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Biomedical subjects

Puneet Sharma

Publications and source records attributed to Puneet Sharma.

11 recordsLinked to original sources

Comparison of clock gene expression in SCN, retina, heart, and liver of mice.

In mammals, the suprachiasmatic nuclei (SCN) in the hypothalamus are the site of a central circadian pacemaker, regulating overt rhythms of behaviour and coordinating the rhythmic activity of oscillators in peripheral tissues. Circadian rhythms in all tissues appear to arise from interacting transcriptional-translational feedback loops, involving a core set of clock genes. Whilst it seems likely that there will be broadly similar mechanisms between the central and peripheral oscillators, the extent to which the fine details of gene expression are conserved between different organs has yet to be assessed. In this study, we examine the molecular profile of clock genes within the central SCN pacemaker and peripheral oscillators, identifying differences in phasing, amplitude, waveform, and basal expression levels.

Animals↗

Effect of Gd-DTPA-BMA on blood and myocardial T1 at 1.5T and 3T in humans.

PURPOSE: To compare T(1) values of blood and myocardium at 1.5T and 3T before and after administration of Gd-DTPA-BMA in normal volunteers, and to evaluate the distribution of contrast media between myocardium and blood during steady state. MATERIALS AND METHODS: Ten normal subjects were imaged with either 0.1 mmol/kg (N = 5) or 0.2 mmol/kg (N = 5) of Gd-DTPA-BMA contrast agent at 1.5T and 3T. T(1) measurements of blood and myocardium were performed prior to contrast injection and every five minutes for 35 minutes following contrast injection at both field strengths. Measurements of biodistribution were calculated from the ratio of DeltaR(1) (DeltaR(1myo)/DeltaR(1blood)). RESULTS: Precontrast blood T(1) values (mean +/- SD, N = 10) did not significantly differ between 1.5T and 3T (1.58 +/- .13 sec, and 1.66 +/- .06 sec, respectively; P > 0.05), but myocardium T(1) values were significantly different (1.07 +/- .03 sec and 1.22 +/- .07 sec, respectively; P < 0.05). The field-dependent difference in myocardium T(1) postinjection (T(1)@3T - T(1)@1.5T) decreased by approximately 72% relative to precontrast T(1) values, while the field-dependent difference of blood T(1) decreased only 30% postcontrast. Measurements of DeltaR(1myo)/DeltaR(1blood) were constant for 35 minutes postcontrast, but changed between 1.5T and 3T (0.46 +/- .06 vs. 0.54 +/- .06, P < 0.10). CONCLUSION: T(1) is significantly longer for myocardium (but not blood) at 3T compared to 1.5T. The differences in T(1) due to field strength are reduced following contrast administration, which may be attributed to changes in DeltaR(1myo)/DeltaR(1blood) with field strength.

Adult↗

Many-body correlations versus mode-coupling effects in the dynamics of dense gases.

Time dependent contributions due to the triplet and quadruplet correlation functions have been combined with microscopically determined contribution due to the pair correlation function for the transverse stress correlation function. Comparison of the results with simulation data shows that contributions due to two- and three-body static correlation functions are sufficient to understand the viscous dynamics of dense gases. However, close to the triple point, it becomes necessary to include the contribution due to the four-body correlation function. The contribution due to the mode coupling effect has been contrasted with the contribution due to three- and four-body correlation functions. It is noted that the mode coupling contribution plays a similar role as that due to many-body correlation functions.

Journal Article↗

Transdermal delivery of naloxone: skin permeation, pharmacokinetic, irritancy and stability studies.

The current investigation aims to evaluate ex vivo, in vivo performance, stability and irritancy potential of a transdermal formulation of naloxone (NLX) developed at our laboratory at different concentrations (10, 20 and 30mg/g of gel) in a transdermal reservoir patch. Ex vivo permeation studies were performed by employing porcine and rat skins. In vivo performance was assessed in Sprague-Dawley rats by single and multiple application of the patch. Further stability of the formulation was established for 3 months at accelerated stability conditions as per ICH guidelines. Amongst the barriers used the rat skin was found to be more permeable than the porcine epidermis and the flux across each barrier increased with increasing thermodynamic activity of drug in the gel. Based on ex vivo data, the surface area (SA) of the patch was predicted to be 39.6 cm(2) in order to achieve therapeutic blood levels. Upon single dose administration, the steady-state levels were maintained from 4-48 h, which proves the clear advantage of transdermal delivery system over the current mode of administration, i.e., intravenous (i.v.) bolus which is effective upto a maximum of 1.5h. Upon multiple dose administration, the sustained steady state for 12h, even after patch removal proves the formation of drug depot in the skin. The formulations were found to be stable with respect to NLX assay and penetration enhancer efficacy upto 3 months under accelerated stability conditions. The alteration of penetration barrier function, as evidenced by increased trans epidermal water loss (TEWL) was not accompanied by any significant amount of skin irritation measured using laser doppler velocimetry (LDV). The developed transdermal delivery system of NLX is efficacious, stable and safe upon single and multiple dose applications each lasting for 48 h.

Administration, Cutaneous↗

An indigenous spacer device for drug delivery in severely dyspnoeic patients.

Bronchodilator aerosols are commonly delivered through nebulizers or metered dose inhalers (MDI) to treat bronchospasm. Although the clinical results obtained with both these devices are comparable, the use of MDI offers several advantages like lower drug dose, reduced risk of complications, reliability of dosing, ease of administration, less personnel time and reduced cost. However, in non-intubated, spontaneously breathing patients, the amount of drug inhaled depends on the coordination of the inspiratory phase and delivery of the drug. In severely dyspnoeic or disoriented patients in the casualty department or intensive care settings, this is often not possible. Valved spacers and breath-actuated inhalers may not be easily available in such situations. Also, the spacer devices cannot be connected to the anatomical facemask and the need to discontinue oxygenation for aerosol delivery further limits their use.

Bronchial Spasm↗

Role of many-body correlations in dynamics of liquids.

A time correlation function is written exactly in terms of infinite series with each term containing contributions separately due to two, three, and higher body static correlations. For a time correlation function of force acting on a tagged particle, it is found that contributions due to two and three body static correlation functions are sufficient to understand dynamics of dense gases whereas at the triple point and in the glassy phase it is necessary to include contributions due to a four body correlation function.

Journal Article↗

Comparisons of mortality and pre-discharge respiratory outcomes in small-for-gestational-age and appropriate-for-gestational-age premature infants.

BACKGROUND: There are differences in the literature regarding outcomes of premature small-for-gestational-age (SGA) and appropriate-for gestational-age (AGA) infants, possibly due to failure to take into account gestational age at birth. OBJECTIVE: To compare mortality and respiratory morbidity of SGA and AGA premature newborn infants. DESIGN/METHODS: A retrospective study was done of the 2,487 infants born without congenital anomalies at </=36 weeks of gestation and admitted to the neonatal intensive care unit (NICU) at John Dempsey Hospital, between Jan. 1992 and Dec. 1999. Recent (1994-96) U.S. birth weight percentiles for gestational age (GA), race and gender were used to classify neonates as SGA (<10th percentile for GA) or AGA (10th-90th percentile for GA). Using multivariate logistic regression and survival analyses to control for GA, SGA and AGA infants were compared for mortality and respiratory morbidity. RESULTS: Controlling for GA, premature SGA infants were at a higher risk for mortality (Odds ratio 3.1, P = 0.001) and at lower risk of respiratory distress syndrome (OR = 0.71, p = 0.02) than AGA infants. However multivariate logistic regression modeling found that the odds of having respiratory distress syndrome (RDS) varied between SGA and AGA infants by GA. There was no change in RDS risk in SGA infants at GA </= 32 wk (OR = 1.27, 95% CI 0.32 - 1.98) but significantly decreased risk for RDS at GA > 32 wk (OR = 0.41, 95% CI 0.27 - 0.63; p < 0.01). After controlling for GA, SGA infants were observed to be at a significantly higher risk for developing chronic lung disease as compared to AGA infants (OR = 2.2, 95% CI = 1.2 - 3.9, P = 0.01). There was no significant difference between SGA and AGA infants in total days on ventilator. Among infants who survived, mean length of hospital stay was significantly higher in SGA infants born between 26-36 wks GA than AGA infants. CONCLUSIONS: Premature SGA infants have significantly higher mortality, significantly higher risk of developing chronic lung disease and longer hospital stay as compared to premature AGA infants. Even the reduced risk of RDS in infants born at >/=32 wk GA, (conferred possibly by intra-uterine stress leading to accelerated lung maturation) appears to be of transient effect and is counterbalanced by adverse effects of poor intrauterine growth on long term pulmonary outcomes such as chronic lung disease.

Chronic Disease↗

RP-HPLC method and its validation for the determination of naloxone from a novel transdermal formulation.

The aim of the present work was to develop a simple and reliable liquid chromatographic method for the quantitative determination of naloxone (NLX) in a novel transdermal formulation. Chromatography was carried out by reversed-phase technique on a C-18 column with a mobile phase composed of methanol, acetonitrile and 50 mM phosphate buffer (pH 7) in the proportion of 40:20:40 v/v/v, at a flow rate of 1 ml/min. The UV spectrophotometric determination was performed at 220 nm. This method was found to be specific and accurate with the mean recovery of 98.72% in the range of 2-50 microg/ml, and a run time of 15 min (retention time of NLX 11.3 min). Method was applied for stability testing of novel transdermal formulation developed in our laboratory. Assay content of NLX in the formulation was determined in stability samples and compared with the control samples. Statistical analysis by Student's t-test showed no significant difference between the assay content of NLX in control and test samples at 95% confidence interval. Overall, the proposed method is highly sensitive, precise and accurate and can be used for the reliable quantitation of NLX in developed transdermal formulation with the added advantage of simple procedure.

Administration, Cutaneous↗

Binary and multiparticle contributions to the velocity autocorrelation function.

A method for including the contribution of many-body correlation effects to the microscopically obtained results of the two-body contribution to the velocity autocorrelation has been proposed. A significant improvement over the results obtained through only binary contribution has been found, as can be judged by comparing the results for force and velocity autocorrelation functions of Lennard Jones fluids with that of molecular dynamic simulations. The agreement of results of self-diffusion coefficient is also quite good with simulation data over a wide range of densities and temperatures.

Journal Article↗

Subdural block complicating spinal anesthesia?

IMPLICATIONS: Features suggestive of subdural block appeared after an apparently normal subarachnoid block. The long bevel of the reusable Quincke-type spinal needle may have contributed to the development of this complication. We propose that spinal needles should have a smaller bevel to minimize the possibility of such a complication.

Anesthesia, Spinal↗