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Biomedical subjects

M Deshpande

Publications and source records attributed to M Deshpande.

At least 19 recordsLinked to original sources
PubMed2006

Changing pattern of childhood blindness in Maharashtra, India.

AIM: To determine the causes of severe visual impairment and blindness in children in schools for the blind in Maharashtra, India. METHODS: Children aged <16 years with a visual acuity of <6/60 in the better eye, attending 35 schools for the blind were examined between 2002 and 2005, and causes were classified using the World Health Organization's system. RESULTS: 1985 students were examined, 1778 of whom fulfilled the eligibility criteria. The major causes of visual loss were congenital anomalies (microphthalmos or anophthalmos; 735, 41.3%), corneal conditions (mainly scarring; 395, 22.2%), cataract or aphakia (n = 107, 6%), and retinal disorders (mainly dystrophies; n = 199, 11.2%). More than one third of children (34.5%) were blind from conditions which could have been prevented or treated, 139 of whom were referred for surgery. Low vision devices improved near-acuity in 79 (4.4%) children, and 72 (4%) benefited from refraction. No variation in causes by sex or region was observed. CONCLUSIONS: Congenital anomalies accounted for 41% of blindness, which is higher than in a similar study conducted 10 years ago. Corneal scarring seems to be declining in importance, low vision and optical services need to be improved, and research is needed to determine the aetiology of congenital anomalies.

Adolescent↗
PubMed2005

Role of activated astrocytes in neuronal damage: potential links to HIV-1-associated dementia.

HIV-1-associated dementia (HAD) is an important complication of HIV-1 infection. Reactive astrogliosis is a key pathological feature in HAD brains and in other central nervous system (CNS) diseases. Activated astroglia may play a critical role in CNS inflammatory diseases such as HAD. In order to test the hypothesis that activated astrocytes cause neuronal injury, we stimulated primary human fetal astrocytes with HAD-relevant pro-inflammatory cytokine IL-1beta. IL-1beta-activated astrocytes induced apoptosis and significant changes in metabolic activity in primary human neurons. An FITC-conjugated pan-caspase inhibitor peptide FITC-VAD-FMK was used for confirming caspase activation in neurons. IL-1beta activation enhanced the expression of death protein FasL in astrocytes, suggesting that FasL is one of the potential factors responsible for neurotoxicity observed in HAD and other CNS diseases involving glial inflammation. Our data presented here add to the developing picture of role of activated glia in HAD pathogenesis.

Analysis of Variance↗
PubMed2003

Extracapsular cataract surgery compared with manual small incision cataract surgery in community eye care setting in western India: a randomised controlled trial.

AIM: To study "manual small incision cataract surgery (MSICS)" for the rehabilitation of cataract visually impaired and blind patients in community based, high volume, eye hospital setting; to compare the safety and effectiveness of MSICS with conventional extracapsular cataract surgery (ECCE). METHODS: In a single masked randomised controlled clinical trial, 741 patients, aged 40-90 years, with operable cataract were randomly assigned to receive either MSICS or ECCE and operated upon by one of eight participating surgeons. Intraoperative and postoperative complications were graded and scored according to the Oxford Cataract Treatment and Evaluation Team recommendations. The patients were followed up at 1 week, 6 weeks, and 1 year after surgery and their visual acuity recorded. RESULTS: This paper reports outcomes at 1 and 6 weeks. 706 of the 741(95.3%) patients completed the 6 week follow up. 135 of 362 (37.3%) of ECCE group and 165 of 344 (47.9%) of MSICS group had uncorrected visual acuity of 6/18 or better after 6 weeks of follow up. 314 of 362 (86.7%) of ECCE group and 309 of 344 (89.8%) of MSICS group had corrected postoperative vision of 6/18 or better. Four of 362 (1.1%) of ECCE group and six of 344 (1.7%) of MSICS group had corrected postoperative visual acuity less than 6/60. There were no significant differences between the two groups for intraoperative and severe postoperative complications. CONCLUSION: MSICS and ECCE are both safe and effective techniques for treatment of cataract patients in community eye care settings. MSICS needs similar equipment to ECCE, but gives better uncorrected vision.

Adult↗
PubMed2003

Is manual small incision cataract surgery affordable in the developing countries? A cost comparison with extracapsular cataract extraction.

AIM: To compare the cost of manual small incision cataract surgery (MSICS) with conventional extracapsular cataract surgery (ECCE) in community eye care settings. METHOD: A single masked randomised trial was used to compare the safety, efficacy, time, and patient satisfaction of surgery by both the techniques. The fixed facility and recurrent cost for the two procedures was calculated based on information collected from different sources. Average cost per procedure was calculated by dividing the total cost by the number of procedures performed. RESULT: The average cost of an ECCE procedure for the hospital was Rs 727.76 (US$15.82) and the average cost of a MSICS procedure was Rs 721.40 ($15.68), of which Rs. 521.51 ($11.34) was the fixed facility cost common to both. CONCLUSION: Both ECCE and MSICS are economical in community eye care settings, but MSICS is economical and gives better uncorrected visual acuity in a greater proportion of patients.

Cataract Extraction↗
PubMed2002

2-Aminoethoxydiphenyl borate inhibits phototransduction and blocks voltage-gated potassium channels in Limulus ventral photoreceptors.

2-Aminoethoxydiphenyl borate (2-APB) is a membrane-permeable modulator that inhibits the activation of inositol (1,4,5) trisphosphate (InsP(3)) receptors, store operated channels (SOCs) and TRP channels in cells that utilize the phosphoinositide cascade for cellular signaling. In Limulus ventral photoreceptors, light-induced calcium release via the phosphoinositide cascade is thought to activate the photocurrent. Injection of either exogenous InsP(3) or calcium ions can therefore mimic excitation by light. One hundred micromolar 2-APB reversibly inhibited the photocurrent of ventral photoreceptors in a concentration-dependent manner, acting on at least two processes thought to mediate the visual cascade. 2-APB reversibly inhibited both light and InsP(3)-induced calcium release, consistent with its role as an inhibitor of the InsP(3) receptor. In addition, 2-APB reversibly inhibited the activation of depolarizing current flow through the plasma membrane caused by pulsed pressure injection of calcium ions into the light-sensitive lobe of the photoreceptor. We also found that 100 micro M 2-APB reversibly inhibited both transient and sustained voltage-activated potassium current during depolarizing steps. 2-APB has previously been shown to block phototransduction in Drosophila photoreceptors. The lack of specificity of the action of 2-APB in Limulus indicates that this blockade need not necessarily arise from inhibition of InsP(3)-induced calcium release.

Animals↗
PubMed2001

Copolymers of amine methacrylate with poly(ethylene glycol) as vectors for gene therapy.

A series of structurally related copolymers of tertiary amine methacrylate with poly(ethylene glycol) (PEG) were investigated for their potential to serve as vectors for gene therapy. The effects of copolymer structure on the complexation and transfection ability were assessed. The ability of the PEG-based copolymers and DMAEMA homopolymer to bind and condense DNA was confirmed by gel electrophoresis, ethidium bromide displacement and transmission electron microscopy. The presence of PEG in the copolymers had a beneficial effect on their ability to bind to DNA. Colloidally stable complexes were obtained for all the PEG-copolymer systems as shown by uniformly discrete spherical images from transmission electron microscopy and approximate diameters of 80-100 nm by dynamic light scattering studies. DMAEMA homopolymer, however, produced agglomerated particles, confirming the important role played by the PEG chains in producing compact stable DNA complexes. Assessment of the effect of ionic strength of the buffer on the complexation and dissociation of the complexes indicated the importance of both electrostatic and non-electrostatic interactions in the polymer-DNA complexation. In vitro transfection experiments showed that DMAEMA homopolymer gave the highest level of transfection comparable to a control poly-L-lysine (PLL) system. The PEG-based copolymers gave reduced levels of transfection, most likely due to the steric stabilization effect of a PEG corona.

DNA↗
PubMed2001

Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression.

CD28, described as a T cell costimulatory molecule so far, is expressed on human peripheral blood neutrophils, as shown by cell surface staining and immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of CD28 on these cells can be blocked by actinomycin D, an RNA transcription inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28 results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is down-regulated by receptor internalization 3 h after CD28 cross-linking with concurrent decrease in IL-8-induced chemotactic migration. Thus, our results demonstrate for the first time that CD28 is expressed on human peripheral blood neutrophils and that CD28 may play an important role in the regulation of IL-8RA expression and migration of neutrophils in response to IL-8.

Adult↗
PubMed2001

Biodegradation of 1,4-dioxane in planted and unplanted soil: effect of bioaugmentation with Amycolata sp. CB1190.

1,4-Dioxane is one of the most recalcitrant and toxic contaminants in the subsurface. This study investigated the potential to enhance dioxane biodegradation in both planted and unplanted soil, by adding the dioxane-degrading actinomycete, Amycolata sp. CB1190. Dioxane was not removed within 120 days in sterile controls or in viable microcosms not amended with CB 1190. Poplar root extract (40 mg/L as COD) stimulated dioxane degradation in bioaugmented soil, and 100 mg/L dioxane were removed within 45 days. Other co-substrates that enhanced dioxane degradation by CB1190 include tetrahydrofuran (THF) and 1-butanol, while glucose and soil extract did not affect dioxane degradation. The stimulatory effect of THF was partly due to enhanced enzyme induction, while that of root extract and 1-butanol was attributed to additional growth of CB1190. In another experiment with dioxane added at 10 mg/kg-soil. reactors planted with hybrid poplar trees removed (by evapotranspiration and biodegradation in the root zone) more dioxane within 26 days than unplanted reactors, regardless of whether CB1190 was added. Nevertheless, CB1190 enhanced mineralization of [14C]-dioxane in all experiments. This enhancement was more pronounced in unplanted soil because plant uptake reduced the availability of dioxane for microbial degradation. These results suggest that bioaugmented phytoremediation is an attractive alternative to remove dioxane from shallow contaminated sites.

Actinomycetales↗
PubMed2001

Beneficial effect of supplementation with copper sulfate on STZ-diabetic mice (IDDM).

Trace element status is known to be altered in the diabetic state. Current evidence suggests that reactive oxygen intermediates (ROI's) do participate in the destruction of pancreatic beta cells in STZ-induced Type 1 diabetes. The copper and zinc status of diabetic patients and their descendants was also found to have changed. The aim of this study was to evaluate the potential usefulness of copper sulfate in the treatment of STZ-induced type I diabetes. We used C57BL6 female mice, in whom copper sulfate treatment was started at 6 weeks of age followed by an IP injection of 40 mg/kg body weight of STZ for five consecutive days. Its effects were evaluated at 10 weeks of age. The treatment with copper sulfate significantly decreased blood glucose levels, levels of lipid peroxidation and mRNA expression of the enzyme iNOS and the cytokines IFN-gamma and IL-4. Histological analysis of the pancreas revealed that, three out of five animals in the copper sulfate treated groups showed absence of mononuclear cell infiltration and no change in the shape and size of islets as compared to pancreas of the STZ-induced diabetic group of animals. In conclusion, our observations indicate that copper sulfate treatment can exert beneficial effects in diabetes with preservation of beta-cell function in vivo. Copper sulfate could be exerting these beneficial effects either by acting directly by reducing free radicals or through reduction in glucose levels.

Animals↗
PubMed2000

A short formal synthesis of squalamine from a microbial metabolite.

A short formal synthesis of squalamine is described, utilizing the biotransformation product 2, which is available in one step from commercially available 3-keto-23,24-bisnorchol-4-en-22-ol (1). Regioselective C-22 oxidation and C-24 sulfation of the corresponding alcohols in the presence of a free C-7 alcohol make for an efficient preparation of squalamine intermediate 11.

Angiogenesis Inhibitors↗
PubMed2000

Salicylamide inhibitors of influenza virus fusion.

Structural variation of the quinolizidine heterocycle of the influenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identification of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a plaque reduction assay.

Animals↗
PubMed2000

The inositol 1,4,5-trisphosphate receptor is required for maintenance of olfactory adaptation in Drosophila antennae.

A role for inositol 1,4,5-trisphosphate (IP(3)) as a second messenger during olfactory transduction has been postulated in both vertebrates and invertebrates. However, given the absence of either suitable pharmacological reagents or mutant alleles specific for the IP(3) signaling pathway, an unequivocal demonstration of IP(3) function in olfaction has not been possible. Here we have investigated the role of a well-established cellular target of IP(3)-the IP(3) receptor (IP(3)R)-in olfactory transduction in Drosophila. For this purpose we tested existing viable combinations of IP(3)R mutant alleles, as well as a newly generated set of viable itpr alleles, for olfactory function. In all of the viable allelic combinations primary olfactory responses were found to be normal. However, a subset of itpr alleles (including a null allele) exhibit faster recovery after a strong pulse of odor, indicating that the IP(3)R is required for maintenance of olfactory adaptation. Interestingly, this defect in adaptation is dominant for two of the alleles tested, suggesting that the mechanism of adaptation is sensitive to levels of the IP(3)R.

Action Potentials↗
PubMed1999

PREDICT: A simple risk score for clinical severity and long-term prognosis after hospitalization for acute myocardial infarction or unstable angina: the Minnesota heart survey.

BACKGROUND: We evaluated short- and long-term mortality risks in 30- to 74-year-old patients hospitalized for acute myocardial infarction or unstable angina and developed a new score called PREDICT. METHODS AND RESULTS: PREDICT was based on information routinely collected in hospital. Predictors abstracted from hospital record items pertaining to the admission day, including shock, heart failure, ECG findings, cardiovascular disease history, kidney function, and age. Comorbidity was assessed from discharge diagnoses, and mortality was determined from death certificates. For 1985 and 1990 hospitalizations, the 6-year death rate in 6134 patients with 0 to 1 score points was 4%, increasing stepwise to 89% for >/=16 points. Score validity was established by only slightly attenuated mortality prediction in 3570 admissions in 1970 and 1980. When case severity was controlled for, 6-year risk declined 32% between 1970 and 1990. When PREDICT was held constant, 24% of those treated with thrombolysis died in 6 years compared with 31% of those not treated. CONCLUSIONS: The simple PREDICT risk score was a powerful prognosticator of 6-year mortality after hospitalization.

Adult↗
PubMed1999

pH-dependent changes in photoaffinity labeling patterns of the H1 influenza virus hemagglutinin by using an inhibitor of viral fusion.

The hemagglutinin (HA) protein undergoes a low-pH-induced conformational change in the acidic milieu of the endosome, resulting in fusion of viral and cellular membranes. A class of compounds that specifically interact with the HA protein of H1 and H2 subtype viruses and inhibit this conformational change was recently described (G. X. Luo et al., Virology 226:66-76, 1996, and J. Virol. 71:4062-4070, 1997). In this study, purified HA trimers (bromelain-cleaved HA [BHA]) are used to examine the properties and binding characteristics of these inhibitors. Compounds were able to inhibit the low-pH-induced change of isolated trimers, as detected by resistance to digestion with trypsin. Protection from digestion was extremely stable, as BHA-inhibitor complexes could be incubated for 24 h in low pH with almost no change in BHA structure. One inhibitor was prepared as a radiolabeled photoaffinity analog and used to probe for specific drug interactions with the HA protein. Analysis of BHA after photoaffinity analog binding and UV cross-linking revealed that the HA2 subunit of the HA was specifically radiolabeled. Cross-linking of the photoaffinity analog to BHA under neutral (native) pH conditions identified a stretch of amino acids within the alpha-helix of HA2 that interact with the inhibitor. Interestingly, cross-linking of the analog under acidic conditions identified a different region within the HA2 N terminus which interacts with the photoaffinity compound. These attachment sites help to delineate a potential binding pocket and suggest a model whereby the BHA is able to undergo a partial, reversible structural change in the presence of inhibitor compound.

Amino Acid Sequence↗
PubMed1995

Rapid large-scale growth of Helicobacter pylori in flasks and fermentors.

We developed procedures for large-scale cultivation of Helicobacter pylori in flasks and fermentors. Flasks incubated closed under a microaerophilic gas phase with a cotton plug covered by a plastic bag, followed by removal of the bag after 8 h, gave excellent growth. Growth in a 10-liter fermentor led to excessive foaming if the medium was sparged with gas; silicone- or polyglycol-based antifoaming agents were severely inhibitory. Use of fermentor surface gassing, first with a microaerophilic 6% oxygen gas mixture, then with air, and then with 95% oxygen, allowed the culture to grow to an A600 of 2.5 in < 24 h. This method was modified for scale-up to a 100-liter fermentor.

Culture Media↗