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Biomedical subjects

S S Deshpande

Publications and source records attributed to S S Deshpande.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral dose from uniform dynamic multileaf collimation fields: implications for sliding window intensity-modulated radiotherapy.

The increase in the number of monitor units in sliding window intensity-modulated radiotherapy, compared with conventional techniques for the same target dose, may lead to an increase in peripheral dose (PD). PD from a linear accelerator was measured for 6 MV X-ray using 0.6 cm3 ionization chamber inserted at 5 cm depth into a 35 cm x 35 cm x 105 cm plastic water phantom. Measurements were made for field sizes of 6 cm x 6 cm, 10 cm x 10 cm and 14 cm x 14 cm, shaped in both static and dynamic multileaf collimation (DMLC) mode, employing strip fields of fixed width 0.5 cm, 1.0 cm, 1.5 cm, and 2.0 cm, respectively. The effect of collimator rotation and depth of measurement on peripheral dose was investigated for 10 cm x 10 cm field. Dynamic fields require 2 to 14 times the number of monitor units than does a static open field for the same dose at the isocentre, depending on strip field width and field size. Peripheral dose resulting from dynamic fields manifests two distinct regions showing a crest and trough within 30 cm from the field edge and a steady exponential fall beyond 30 cm. All dynamic fields were found to deliver a higher PD compared with the corresponding static open fields, being highest for smallest strip field width and largest field size; also, the percentage increase observed was highest at the largest out-of-field distance. For 6 cm x 6 cm field, dynamic fields with 0.5 cm and 2 cm strip field width deliver PDs 8 and 2 times higher than that of the static open field. The corresponding factors for 14 cm x 14 cm field were 15 and 6, respectively. The factors by which PD for DMLC fields increase, relative to jaws-shaped static fields for out-of-field distance beyond 30 cm, are almost the same as the corresponding increases in the number of monitor units. Reductions of 20% and 40% in PD were observed when the measurements were done at a depth of 10 cm and 15 cm, respectively. When the multileaf collimator executes in-plane (collimator 90 degrees) motion, peripheral dose decreases by as much as a factor of 3 compared with cross-plane data. The knowledge of PD from DMLC field is necessary to estimate the increase in whole-body dose and the likelihood of radiation induced secondary malignancy.

Humans↗
PubMed2006

Ovarian and uterine ultrasonography in healthy girls between birth to 18 years.

The aim of our study was to determine the pattern of female reproductive organ growth in Indian girls from birth to 18 years of age and to correlate the uterine length, mean ovarian volume (MOV) and Fundo Cervical Ratio (FCR) with chronological age, bone age and pubertal breast staging. A cross sectional study was performed on 218 girls from birth to 18 years of age. Height, weight, stage of puberty, X-ray for bone age and transabdominal ultrasounds were performed on all girls. Higher chronological age, bone age and increase in breast stage significantly predicted higher MOV (P < 0.001) and higher uterine length (P < 0.001). The MOV, uterine length and FCR are positively correlated with chronological age, bone age, height, weight and breast staging. Data from present study may be useful in screening cases of precocious puberty and other disorders that may need further evaluation.

Adolescent↗
PubMed2004

Changing epidemiology of neonatal septic arthritis.

PURPOSE: To study the changing epidemiological pattern of micro-organisms as an aetiology of septic arthritis, and to correlate the pattern with the outcome of neonatal septic arthritis, in terms of joint function and morphology. METHODS: 15 consecutive cases of neonatal septic arthritis of hip admitted between 1999 and 2002 were studied. Diagnosis of septic arthritis was made on the basis of Morrey's criteria. All patients were treated by arthrotomy after aspiration of purulent fluid from the joint. Patients were followed up for a mean period of 2.4 years. Clinical and radiological examinations were performed at follow-up. RESULTS: The mean age of the 15 patients was 20.35 days. 13 (87%) patients had primary septic arthritis, while only 2 (13%) had associated osteomyelitis. Culture reports revealed that the spectrum consisted of 33% gram-negative organisms, 7% fungal, and only 20% gram-positive organisms-Staphylococcus aureus in 3 patients, Klebsiella in 2 patients, one each of Proteus, Candida, Escherichia coli, and Enterobactor. Six patients were pus-cell positive with negative culture. No organism was found in 6 (40%) cases. Investigations showed leukocytosis, raised C-reactive protein and erythrocyte sedimentation rate in all 15 patients. 12 patients had normal clinical and radiological parameters at follow-up. Three patients had delayed surgical drainage of more than 72 hours due to late presentation, and showed various radiological sequelae with terminal restriction of joint movements. CONCLUSION: There are more cases of primary septic arthritis than secondary septic arthritis. Clinicians should be alert of the aetiology shift to gram-negative organisms, in addition to fungal and gram-positive ones. Arthrotomy to drain pus from the joint should not be delayed. Better long-term results can be achieved by early surgical drainage and immediate antibiotic coverage.

Anti-Bacterial Agents↗
PubMed2002

Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis.

The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS) production, whereas the DNA repair enzyme and transcriptional regulator redox factor-1 (ref-1) protects against cell death due to oxidative stimuli. However, the function of ref-1 in regulating intracellular oxidative stress, particularly that induced by rac1, has not been defined. We examined the role of ref-1 in vascular endothelial cell oxidative stress and apoptosis. Ref-1 was expressed in both the cytoplasm and nuclei of resting endothelial cells. Cytoplasmic ref-1 translocated to the nucleus with the oxidative trigger hypoxia/reoxygenation (H/R). Forced cytoplasmic overexpression of ref-1 suppressed H/R-induced oxidative stress (H(2)O(2) production), NF-kappaB activation, and apoptosis, and also mitigated rac1-regulated H(2)O(2) production and NF-kappaB transcriptional activity. We conclude that inhibition of oxidative stress is another mechanism by which ref-1 protects against apoptosis, and that this is achieved through modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel extra-nuclear function of ref-1.

Adenoviridae↗
PubMed2002

Oxidant signalling in carcinogenesis: a commentary.

It is becoming increasingly evident that reactive oxygen species (ROS) act at different stages of carcinogenesis, and thus play multiple roles in oncogenesis. In addition to being mutagenic and initiating tumors, ROS or carcinogens that result in ROS generation may affect tumor promotion and progression through varied effects on growth promoting, growth inhibitory, or apoptotic signaling pathways.

Apoptosis↗
PubMed2002

Adiposity and hyperinsulinemia in Indians are present at birth.

We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; -1.52 SD score; confidence interval (CI), -1.66, -1.42] and had smaller abdominal (-2.39 SD score; CI, -2.52, -2.09), midarm (-1.47 SD score; CI, -1.58, -1.34), and head (-1.23 SD score; CI, -1.42, -1.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (-0.32 SD score; CI, -0.43, -0.20) was better preserved than triceps (peripheral) skinfold (-0.86 SD score; CI, -0.97, -0.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were comparable in the two populations but were higher in Indians when adjusted for birth weight, confirming relative adiposity and hyperinsulinemia of Indian babies. Indian mothers were smaller in all respects, compared with white Caucasian mothers, except subscapular skinfold, which was similar in the two populations. Our results support the intrauterine origin of adiposity, central adiposity, and hyperinsulinemia in Indians. Further research should concentrate on elucidating genetic and environmental influences on fetal growth and body composition. Prevention of insulin resistance syndrome in Indians will need to address regulation of fetal growth in addition to prevention of obesity in later life.

Adipose Tissue↗
PubMed2001

Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism.

Vascular endothelial growth factor (VEGF) is a potent vascular endothelial cell-specific mitogen that modulates endothelial cell function. In the present study, we show that VEGF induces manganese-superoxide dismutase (MnSOD) mRNA and protein in human coronary artery endothelial cells (HCAEC) and pulmonary artery endothelial cells. VEGF-mediated induction of MnSOD mRNA was inhibited by pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI), and 4-(2-aminoethyl)-benzenesulfonyl fluoride, but not with the nitric oxide synthase inhibitor L-NAME (N-monomethyl-L-arginine) or the xanthine oxidase inhibitor allopurinol. VEGF stimulation of MnSOD was also inhibited by adenoviral-mediated overexpression of catalase Cu, Zn-SOD and a dominant-negative form of the small GTPase component of NADPH oxidase Rac1 (Rac1N17). Treatment of HCAEC with VEGF resulted in a transient increase in ROS production at 20 min, as measured by 2,7-dichlorodihydrofluorescein oxidation. This effect was abrogated by expression of Rac1N17. Taken together, these findings suggest that VEGF induces MnSOD by an NADPH oxidase-dependent mechanism and that VEGF signaling in the endothelium is coupled to the redox state of the cell.

Adenoviridae↗
PubMed2001

Anomalous enhancement of botulinum toxin type A neurotoxicity in the presence of antitoxin.

The neutralization of botulinum toxin serotype A with polyclonal equine antitoxin was studied in isolated mouse hemidiaphragms and compared to the same action in live mice. The biological activity of the toxin in the isolated muscle could be markedly reduced with excess antitoxin, estimated as 3:1 molar ratios of IgG Ab:toxin or better. Toxin neutralization in vivo required higher ratios of Ab:toxin, ranging from 30:1 at high toxin doses and increasing to 100:1 at 10xLD50 toxin. At equimolar Ab to toxin ratios in the isolated muscle, the biological activity of the toxin underwent a statistically significant increase. This paradoxical effect of the polyclonal antisera was serotype selective and independent of the presence or absence of hemagglutinin in the toxin. The enhancement of toxin activity was subsequently localized to occupancy of one of four epitopes on the toxin using monoclonal antibodies to mimic the effect of the antitoxin. The enhancement of toxin activity suggests that botulinum toxin may undergo a conformational change upon binding antibodies to certain domains. This phenomenon could contribute to the observed concentration dependent changes in neutralization efficacy with antitoxin in vivo.

Animals↗
PubMed2001

Neuromuscular transmission and muscle contractility in SNAP-25-deficient coloboma mice.

Synaptosomal associated protein of 25 kDa (SNAP-25) is a cytoplasmic protein that participates in the docking and fusion of synaptic vesicles with the nerve terminal in preparation for neurotransmitter release. SNAP-25 is also a substrate for three of the seven serotypes of botulinum neurotoxin (BoNT). Intoxication by BoNT/A, /C1 or /E results in weakness and paralysis of skeletal muscle due to cleavage of SNAP-25 (and syntaxin la in the case /C1) at discrete serotype-specific sites. To elucidate the role of SNAP-25 in muscle function in more detail, contractility and neuromuscular transmission were studied in a mutant mouse model termed coloboma. The coloboma mutation results from a contiguous deletion of 1-2 centiMorgans on chromosome 2, which includes the entire SNAP-25 locus and three other identified genes. Homozygotes do not survive beyond gestation day 6; heterozygotes (Cm/+) have a normal life-span but express reduced levels of SNAP-25 mRNA and protein in the brain. The consequences of the Cm/+ mutation on twitch and tetanic tension, quantal release of neurotransmitter and spinal motoneuron expression of SNAP-25 were examined in the present study. Contrary to expectations, Cm/+ mice exhibited no alteration in twitch tension and generated normal tetanic tension even at the highest frequency examined (800 Hz). Microelectrode recordings revealed that MEPP amplitude and frequency were both within control limits. The ventral spinal cord of Cm/+ mice showed no deficiency in SNAP-25 content and immunohistochemical examination of nerve terminals in Cm/+ mice disclosed that SNAP-25 levels and distribution were similar to those of control mice. It is concluded that spinal motor neurons up-regulate SNAP-25 to preserve vital neuromuscular function.

Aminopyridines↗
PubMed2001

Principles and applications of luminescence spectroscopy.

Advances in instrumentation during the last decade as well as the ease with which the technology could be adapted to a wide variety of assay platforms has truly made luminescence spectroscopy the analytical method of choice in several diverse disciplines of life sciences. The primary reasons for its growing popularity are twofold: the use of nonisotopic labels and its exquisite sensitivity. Analyte concentrations as low as 10(-10) to 10(-12) M can be easily detected, while luminometry can detect biological events at concentrations as low as 10(-18) M. This is in contrast to absorption and NMR spectroscopic techniques, which require, respectively, 10(-8) M and 10(-5) M concentrations of the compound of interest. Furthermore, in several variations of this technology, the measurement itself can be nondestructive and noninvasive. Despite the fact that luminescence spectroscopic techniques provide some of the most sensitive and selective analytical methods, they have not yet been widely used in both basic and applied food research. The only exception to this is the growing popularity of the commercially available ATP bioluminescence kits used routinely for monitoring the cleanliness of work surfaces in the food industry. This review describes some of the relevant basic aspects of luminescence, several popular variations of this technology, and their potential uses in food research.

Enzymes↗
PubMed2001

Effects of turmeric on the activities of benzo(a)pyrene-induced cytochrome P-450 isozymes.

Turmeric and/or its main coloring component, curcumin (diferuloylmethane), have been shown to inhibit benzo(a)pyrene [B(a)P]-induced forestomach papillomas in mice. However, the mechanisms of turmeric-mediated chemoprevention are not well understood. To study the mechanisms of turmeric-mediated chemoprevention, we investigated the effects of turmeric feeding on the activities of isozymes of cytochrome P-450 (CYP450)--namely, ethoxyresorufin O-deethylase (EROD, CYP1A1) and methoxyresorufin O-demethylase (MROD, CYP1A2)--which are predominantly involved in the metabolism of B(a)P. We determined the activities of EROD and MROD by monitoring the formation of resorufin from respective substrates in the presence of microsomal proteins obtained from tissues of control, 1% turmeric, 1 mg B(a)P, and 1% turmeric + 1 mg B(a)P-fed Swiss mice. The results indicate that the administration of turmeric through diet significantly inhibited the activities of both EROD and MROD in forestomach (target organ), liver, and lung. In vitro studies employing curcumin, demethoxycurcumin, and bis-demethoxycurcumin suggest that curcumins are the inhibitors in turmeric. Inhibition of B(a)P metabolizing phase I enzymes (EROD, MROD) may be at least in part one of the possible modes of chemopreventive action of turmeric/curcumin.

Animals↗
PubMed2000

Rac1 regulates stress-induced, redox-dependent heat shock factor activation.

The signaling pathway by which environmental stresses activate heat shock factors (HSFs) is not completely understood. We show that the small GTPase rac1, and Rac1-regulated reactive oxygen species (ROS) play an important role in stress-stimulated heat shock response. A dominant-negative allele of Rac1 (Rac1N17) inhibits the hypoxia/reoxygenation and sodium arsenite-induced transcriptional activity of HSF-1 and the transcription of heat shock protein 70. Rac1N17 also suppresses the production of intracellular ROS induced by hypoxia/reoxygenation or sodium arsenite. Moreover, direct suppression of intracellular ROS levels by antioxidants decreases stress-stimulated HSF activity. However, expression of a constitutively active mutant of Rac1 (Rac1V12) in the absence of extracellular stresses does not increase intracellular ROS levels or induce the heat shock response. These results show that Rac1 is a necessary but insufficient component of the stress-induced signaling pathway that leads to ROS production, activation of HSFs, and transcription of heat shock proteins.

Adenoviridae↗
PubMed2000

Antagonism of botulinum toxin A-mediated muscle paralysis by 3, 4-diaminopyridine delivered via osmotic minipumps.

The ability of 3,4-diaminopyridine (3,4-DAP) to antagonize muscle paralysis following local injection of botulinum neurotoxin A (BoNT/A) complex was evaluated in the in situ rat extensor digitorum longus (EDL) preparation. The minipumps were implanted 6 h prior to BoNT/A administration and delivered their contents over a 7-day period producing a steady plasma 3,4-DAP concentration of 27-29 microM. In the absence of 3,4-DAP, a local injection of five mouse LD(50) units of BoNT/A led to total paralysis of EDL muscles within 24 h of application. Recovery from paralysis was slow, remaining at <30% of control 14 days after toxin injection. 3,4-DAP delivery by osmotic minipumps antagonized the actions of BoNT/A on neuromuscular transmission. Seven days after the onset of 3,4-DAP infusion, indirectly elicited twitch and tetanic tensions in BoNT/A-injected EDL muscles were 72.4 and 46.9% of control, respectively. In the absence of 3,4-DAP, twitch and tetanic tensions were only 5.4 and 15. 1% of control. The benefits conferred by 3,4-DAP treatment were not maintained after minipumps were removed. Seven days after cessation of 3,4-DAP infusion, twitch and tetanic tensions were not significantly different from those observed in muscles receiving BoNT/A alone. It is concluded that 3,4-DAP may be useful for treatment of BoNT/A-induced muscle paralysis, but sustained delivery of the drug would be required for the entire period of BoNT intoxication to maintain muscle function.

4-Aminopyridine↗
PubMed2000

Development of a monoclonal antibody-based cELISA for the analysis of sulfadimethoxine. 1. Development and characterization of monoclonal antibodies and molecular modeling studies of antibody recognition.

Sulfonamide antibiotics are used to treat a variety of bacterial and protozoan infections in cattle, swine, and poultry. Current residue methods for the analysis of sulfonamides in animal-based food products include bioassays, chromatographic methods (HPLC, GLC), and immunoassays. Most immunoassays have employed highly specific polyclonal antibodies. In this paper, we describe the isolation of monoclonal antibodies against sulfadimethoxine (SDM) that vary in their sensitivities and cross-reactivities against a large number of sulfonamides. The most sensitive monoclonal antibody, designated SDM-18, exhibits an IC(50) value for SDM of 1.53 ppb. Another monoclonal antibody, designated SDM-44, exhibits IC(50) values for six sulfonamides well below the established threshold level of 100 ppb for animal tissues. Molecular modeling studies of the cross-reactive drugs suggest that, depending on the monoclonal antibody, both steric and electronic features govern antibody binding. Due to the diversity of these monoclonal antibodies, it should be possible to design both compound- and class-specific monoclonal antibody-based immunoassays.

Animals↗
PubMed2000

Development of a monoclonal antibody-based cELISA for the analysis of sulfadimethoxine. 2. Evaluation of rapid extraction methods and implications for the analysis of incurred residues in chicken liver tissue.

Several rapid extraction methods were evaluated for use with a monoclonal antibody-based competitive inhibition ELISA (cELISA) to detect sulfadimethoxine (SDM) in chicken liver tissue. These methods included extraction of the samples with (1) aqueous buffer with or without ultrafiltration, (2) acetonitrile/water, (3) methanol/water, or (4) acetone. The organic extraction methods were evaluated with or without solvent evaporation prior to dilution into assay buffer for the cELISA. The aqueous-based extraction methods were compatible with the cELISA. However, of the organic extraction methods, only the acetone liver extract with solvent evaporation prior to analysis was compatible with the cELISA. The cELISA method coupled to aqueous- or acetone-based sample extraction as well as an HPLC method was evaluated for the analysis of chicken liver tissues fortified with SDM at levels from 0.2 to 0.025 ppm. Mean SDM recoveries for the HPLC method and for the cELISA method using samples prepared by aqueous extraction, aqueous extraction and ultrafiltration, or acetone extraction, evaporation, and reconstitution were 68.9, 95.7, 60.1, and 52.5%, respectively. For the analysis of samples obtained from an SDM incurred residue study, HPLC and cELISA analysis of the same organic extract gave results that were highly correlated (R(2) = 0.976; p < 0.0001). However, results obtained from the analysis of aqueous extracts by cELISA did not correlate well with those obtained by HPLC (R(2) = 0.61, p > 0. 0006). This was attributed to the coextraction of cross-reactive SDM-related residues that were not quantified by the HPLC method. The presence of these residues should be considered during data interpretation when ELISA methods coupled with rapid aqueous extraction of samples are used in SDM residue monitoring programs.

Animals↗
PubMed2000

Inhibition of the Rac1 GTPase protects against nonlethal ischemia/reperfusion-induced necrosis and apoptosis in vivo.

Reperfusion of ischemic tissue results in the generation of reactive oxygen species that contribute to tissue injury. The sources of reactive oxygen species in reperfused tissue are not fully characterized. We hypothesized that the small GTPase Rac1 mediates the oxidative burst in reperfused tissue and thereby contributes to reperfusion injury. In an in vivo model of mouse hepatic ischemia/reperfusion injury, recombinant adenoviral expression of a dominant negative Rac1 (Rac1N17) completely suppressed the ischemia/reperfusion-induced production of reactive oxygen species and lipid peroxides, activation of nuclear factor-kappa B, and resulted in a significant reduction of acute liver necrosis. Expression of Rac1N17 also suppressed ischemia/reperfusion-induced acute apoptosis. The protection offered by Rac1N17 was also evident in knockout mice deficient for the gp91phox component of the phagocyte NADPH oxidase. This work demonstrates the crucial role of a Rac1-regulated oxidase in mediating the production of injurious reactive oxygen species, which contribute to acute necrotic and apoptotic cell death induced by ischemia/reperfusion in vivo. Targeted inhibition of this oxidase, which is distinct from the phagocyte NADPH oxidase, should provide a new avenue for in vivo therapy aimed at protecting organs at risk from ischemia/reperfusion injury.-Ozaki, M., Deshpande, S. S., Angkeow, P., Bellan, J., Lowenstein, C. J., Dinauer, M. C., Goldschmidt-Clermont, P. J., Irani, K. Inhibition of the Rac1 GTPase protects against nonlethal ischemia/reperfusion-induced necrosis and apoptosis in vivo.

Animals↗