 epithelial cells or GM3348 human skin fibroblasts. Our freeze-fracture method of cryogenic sample preparation successfully fractured the different cell types grown together in co-cultures. Quantitative observations revealed an active uptake of boron from BPA-F in both T98G and LLC-PK1 cells but did not show cell type-dependent differences. Accumulation of BSH in all three cell types examined also did not reveal any cell type-dependent differences in co-cultures. As this method relies on the analysis, within the same field of SIMS imaging, of two different cell types that have been maintained under identical conditions of growth, drug exposure, sample preparation, and instrumental analysis, it provides the most effective approach for comparing cell type-specific differences in boron concentrations. The most effective applications of this method will be realized in testing the selectivity of experimental boronated compounds designed to specifically target tumor cells.

Animals↗

The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases.

Amyloid beta-protein (A beta) is the main constituent of senile plaques in Alzheimer's disease and is derived by proteolysis from the amyloid precursor protein (APP). Generation and secretion of both A beta 40 and A beta 42 isoforms depend largely on internalization of APP and occurs mainly in the endocytic pathway. Evidence has also been presented (Gervais, F. G., Xu, D., Robertson, G. S., Vaillancourt, J. P., Zhu, Y., Huang, J., LeBlanc, A., Smith, D., Rigby, M., Shearman, M. S., Clarke, E. E., Zheng, H., Van der Ploeg, L. H. T., Ruffolo, S. C., Thornberry, N. A., Xanthoudakis, S., Zamboni, R. J., Roy, S., and Nicholson, D. W. (1999) Cell, 97, 395--406) that caspase cleavage of APP at its cytosolic tail affects its processing such that it is redirected to a more amyloidogenic pathway, resulting in enhanced A beta generation. However, caspase cleavage of APP also results in loss of its endocytosis signal (YENP), an event that would predict a decline in internalization and a concomitant decrease, not an increase, in A beta generation. In the present work, we examined whether caspase cleavage of APP is relevant to amyloidogenesis. We found that 1) caspase cleavage of APP results in reduced internalization and, accordingly, a decline in A beta secretion; 2) masking of the caspase site in APP did not affect A beta levels and, 3) caspase activation in cells by serum withdrawal did not increase A beta secretion. Thus, caspase cleavage of APP is unlikely to play a direct role in amyloidogenesis.

Alzheimer Disease↗

SB 239063, a novel p38 inhibitor, attenuates early neuronal injury following ischemia.

The aim of the present study was to evaluate p38 MAPK activation following focal stroke and determine whether SB 239063, a novel second generation p38 inhibitor, would directly attenuate early neuronal injury. Following permanent middle cerebral artery occlusion (MCAO), brains were dissected into ischemic and non-ischemic cortices and Western blots were employed to measure p38 MAPK activation. Neurologic deficit and MR imaging were utilized at various time points following MCAO to monitor the development and resolution of brain injury. Following MCAO, there was an early (15 min) activation of p38 MAPK (2.3-fold) which remained elevated up to 1 h (1.8-fold) post injury compared to non-ischemic and sham operated tissue. Oral SB 239063 (5, 15, 30, 60 mg/kg) administered to each animal 1 h pre- and 6 h post MCAO provided significant (P<0.05) dose-related neuroprotection reducing infarct size by 42, 48, 29 and 14%, respectively. The most effective dose (15 mg/kg) was further evaluated in detail and SB 239063 significantly (P<0.05) reduced neurologic deficit and infarct size by at least 30% from 24 h through at least 1 week. Early (i.e. observed within 2 h) reductions in diffusion weighted imaging (DWI) intensity following treatment with SB 239063 correlated (r=0.74, P<0.01) to neuroprotection seen up to 7 days post stroke. Since increased protein levels for various pro-inflammatory cytokines cannot be detected prior to 2 h in this stroke model, the early improvements due to p38 inhibition, observed using DWI, demonstrate that p38 inhibition can be neuroprotective through direct effects on ischemic brain cells, in addition to effects on inflammation.

Animals↗