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Biomedical subjects

S Venkatesh

Publications and source records attributed to S Venkatesh.

At least 37 records · Page 2Linked to original sources

Brucellar epididymo-orchitis in Saudi Arabia: a retrospective study of 26 cases and review of the literature.

OBJECTIVE: To review the clinical and laboratory features and response to treatment of patients with acute brucellar epididymo-orchitis reporting to a tertiary care hospital in Riyadh, and to compare these with other cases reported previously. PATIENTS AND METHODS: In this retrospective study, records of all 26 adult patients with brucellosis, who presented with epididymitis or epididymo-orchitis at a tertiary hospital in Riyadh from 1983 to 2000, were reviewed. Positive blood culture or high agglutination titres of > or = 1 : 320 and positive clinical manifestations of brucellosis were the main criteria for diagnosing brucellosis. Among these cases, epididymitis or epididymo-orchitis was diagnosed on the basis of a typical history of gradual onset of scrotal pain and findings of enlarged tender testes and/or epididymis. RESULTS: Epididymo-orchitis occurred in 1.6% of all patients with brucellosis. Most (58%) were 25--44 years old; approximately 77% of the patients presented with acute symptoms of < 2 weeks' duration. All patients complained of swollen painful testicles. Other presenting symptoms included undulant fever (96%), chills (54%) and arthralgia (23%). Four patients had dysuria and one haematuria. Ten patients gave a positive history of ingestion of raw milk and milk products; one patient had laboratory-acquired brucellosis. Six patients had unilateral epididymo-orchitis (two with features of florid presentation); the remaining 20 had only orchitis (bilateral in two, right in 10 and left in eight). Leucocytosis was present in six patients; 25 had initial agglutination titres of > 1 : 320 and the remaining patient had a positive blood culture. All patients received combined therapy with streptomycin for the first 2 weeks (or oral rifampicin for 6 weeks) with doxycycline or tetracycline for 6 weeks. All showed improvement, fever subsided in 2--5 days and the scrotal enlargement and tenderness regressed. Only one patient had a relapse within one year. CONCLUSION: In brucellosis-endemic areas, clinicians encountering epididymo-orchitis should consider the likelihood of brucellosis. A careful history, a meticulous physical examination and a rapid laboratory evaluation help in diagnosis. Clinical and serological data are sufficient for diagnosis. Leucocytosis is not an atypical feature of brucellar epididymo-orchitis and so cannot be used for differentiating it from the nonspecific variety. Conservative management with combination antibiotic therapy is adequate for managing brucellar epididymo-orchitis.

Adolescent↗

Role of the development scientist in compound lead selection and optimization.

The R&D process for bringing drugs from discovery laboratories to the marketplace is undergoing rapid change, as enabled by new technologies and as demanded by the global pharmaceutical business environment. One consequence of the accelerated R&D paradigm is a blurring of the traditional discovery-development interface, which in turn impacts the traditional roles of discovery and development scientists. R&D organizations must find ways to screen out rapidly compounds that have relatively poor probability of successful registration. Quality of development candidates can be favorably influenced by early consideration of "developability" criteria along with receptor-based potency and specificity. Computational approaches and/or high-throughput experimental determinations will be used increasingly to profile compound characteristics which influence "developability." If such criteria are considered at the time of lead selection and optimization, the compound attrition rate during later development should be decreased from the historical norm. This article discusses the emerging role of development scientists during small-molecule lead selection and optimization. The changing role of development scientists also has implications for graduate curricula in the pharmaceutical sciences.

Chemistry, Pharmaceutical↗

How honeybees make grazing landings on flat surfaces.

Freely flying bees were filmed as they landed on a flat, horizontal surface, to investigate the underlying visuomotor control strategies. The results reveal that (1) landing bees approach the surface at a relatively shallow descent angle; (2) they tend to hold the angular velocity of the image of the surface constant as they approach it; and (3) the instantaneous speed of descent is proportional to the instantaneous forward speed. These characteristics reflect a surprisingly simple and effective strategy for achieving a smooth landing, by which the forward and descent speeds are automatically reduced as the surface is approached and are both close to zero at touchdown. No explicit knowledge of flight speed or height above the ground is necessary. A model of the control scheme is developed and its predictions are verified. It is also shown that, during landing, the bee decelerates continuously and in such a way as to keep the projected time to touchdown constant as the surface is approached. The feasibility of this landing strategy is demonstrated by implementation in a robotic gantry equipped with vision.

Animals↗

Antinociceptive and anti-inflammatory activity of Sida rhomboidea leaves.

Various organic extracts of Sida rhomboidea leaves were studied for antinociceptive and anti-inflammatory activity at a dose of 200 mg/kg. Ethyl acetate extract has shown significant (P < 0.01) antinociceptive activity. Percentage inhibition of edema by butanolic extract (33.05, P < 0.001) is comparable to that of phenylbutazone, 100 mg/kg inhibition (38.83%). Phytochemical screening of the extracts indicated the presence of alkaloids, steroids and/or triterpenoids and their glycosides, tannins, flavonoids and their glycosides, carbohydrates and absence of cardiac glycosides.

Analgesics↗

Epstein-Barr virus induced non-Hodgkin's lymphoma as a presenting manifestation of acquired immune deficiency syndrome.

A 30 year old, human immunodeficiency virus (HIV) positive patient presented with fever and intra-abdominal lymphadenopathy. Cytology smears from the nodes showed a high grade Non-Hodgkin's lymphoma (NHL) which was B cell in origin. NHL was the acquired immune deficiency syndrome (AIDS) defining disease in this patient. Polymerase chain reaction (PCR) studies on tumour tissue showed presence of Epstein Barr Virus.

Acquired Immunodeficiency Syndrome↗

Compositional heterogeneity in parenteral lipid emulsions after sedimentation field flow fractionation.

This study examines the size and compositional heterogeneity of particles in a commercial lipid emulsion (Intralipid) before and after equilibration with penclomedine, a highly lipophilic cytotoxic agent. Emulsions were fractionated by sedimentation field-flow fractionation (sedFFF), and particle sizes of the monodisperse fractions were determined by photon correlation spectroscopy. The triglyceride (TG), phosphatidylcholine (PC), and penclomedine (in drug loaded emulsions) contents in each fraction were determined by HPLC. The aqueous-entrapped volume within Intralipid was determined to be approximately 10% by size-exclusion chromatography using [3H]mannitol. Thirteen sedFFF fractions collected from the drug free emulsions yielded particles ranging in size from 154 to 423 nm. Total channel recoveries were 89% and 95% for TG and PC, respectively. Apparent particle densities varied significantly with size, suggesting heterogeneity in composition as confirmed by PC/TG mass ratios which varied dramatically. Computer fits of the distribution profiles suggested populations of phospholipid vesicles and oil droplets containing excess phospholipid in addition to classical emulsion droplets. Drug loading induced a significant shift of the predominant triglyceride containing population to a larger particle size. The penclomedine distribution profile closely mimicked that of the TG rather than the PC fraction. These studies suggest the need to consider not only size distribution but also compositional distribution in characterizing parenteral emulsions.

Antineoplastic Agents↗

Mechanisms of tubular sodium chloride transport.

Extracellular fluid volume is determined by sodium and its accompanying anions. There are control mechanisms which regulate sodium balance in the body. These include high and low pressure baroreceptors, intrarenal baroreceptors, renal autoregulation, tubuloglomerular feedback, aldosterone, and numerous other physical and hormonal factors. Sodium transport by the nephron involves active and passive processes which occur in several different nephron segments. Mechanisms of cotransport, Na(+)-H+ exchange, antiporters and ion-specific channels are all utilized by the nephron to maintain sodium balance. These regulatory factors and transport mechanisms for sodium in the kidney will he discussed in detail.

Biological Transport, Active↗

Chitosan-membrane interactions and their probable role in chitosan-mediated transfection.

Recent studies in our laboratory have shown that chitosan, a polycationic polymer of glucosamine, can facilitate the transfection of HeLa cells with a plasmid that codes for beta-galactosidase. Although chitosan can bind to DNA and other polyanions, the kinetics of complexation might differ depending on the polyanion tested. This evidence suggests that, in addition to ionic interactions, the carbohydrate backbone of chitosan might have an important role in the process of transfection. Beads prepared by the complexation of chitosan with polyphosphate were used to investigate the nature of cellular interactions with chitosan. HeLa cells bound to chitosan-polyphosphate beads could be readily displaced from the beads with methyl alpha-D-mannopyranoside but not with NaCl. Membrane proteins solubilized by CHAPS bound readily to chitosan-polyphosphate beads. A major fraction of the membrane proteins could be eluted from the beads with methyl alpha-D-mannopyranoside. These results suggest that non-ionic interactions between the carbohydrate backbone of chitosan and cell surface proteins might have an important role in the chitosan-mediated transfection of HeLa cells.

Biopolymers↗

A colorimetric assay method for 3beta-hydroxy-delta5-steroid dehydrogenase.

3beta-Hydroxy-Delta5-steroid dehydrogenase is an important enzyme of steroid hormone biosynthesis present in steroidogenic tissues like adrenal, testis, and ovary of vertebrates. The enzyme is assayed mainly by radiochemical substrates. Spectrophotometric assay is not adequately sensitive to detect the enzyme activity since it is often present in low levels. We have developed a simple colorimetric assay based on formazan formation due to the reduction of the tetrazolium salt. The reaction mixture containing the substrate, pregnenolone or dehydroepiandrosterone, NAD and iodonitrotetrazolium in 0.1 M Tris-HCl buffer (pH 7.8), and the enzyme extract is incubated for 1 h at 37 degrees C. Absorbance at 490 nm is read in a spectrophotometer. The enzyme activity was linear with time and protein concentration. The assay works well with adrenal tissue extract, whereas in the case of testis, Leydig cell preparation may be required. We have assayed the enzyme activity in the adrenal of rat, mouse, and gerbil. The method is two- to threefold more sensitive than the spectrophotometric assay.

Adrenal Glands↗

A study of structure of phenomenology of consciousness in meditative and non-meditative states.

Twelve senior Kundalini (Chakra) meditators were assessed during meditation session and non-meditation or control session using Phenomenology of Consciousness Inventory. The data has been analyzed using structural analysis to measure the altered state of consciousness and the identity state by comparing meditative state with non-meditative state. The structural analysis of pattern of consciousness during the meditative state revealed altered experience in perception (percentile rank PR = 90), meaning (PR = 82) and time sense (PR = 87), while positive affect dimension showed increased joy (PR = 73) and love (PR = 67). The imagery vividness (PR = 72), self-awareness (PR = 77), rationality (PR = 73) and arousal (PR = 69) were found to be structurally different from the ordinary state. With regards to identity state meditative experience was found to produce statistically significant changes in terms of intensity in meaning (P < 0.05), time sense (P < 0.05), joy (P < 0.05), love (P < 0.05) and state of awareness (P < 0.01). Our results indicate that long term practice of meditation appears to produce structural as well as intensity changes in phenomenological experiences of consciousness.

Adult↗

Intrinsic solubility estimation and pH-solubility behavior of cosalane (NSC 658586), an extremely hydrophobic diprotic acid.

PURPOSE: The selection of cosalane (NSC 658586) by the National Cancer Institute for further development as a potential drug candidate for the treatment of AIDS led to the exploration of the solubility behavior of this extremely hydrophobic drug, which has an intrinsic solubility (S0 approaching 1 ng/ml. This study describes attempts to reliably measure the intrinsic solubility of cosalane and examine its pH-solubility behavior. METHODS: S0 was estimated by 5 different strategies: (a) direct determination in an aqueous suspension: (b) facilitated dissolution; (c) estimation from the octanol/water partition coefficient and octanol solubility (d) application of an empirical equation based on melting point and partition coefficient; and (e) estimation from the hydrocarbon solubility and functional group contributions for transfer from hydrocarbon to water. RESULTS: S0 estimates using these five methods varied over a 5 x 107-fold range Method (a) yielded the highest values, two-orders of magnitude greater than those obtained by method (b) (facilitated dissolution. 1.4 +/- 0.5 ng/ml). Method (c) gave a value 20-fold higher while that from method (d) was in fair agreement with that from facilitated dissolution. Method (e) yielded a value several orders-of-magnitude lower than other methods. A molecular dynamics simulation suggests that folded conformations not accounted for by group contributions may reduce cosalane's effective hydrophobicity. Ionic equilibria calculations for this weak diprotic acid suggested a 100-fold increase in solubility per pH unit increase. The pH-solubility profile of cosalane at 25 degrees C agreed closely with theory. CONCLUSIONS: These studies highlight the difficulty in determining solubility of very poorly soluble compounds and the possible advantage of the facilitated dissolution method. The diprotic nature of cosalane enabled a solubility enhancement of > 107-fold by simple pH adjustment.

Anti-HIV Agents↗