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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 541 records · Page 30Linked to original sources
PubMed1996

Hypolipidaemic effect of fruit juice of Emblica officinalis in cholesterol-fed rabbits.

The lipid lowering and antiatherosclerotic effects of Emblica officinalis (Amla) fresh juice were evaluated in cholesterol-fed rabbits (rendered hyperlipidaemic by atherogenic diet and cholesterol feeding). E. officinalis fresh juice was administered at a dose of 5 ml/kg body weight per rabbit per day for 60 days. Serum cholesterol, TG, phospholipid and LDL levels were lowered by 82%, 66%, 77% and 90%, respectively. Similarly, the tissue lipid levels showed a significant reduction following E. officinalis juice administration. Aortic plaques were regressed. E. officinalis juice treated rabbits excreted more cholesterol and phospholipids, suggesting that the mode of absorption was affected. E. officinalis juice is an effective hypolipidaemic agent and can be used as a pharmaceutical tool in hyperlipidaemic subjects.

Animals↗
PubMed1996

Surfactant rescue in the fetal lamb model of congenital diaphragmatic hernia.

Surfactant therapy given before the onset of ventilation (surfactant prophylaxis) has been shown to improve oxygenation, ventilation, and pulmonary hemodynamics in the lamb model of congenital diaphragmatic hernia (CDH). The aim of this study was to assess the efficacy of surfactant administered after the onset of ventilation ("surfactant rescue"). Ten lambs with surgically created CDH were instrumented, at full term, to measure pulmonary blood flow and pulmonary vascular resistance (PVR). Catheters also were positioned for monitoring of systemic blood pressure and arterial blood gases. The animals were delivered and pressure-ventilated according to a standard protocol (PIP, 30 cm; PEEP, 4 cm; respiratory rate, 60 breaths per minute). After 30 minutes of ventilation, five animals received an intratracheal dose of calf lung surfactant extract (50 mg/kg). The animals were studied for 4 hours. Surfactant rescue had no discernible effect on Pco2, Pco2, or pH. There was an increase in pulmonary blood flow, but it was not significant. The dramatic improvement in oxygenation, ventilation, and pulmonary blood flow found with prophylactic surfactant cannot be reproduced when surfactant is administered as rescue therapy. This indicates that the surfactant is not being delivered adequately, the lungs have already incurred significant barotrauma, and/or the surfactant is being inactivated by alveolar protein. Therefore, the authors suggest that when exogenous surfactant therapy is being considered for the fetus or newborn with CDH, it should be administered as early as possible, preferably before the infant's first breath. Prenatal diagnosis and delivery in a tertiary care center would facilitate this optimum management.

Animals↗
PubMed1996

Can cardiac weight predict lung weight in patients with congenital diaphragmatic hernia?

Left ventricular disproportion (decreased left-to-right ventricular internal diameter ratio) has been correlated with fetal or neonatal survival in cases of congenital diaphragmatic hernia (CDH). Because cardiac development is intimately related to lung development in the normally developing fetus, the authors sought to determine whether cardiac weight correlates with lung weight in control and CDH lambs at term. Twenty lambs had CDH created surgically at 80 days' gestation and were sacrificed at term for measurement of lung and heart weight. Nine unoperated lambs served as controls. Analysis of the relationship between heart weight and lung weight was performed for both groups, and regression curves were generated as mean +/- 2 standard deviations (SD) for each group of lambs. All data are expressed in grams. For CDH lambs, the relationship between heart and lung weight is as follows: lung weight = 0.69 x heart weight + 37 g. For control lambs, the equation is: lung weight = -0.004 x heart weight + 135 g. There is no overlap of these regression curves at 2 SD of the mean. The curves differ significantly, and the P value exceeds .05. The results suggest that cardiac weight can be used to predict lung weight in CDH and control lambs at term. The authors speculate that this difference in weight is attributable to underdevelopment of the left ventricle in CDH. Given that left ventricular disproportion has been described as early as the pseudoglandular stage of lung development in human fetuses with CDH, it is hoped that echocardiographic parameters can be used to differentiate the fetuses with adequate lung volume from those whose lung volume is incompatible with extrauterine life. Patients in the latter group may benefit from surgical correction of the diaphragmatic defect in utero.

Analysis of Variance↗
PubMed1996

Tracheal ligation does not correct the surfactant deficiency associated with congenital diaphragmatic hernia.

INTRODUCTION: Experimental tracheal ligation (CDH + TL) has been shown to reverse the profound lung hypoplasia associated with congenital diaphragmatic hernia (CDH) and to normalize gas exchange. The aim of this study was to determine whether this experimental therapy would correct the surfactant deficiency present in the fetal lamb model of CDH. METHODS: The CDH lamb model was created at 80 days' gestation, and tracheal ligation was performed at 110 days. At term, the lambs were delivered and were ventilated for 30 minutes. The lambs were killed, a pressure-volume curve performed, and the lungs lavaged to measure total phospholipid content. Finally, type II pneumocytes were isolated, and surfactant synthesis was assessed by the incorporation of tritiated choline into phosphatidylcholine. RESULTS: CDH + TL resulted in a lung significantly larger than that of CDH alone. The lungs of the former also had better oxygenation and ventilation. However, lung compliance was reduced compared with controls. Total alveolar phospholipid was dramatically lower, with a decrease in the proportion of phosphatidylcholine present. Surfactant synthesis by the isolated type II pneumocyte was significantly impaired. CONCLUSION: Occlusion of the fetal trachea produces a lung comparable in size to a normal control lung. However, broncheoalveolar lavage analysis shows a marked reduction in total phospholipid, with a decrease in surfactant synthesis by the type II pneumocyte. The normalization of gas exchange reported for this animal model may be only a transient phenomenon. Further studies are required to assess the impact of this surfactant deficiency on long-term lung function.

Animals↗
PubMed1996

Cisplatin and taxol activate different signal pathways regulating cellular injury-induced expression of GADD153.

Signal transduction pathways activated by injury play a central role in coordinating the cellular responses that determine whether a cell survives or dies. GADD153 expression increases markedly in response to some types of cellular injury and the product of this gene causes cell cycle arrest. Using induction of GADD153 as a model, we have investigated the activation of the cellular injury response after treatment with taxol and cisplatin (cDDP). Activation of the GADD153 promoter coupled to the luciferase gene and transfected into human ovarian carcinoma 2008 cells correlated well with the increase in endogenous GADD153 mRNA after treatment with taxol but not after treatment with cDDP. Following treatment with cDDP, the increase in endogenous GADD153 mRNA was 10-fold greater than the increase in GADD153 promoter activity. Likewise, at equitoxic levels of exposure (IC80), cDDP produced a 5-fold greater increase in endogenous GADD153 mRNA than taxol. The tyrosine kinase inhibitor tyrophostin B46 had no significant effect on the ability of taxol to activate the GADD153 promoter, but inhibited activation of the GADD153 promoter by cDDP in a concentration-dependent manner. Tyrphostin B46 synergistically enhanced the cytotoxicity of cisplatin; however, the same exposure had no significant effect on the cytotoxicity of taxol. We conclude that (1) taxol and cDDP activate GADD153 promoter activity through different mechanisms; (2) the signal transduction pathway mediating induction by cDDP involves a tyrosine kinase inhibitable by tyrphostin B46; and (3) that inhibition of this signal transduction pathway by tyrphostin synergistically enhances cDDP toxicity.

Antineoplastic Agents↗
PubMed1996

Expression of functional Porphyromonas gingivalis fimbrillin polypeptide domains on the surface of Streptococcus gordonii.

Genetically engineering bacteria to express surface proteins which can antagonize the colonization of other microorganisms is a promising strategy for altering bacterial environments. The fimbriae of Porphyromonas gingivalis play an important role in the pathogenesis of periodontal diseases. A structural subunit of the P. gingivalis fimbriae, fimbrillin, has been shown to be an important virulence factor, which likely promotes adherence of the bacterium to saliva-coated oral surfaces and induces host responses. Immunization of gnotobiotic rats with synthetic peptides based on the predicted amino acid sequence of fimbrillin has also been shown to elicit a specific immune response and protection against P. gingivalis-associated periodontal destruction. In this study we engineered the human oral commensal organism Streptococcus gordonii to surface express subdomains of the fimbrillin polypeptide fused to the anchor region of streptococcal M6 protein. The resulting recombinant S. gordonii strains expressing P. gingivalis fimbrillin bound saliva-coated hydroxyapatite in a concentration-dependent manner and inhibited binding of P. gingivalis to saliva-coated hydroxyapatite. Moreover, the recombinant S. gordonii strains were capable of eliciting a P. gingivalis fimbrillin-specific immune response in rabbits. These results show that functional and immunologically reactive P. gingivalis fimbrillin polypeptides can be expressed on the surface of S. gordonii. The recombinant fimbrillin-expressing S. gordonii strains may provide an effective vaccine or a vehicle for replacement therapy against P. gingivalis. These experiments demonstrated the feasibility of expressing biologically active agents (antigens or adhesin molecules) by genetically engineered streptococci. Such genetically engineered organisms can be utilized to modulate the microenvironment of the oral cavity.

Animals↗
PubMed1996

Structural domains of Porphyromonas gingivalis recombinant fimbrillin that mediate binding to salivary proline-rich protein and statherin.

Fimbriae (the oligomeric form of fimbrillin) are considered important in the adherence and colonization of Porphyromonas gingivalis in the oral cavity. In the present study, we have identified the structural domains of P. gingivalis fimbrillin that mediate the binding to salivary proline-rich protein 1 (PRP1) and statherin. A series of synthetic fimbrillin peptides were used to localize the active fimbrillin domains involved in the binding to PRP1 and statherin. The binding of 125I-labeled 41-r-Fim (whole-length recombinant fimbrillin, amino acid [aa] residues 1 to 337) to PRP1-coated hydroxyapatite beads (HAP) was strongly inhibited by the fimbrillin C-terminal peptides corresponding to aa residues 266 to 286 and 318 to 337 (peptides 266-286, and 318-337, respectively), while the binding to statherin was inhibited by C-terminal peptides 266-286, 293-306 and 307-326. Peptide 126-146 also showed a weak inhibitory effect, about half that of other active peptides, on the binding to both PRP1 and statherin. P. gingivalis whole-cell binding to PRP1- or statherin-coated HAP was inhibited by more than 80% by the same active peptides. To confirm that the C-terminal portion of fimbrillin includes domains responsible for the binding, two C-terminally truncated variants of recombinant fimbrillin were generated and purified. These were designated 34.5-r-Fim, corresponding to aa residues 1 to 286, and 32-r-Fim, corresponding to aa residues 1 to 265. 125I-34.5-r-Fim revealed 35 and 34% loss of binding ability to PRP1 and statherin, respectively. 125I-32-r-Fim had significantly less binding ability to PRP1 and statherin than 125I-34.5-r-Fim, which was reduced 78 and 73%, respectively. Whole-cell binding to PRP1-, statherin-, or whole saliva-coated HAP was inhibited up to 100% by 41-r-Fim, while 32-r-Fim also showed considerable inhibition, possibly due to the region of aa 126 to 146. Collectively, these results suggest that there are separate and multiple binding sites for PRP1 and statherin in the P. gingivalis fimbrillin, and the combination of all of these binding sites may be indispensable in establishing stable bacterial adherence to saliva-coated surfaces in the oral cavity.

Amino Acid Sequence↗
PubMed1996

Effect of high-altitude hypoxia on feeding responses and hedonic matrix in rats.

Albino male rats (n = 78) were exposed to a simulated high altitude (HA) equivalent to 7,620 m for 6 h daily, contiguously for a period of 21 days, to study their feeding behavior and gustatory responses. Their food, water intake, and body weight were recorded daily, and blood sugar and blood insulin were estimated once a week. All the parameters were recorded for a period of 3 wk each before, during, and after exposure to simulated HA. The results show a decrease in daily food and water intakes and body weight and mild hyperglycemia and hyperinsulinemia during hypoxic exposure. The 1-h single-bottle taste solution test showed a preference for sweet solutions (13% glucose and 0.2% saccharine) over citric acid (0.16%), sodium chloride (0.9%), and quinine sulfate (0.001%) during exposure to simulated HA. The 1-h two-bottle test containing glucose (calories plus taste) and saccharine (taste but no calories) administration showed a preference for the glucose solution over the saccharine solution. The trend of the 1-h intake of all test solutions also showed a reversal to preexposure levels after termination of HA hypoxia. It would appear that high-altitude stress influences food intake in a manner that sensory cues (e.g., preference for sweet substances) become more important.

Altitude↗
PubMed1996

Detection of excessive bronchoconstriction in asthma.

Airway hyperresponsiveness is easily assessed by measuring the concentration or dose of an inhaled agonist that produces a defined response, e.g., PC20 or PD20. However, this measure does not assess excessive bronchoconstriction. We report the results of analyzing bronchial dose-response curves by measuring percent fall in vital capacity (delta FVC%) as the response rather than the PC20. In our analysis, delta FVC% was measured at the PC20, and therefore it was the dependent variable, whereas the concentration of agonist was the independent variable, in contrast to the usual bronchoprovocation tests in which the response is the independent variable and the dose is the dependent variable. We reasoned that a dose-dependent increase in gas trapping with histamine would detect excessive bronchoconstriction as a decrease in FVC; in contrast, PC20 measures only the ease of bronchoconstriction. In 10 patients with mild asthma the reproducibility of delta FVC% when FEV1 fell by 20%, i.e., at the PC20 concentration of histamine, taken from a greater than 6-s FVC on an otherwise standard histamine challenge test was comparable to that of PC20. In 10 healthy asymptomatic subjects there were only trivial falls (0.3%) in FVC to as much as 16 mg/ml histamine. In a retrospective study of 146 patients with mild asthma, the delta FVC% was normally distributed (13.2 +/- 5.5 SD%) and did not correlate with the number of beta 2-agonist prescriptions or the PC20, but it did correlate with the number of prescriptions written per month for oral prednisone (r = 0.55, p < 0.02). We conclude that delta FVC% when FEV1 falls by 20% is a safe method of detecting excessive bronchoconstriction, and it reveals that different asthmatics react in fundamentally different ways to the same agonist. This may be useful in detecting the asthmatic at risk for serious disease.

Adult↗
PubMed1996

Use of ethnographic methods for applied research on diabetes among the Ojibway-Cree in northern Ontario.

This article presents the results of applied ethnographic research aimed at developing a community-based diabetes prevention program in an isolated Ojibway-Cree community in northern Ontario. Using qualitative techniques, the authors describe diabetes in its sociocultural context and underlying belief systems that affect related activity and dietary behaviors. Local concepts of food and illness are dichotomized into "Indian" and "white man's" groupings, with Indian foods perceived as healthy and white man's foods felt to be unhealthy. Diabetes is believed to result from consumption of white man's "junk foods" (sugar, soda); some believe the disease can be avoided by eating traditional Indian foods such as game animals (moose, beaver, duck). While dietary linkages to diabetes are recognized, physical activity as a means of controlling obesity and decreasing the risk for diabetes is not part of the local ethnomedical model. This information is being used to develop culturally appropriate health education interventions.

Adolescent↗
PubMed1996

Parent and sibling influences on adolescent alcohol use and misuse: evidence from a U.S. adoption cohort.

OBJECTIVE: Although adolescent alcohol use has been consistently associated with parental drinking behavior, sibling drinking behavior and family functioning, the extent to which these associations owe to genetic or shared environmental influences has not been previously investigated. Using an adoption study design, we sought to determine whether the familial correlates of adolescent alcohol involvement were due to common genetic or common environmental effects. METHOD: The sample consisted of 653 adopted families ascertained through adoption agencies in four U.S. states. Each family consisted of a target adopted adolescent, an adoptive mother and an adoptive father. In addition, 68 birth adolescents (i.e., biological offspring of the adoptive parents) and 187 second adopted adolescents from these families participated in the study. All participants completed a mail survey that included assessment of drinking behavior and family functioning. RESULTS: The relationship between parental problem drinking and adolescent alcohol involvement was moderate and significant among birth offspring (corrected multiple correlation, Rc = .30), but small and non-significant among adoptive offspring (Rc = .00). The relationship between adolescent alcohol involvement and family functioning was substantial for birth offspring (Rc = .39), but only modest for adoptive offspring (Rc = .16). The nonbiological sibling correlation for involvement with alcohol was significant (r = .24) and moderated by sibling pair demographic similarity, such that same-sex, similar-age siblings were substantially more similar (r = .45) than opposite-sex, dissimilar-aged siblings (r = .01). CONCLUSIONS: These findings suggest that adolescent alcohol use is affected minimally by the environmental consequences of parent problem drinking and family functioning, but substantially by sibling environmental effects.

Adolescent↗
PubMed1996

Developmental neurotoxicity of methanol exposure by inhalation in rats.

The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concerns about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult rats following perinatal exposure to methanol vapor. Four cohorts of pregnant Long-Evans hooded rats, each cohort consisting of an exposure and a control group, were exposed to 0 parts per million (ppm) (control) or 4,500 ppm methanol vapor for six hours daily beginning on gestation day (GD) 6 with dams and pups then being exposed postnatal day (PND) 21. Exposures took place in 2-m3 Rochester-type inhalation chambers while the animals remained in their plastic breeder cages. Prenatal and postnatal blood methanol concentrations were determined by gas chromatography. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 micrograms/mL throughout gestation and lactation. Average blood methanol concentrations of the pups were about twice those of the dams. Because such results appeared consistently across the other cohorts, we decided to obtain additional data with Cohort 4. Once it had undergone the standard exposure protocol, we selected sets of extra pups from those that had not been assigned previously to the adult phase of behavioral testing. Each set was exposed once, at ages that extended out to PND 52, for one additional six-hour session of exposure to 4,500 ppm methanol. The blood methanol concentrations of these pups declined until about PND 48, at which time they approximated those of the dams. These findings might be accounted for by a process of metabolic maturation in the pups that remains to be identified.

Animals↗
PubMed1996

Unmonitored apexification of wide open apex in nonvital, immature incisor: a case report.

Apexification is the accepted procedure to form an apical stop in nonvital teeth with incomplete root formation. A case is presented in which apexification with calcium hydroxide was performed on erupting maxillary central incisor in 7-year-old female child with immature root (half root) formation and wide open apex. Although it was an induced procedure, but unmonitored. Patient did not return until 18 months after his first visit. Treatment then concluded with gutta percha obturation against firm "cap shaped" apical stop.

Calcium Hydroxide↗
PubMed1996

Training of opinion leaders in family planning in India: does it serve any purpose?

Community leaders are known to play a crucial role in the diffusion of innovations. The government of India started an ambitious programme for the training of opinion leaders in family planning, so as to provide a boost to its National Family Planning (Welfare) Programme. The present study attempts to analyse the knowledge, attitudes and practices of opinion leaders who had been trained in such Orientation Training Camps, vis a vis their untrained counterparts from the same geopolitical region. There was a highly significant difference between the knowledge of the two groups (p < 0.001) and a minor difference in their attitudes towards family planning (p = 0.18), but the practices of opinion leaders from both the groups were identical, thus pointing to a significant KAP-gap in the trained group. Opinion leaders from both the groups were engaged in minimal or negligible motivational work among their followers for acceptance of contraception, and only a very limited few from both the groups had themselves adopted any method of modern contraception.

Community Health Workers↗
PubMed1996

Skeletal muscle growth of oMTla-oGH transgenic mice.

Forty-eight transgenic mice carrying an ovine metallothionein 1a-ovine growth hormone (oMTla-oGH) transgene and 48 littermate control mice were used to investigate the effect of GH transgene on the growth and biochemical characteristics of skeletal muscle. Transgene expression was initiated in the transgenic mice by the addition of zinc sulfate to the water at 21 d of age; control mice were also supplemented with zinc sulfate. These mice were maintained on zinc sulfate until 84 d of age. Groups of mice (16 controls, 16 transgenics) were killed at 21, 42 and 84 d of age and muscles from the hind leg were dissected, weighed and analyzed. At 84 d, male transgenics were 32% heavier than controls, while female transgenics were 47% heavier. Transgenic mice of both sexes had smaller (p < 0.01) muscles than controls at weaning (21 d). In spite of significantly heavier body weights of transgenic mice at 84 d of age, there were no significant differences in muscle weights. This was due to a significantly lower (p < 0.01) proportion of muscle, expressed as percentages of body weights, in transgenic mice compared with controls. Higher DNA and RNA concentrations at 42 d of age and elevated cathepsins C and H activities at 42 and 84 d of age indicate that muscle protein metabolism is more active in transgenic mice, which are growing at a greater rate than controls from weaning to 84 d of age. The fact that oMTla-oGH transgenic mice inherently have a lower proportion of muscle, compared to controls and that this proportion does not change in spite of transgene activation and 30 fold increase in plasma GH levels, suggests the hypothesis that muscle growth may be controlled by locally produced IGFs, which are essentially independent of circulating GH concentrations.

Animals↗
PubMed1996

Production of extracellular proteases and amylases by some acidophilic and alkalophilic bacteria.

Twelve bacteria were isolated from two effluent sources of Shaw-Wallace Gelatins, Jabalpur. Six bacteria from dicalcium phosphate plant effluent (pH-5) and six from main drain of the factory (pH-10) were isolated. Two facultatively acidophilic and two facultatively alkalophilic bacteria were selected and tentatively identified as Plesiomonas shigelloides, Aeromonas hydrophilla, Klebsiella pneumoniae and Staphylococcus saprophyticus respectively. Acidic amylases were produced in higher amounts on 4th day of incubation by Plesiomonas shigelloides and on 6th day by Aeromonas hydrophilla. Alkaline amylases were produced in higher amounts on 4th day of incubation by Klebsiella pneumoniae and on 8th day by Staphylococcus saprophyticus in vitro.

Aeromonas↗