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Biomedical subjects

V Srinivasan

Publications and source records attributed to V Srinivasan.

At least 73 records · Page 4Linked to original sources

Comparative analysis of the regions binding beta gamma-subunits in Galpha and PH domains.

Some of the pleckstrin homology (PH) domains are shown to bind beta gamma-subunits of a G-protein. In this paper we present a detailed comparison of sequences and structural features of beta gamma-binding regions in PH domains and alpha-subunits (G alpha) of known structure. Our comparison involves switch II region in G alpha and a C-terminal region of PH domain structures and we suggest a similarity in these regions. By comparing the active and inactive forms of G alpha structures we predict that some of the bulky hydrophobic residues in switch II region might interact with beta gamma-subunits. Subsequent to completion of this work we find that this prediction is absolutely consistent with recently reported crystal structures of heterotrimeric G-proteins. We discuss the feasibility of common principles in the recognition G alpha and PH domains by beta gamma-subunits.

Amino Acid Sequence↗

Correlation of in vivo topical efficacies with in vitro predictions using acyclovir formulations in the treatment of cutaneous HSV-1 infections in hairless mice: an evaluation of the predictive value of the C* concept.

The purpose of this study was to carry out an extensive examination of the C* concept for prediction of the topical antiviral efficacies of acyclovir (ACV) formulations in a hairless mouse model for the treatment of cutaneous herpes simplex virus type-1 (HSV-1) infections. This method is based on estimation of the free drug concentration at the target site (C*), which is presumed to be the basal cell layer of the epidermis. Five different formulations (containing 5% ACV) were examined in a finite dose multiple dosing regimen (twice a day application) to simulate the clinical situation. For determination of C*, in vitro ACV fluxes across the hairless mouse skin were measured in an in vivo-in vitro experimental design that approximated the in vivo antiviral treatment protocol. Then, the in vivo antiviral efficacies were measured using a 1-day delayed (after HSV-1 virus inoculation) 4-day treatment protocol. 10 microL/cm2 dose of ACV formulation was applied every 12 h for 4 days after which the lesions were scored and efficacies were calculated. Our results indicate that, over a wide range of efficacies, the predictions based on C* (estimated from the experimental fluxes) are in good agreement with the in vivo antiviral efficacies. These studies, therefore, support the validity of the C* concept for various ACV formulations and suggest that the C* approach has potential for future practical situations.

Acyclovir↗

Lipoma of the parotid gland presenting with facial palsy.

Facial palsy in the presence of ipsilateral parotid tumour is considered to be pathognomonic of malignancy. However, benign neoplasms and inflammatory lesions of the parotid gland have been reported to present with facial palsy. A case of lipoma of the parotid gland associated with partial facial paralysis is reported. Lipomas are very rarely seen in this site. To our knowledge, a lipoma of the parotid producing facial paralysis has not been described previously. This report highlights the difficulties in pre-operative diagnosis and management of such a lesion.

Facial Paralysis↗

Quantitative description of the effect of molecular size upon electroosmotic flux enhancement during iontophoresis for a synthetic membrane and human epidermal membrane.

This study focused upon quantitatively determining the influence of permeant molecular size upon flux enhancement which results from electroosmosis. The first phase of the study involved validation of a fundamental model describing the molecular size dependence of flux enhancement which results from convective solvent flow. This was accomplished using a model synthetic membrane (stack of 50 Nuclepore membranes) and four model permeants with a molecular weight range of 60-504 (urea, mannitol, sucrose, and raffinose). The steady-state flux of each permeant was determined under passive conditions and applied voltages of 125, 250, 500, and 1000 mV using side-by-side diffusion cells and a four-electrode potentiostat system. On the basis of the permeability enhancement for each permeant at each applied voltage (relative to the passive permeability) it was possible to calculate the effective solvent flow velocity from each permeant at each field strength. An important finding was that the flux enhancement due to electroosmosis was strongly molecular weight dependent (i.e., the flux enhancement ratio was around 4 times greater for raffinose than for urea, with mannitol and sucrose yielding intermediate values), while the calculated effective flow velocity at each voltage was independent of the molecular weight of the permeant. This coupled with a linear correlation between flow velocity and applied voltage served to establish the validity of the method and model. The second phase of the study was an extension of the model to human epidermal membrane (HEM). These experiments involved simultaneously measuring the fluxes of [14C]urea and [3H]sucrose across HEM samples under passive, 250 mV, and 500 mV conditions. Similar to the Nuclepore system, the observed flux enhancement ratios with HEM were approximately 3 times greater for sucrose than for urea. A detailed analysis of the HEM data showed semiquantitative agreement between predictions of the model and experimental results.

Electricity↗

Analgesic and immunomodulatory effects of codeine and codeine 6-glucuronide.

PURPOSE: The antinociceptive and immunosuppressive effects of codeine and codeine 6-glucuronide were determined in rats after intracerebroventricular administration. METHODS: Codeine 6-glucuronide was synthesized using a modification of the Koenigs-Knorr reaction. A lipophilic intermediate formed during synthesis, methyl [codein-6-yl-2,3,4-tri-O-acetyl-beta-D-glucopyranosid] uronate, was also tested. Morphine was used as a positive control to compare antinociceptive potencies of these compounds. RESULTS: All compounds tested produced significant analgesic responses, as assessed by the tail flick model. Additionally, codeine 6-glucuronide showed significantly less immunosuppressive effects than codeine in vitro. CONCLUSIONS: We conclude that codeine 6-glucuronide and related compounds may have clinical benefit in the treatment of pain in immune compromised patients.

Adjuvants, Immunologic↗

The U.S. Pharmacopeia's role in establishing public standards for aerosols.

USP, a non-governmental and not-for-profit organization, establishes public standards for and information on articles used in the healing art through an elected body of Committee of Revision comprised of scientific experts in the fields of medicine, pharmacy, pharmaceutical chemistry, analytical chemistry, and others. To be consistent with latest developments in manufacturing and analytical technologies, USP has a continuous revision policy. Major revisions to the General Chapter on Aerosols officially adopted recently that include detailed descriptions of multi-stage cascade impactor apparatus, two different single-stage impaction devises used in particle size of determination, uniformity of assage units, minimum fill and other tests are discussed. Further revisions to the chapter on Aerosols under consideration such as test procedure for nebulizers, extractables and particulate matter are discussed.

Administration, Inhalation↗

Comparative evaluation of cine-esophagogram with esophageal manometry in assessing esophageal motility in progressive systemic sclerosis.

BACKGROUND: Esophageal manometry is considered the gold standard in the diagnosis of esophageal motility disorders. Cine-esophagogram using barium is also a good investigation to screen patients for motor disorders of the esophagus. Comparison between these two investigations has not often been reported in patients with progressive systemic sclerosis (PSS). AIM: To determine relative merits of cine-esophagogram and esophageal manometry in detecting esophageal motor dysfunction in PSS patients. METHODS: Thirty-five patients with PSS irrespective of esophageal symptoms underwent esophageal manometry and cine-esophagogram, results and their were compared. RESULTS: Sensitivity and specificity of cine-esophagogram as compared to manometry were 96.1% (95% CI 88.7%-100%) and 55.5% (95% CI 23%-87.9%) respectively. Its positive predictive value was 86%. CONCLUSION: While esophageal manometry can identify esophageal motor disorder in PSS, cine-esophagogram can be resorted to in doubtful situations, for confirmation of diagnosis.

Adolescent↗

Influence of respiration on human sympathetic skin response.

Sympathetic skin response (SSR) is a reflexly elicited potential of the sweat glands, the afferent and efferent fibres of the reflex are cutaneous sensory fibres (if the SSR is elicited by electrical stimulus) and sympathetic sudomotor fibres respectively. Our earlier study indicated that latency, besides duration and amplitude, of SSR of a given normal individual showed significant variations between many trials of stimulation, even in a single sitting. Since deep inspiration is also an effective stimulus to elicite SSR, the present study was conducted to assess the influence of respiration on SSR. Thirty-four healthy students participated in the study. The skin of the forearm of the dominant hand was stimulated by electrical square pulse and SSR was recorded from the ipsilateral hand. SSR was elicited and recorded in each subject during the various phases of respiration, namely, end expiration (EE), end inspiration (EI), mid expiration (ME) and mid inspiration (MI). It was observed that the mean values of SSR latency during these respiratory phases (EE : 1.59, EI: 1.51, ME : 1.55, and MI: 1.56 sec) were similar, indicating that the normal respiration might not be responsible for the observed interstimulation variations in latency in any given individual.

Adolescent↗

Day-case septal surgery under general anaesthesia and local anaesthesia with sedation.

Septal surgery (submucous resection and septoplasty) has been performed as a day-case procedure routinely under general anaesthesia and local anaesthesia with sedation at the Ipswich Hospital since 1992. The outcome of the day-case septal surgery over a period of 18 months has been audited. A total of 95 cases were operated on of which 48 were under general anaesthesia (GA) and 47 under local anaesthesia (LA) with sedation using midazolam intravenously. The bleeding rate and overnight admission rate were 10.5 and 11.4 per cent respectively. The bleeding rate was the same in both GA and LA groups. The combination of local anaesthesia and sedation has been found to be safe, effective and acceptable to patients. It is concluded that septal surgery is suitable as a day procedure and that local anaesthesia combined with sedation has a definite place if carried out properly.

Adolescent↗

Dynamic simulation of the laboratory-scale controlled ecological life support system.

There are a number of design and control issues that need to be resolved in order to make a crop growth chamber an integral part of a controlled ecological life support system (CELSS) capable of supporting life on extended space missions. A modeling and simulation effort, along with the construction of an experimental testbed, are underway at NASA Ames Research Center to explore the long-term dynamic behavior of closed-loop life support systems. One problem that has been isolated for investigation is the stability and robustness of closed-loop systems over extended periods of time. Currently a crop growth chamber is being integrated with a solid waste processor to study closure of the carbon loop. A dynamic simulation model of the system was developed to evaluate system design options and operational alternatives. The model was also used to simulate the impact of system buffer size on the dynamic behavior of conditions inside the crop growth chamber.

Biomass↗

Randomised controlled field trial of two antenatal care packages in rural south India.

A randomised community intervention trial was undertaken in 12 subcentres in Karur health unit district, Tamil Nadu, to compare the efficacy of two antenatal care packages. A newly recommended 'high-risk' strategy package and a uniform package recommended by the Tamil Nadu Government were each implemented in 4 randomly selected subcentres by the study team, and the latter was also delivered by routine health services in the 4 remaining subcentres. Analyses were based on 294 pregnant women on the high-risk package (HR), 242 on the Tamil Nadu Government (TNG) package and 335 women in the control series. The HR package reduced the differences between the high-risk women and the others in mean haemoglobin and the percentages with preventable neonatal morbidity and low birth weight, and consequently the overall outcome was better in the HR series than in the TNG series. Finally, the results with the TNG package were better when it was implemented by the study team than by the routine health services, in terms of preventable maternal morbidity and preventable perinatal morbidity, but there was no impact on birth weight.

Birth Weight↗

Quantitative in vivo iontophoretic studies.

An experimental methodology was developed to evaluate the physicochemical basis for in vitro-in vivo correlations in iontophoretic delivery situations. This experimental methodology can be used to quantitatively evaluate the extent of interaction between chemical permeation enhancers and iontophoresis for drug delivery. The inherent advantages of using Ag/AgCl electrodes are fully exploited to control pH and minimize depletion of permeant during prolonged periods of iontophoresis.

Animals↗

Massive intraperitoneal hemorrhage associated with renal pathology.

We report on 2 patients who presented with massive intraperitoneal hemorrhage. In spontaneous renal hemorrhage there is often an underlying pathological condition, usually renal carcinoma. The investigation of choice is computerized tomography, while arteriography is reserved for cases in which no renal mass is found. Nephrectomy may be life-saving but conservative treatment is an acceptable alternative when the underlying pathological condition is benign and the patient is in stable condition.

Aged↗