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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 19 recordsLinked to original sources

Increase in weight induced by muraglitazar, a dual PPARalpha/gamma agonist, in db/db mice: adipogenesis/or oedema?

BACKGROUND AND PURPOSE: Muraglitazar, a dual PPARalpha/gamma agonist, caused a robust increase in body weight in db/db mice. The purpose of the study was to see if this increase in weight was due to oedema and/or adipogenesis. EXPERIMENTAL APPROACH: The affinity of muraglitazar at PPARalpha/gamma receptors was characterized using transactivation assays. Pre-adipocyte differentiation, expression of genes for adipogenesis (aP2), fatty acid oxidation (ACO) and sodium reabsorption (ENaCgamma and Na+, K+-ATPase); haemodilution parameters and serum electrolytes were measured to delineate the role of muraglitazar in causing weight gain vis a vis rosiglitazone. KEY RESULTS: Treatment with muraglitazar (10 mg kg(-1)) for 14 days significantly reduced plasma glucose and triglycerides. Reduction in plasma glucose was significantly greater than after similar treatment with rosiglitazone (10 mg kg(-1)). A marked increase in weight was also observed with muraglitazar that was significantly greater than with rosiglitazone. Muraglitazar increased aP2 mRNA and caused adipocyte differentiation in 3T3-L1 cells similar to rosiglitazone. It also caused a marked increase in ACO mRNA in the liver of the treated mice. Expression of mRNA for ENaCgamma and Na+, K+-ATPase in kidneys was up-regulated after either treatment. Increased serum electrolytes and decreased RBC count, haemoglobin and haematocrit were observed with both muraglitazar and rosiglitazone. CONCLUSIONS AND IMPLICATIONS: Although muraglitazar has a better glucose lowering profile, it also has a greater potential for weight gain than rosiglitazone. In conclusion, muraglitazar causes both robust adipogenesis and oedema in a 14-day treatment of db/db mice as observed in humans.

3T3-L1 Cells↗

Dialysis and nanotechnology: now, 10 years, or never?

Nanotechnology, defined as the science of material features between 10(-9) and 10(-7) of a meter, has received extensive attention in the popular press as proof-of-concept experiments in the laboratory are published. The inevitable delay between feature articles and clinical endpoints has led to unwarranted skepticism about the applicability of the technology to current medical therapy. The theoretic advantages of micro- and nanometer scale engineering to renal replacement include the manufacture of high-hydraulic permeability membranes with implanted sensing and control structures. Recent data in membrane design and testing is presented, with a review of the challenges remaining in implementation of this technology.

Extracellular Fluid↗

Dissociation between adipose tissue fluxes and lipogenic gene expression in ob/ob mice.

Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using (2)H(2)O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob, leptin-treated ob/ob, food-restricted ob/ob, and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 microg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux.

Adipogenesis↗

Caspase-3 cleaved spectrin colocalizes with neurofilament-immunoreactive neurons in Alzheimer's disease.

Corticocortical disconnection in Alzheimer's disease occurs by the progressive impairment and eventual loss of a small subset of pyramidal neurons in layers III and V of association areas of the neocortex. These neurons exhibit large somatic size, extensive dendritic arborization and high levels of nonphosphorylated neurofilaments of medium and high molecular weight that can be identified using a monoclonal SMI-32 antibody. It is thought that the accumulation of amyloid Abeta and neurofibrillary tangles may provoke metabolic disturbances that result in the loss of these SMI-32 immunoreactive neurons. The recent detection of increased levels of caspase-3 cleaved fodrin in frontal, temporal and parietal association areas in Alzheimer's disease brains suggests that programmed cell death may contribute to the destruction of SMI-32 positive neurons. In the present study, we utilized an antibody that selectively recognizes the 120 kDa breakdown product of alphaIIspectrin (fodrin) generated by caspase-3 to determine whether this protease is activated in vulnerable pyramidal neurons located in layers III and V of Alzheimer's disease brains. Neurons immunoreactive for caspase-3 cleaved alphaIIspectrin were located predominantly in layers III and V of the inferior frontal and superior temporal cortices of patients with Alzheimer's disease but not age-matched controls. Pyramidal neurons immunoreactive for caspase-3 cleaved alphaIIspectrin invariably displayed SMI-32 immunoreactivity suggesting that caspase-3 activation is a pathological event that may be responsible for the loss of a subset of pyramidal neurons that comprise corticocortical projections.

Aged↗

Arsenic contamination in the Kanker district of central-east India: geology and health effects.

This paper identifies newer areas of arsenic contamination in the District Kanker, which adjoins the District Rajnandgaon where high contamination has been reported earlier. A correlation with the mobile phase episodes of arsenic contamination has been identified, which further hinges on the complex geology of the area. Arsenic concentrations in both surface and groundwater, aquatic organisms (snail and water weeds) soil and vegetation of Kanker district and its adjoining area have been reported here. The region has been found to contain an elevated level of arsenic. All segments of the ecoysystem are contaminated with arsenic at varying degrees. The levels of arsenic vary constantly depending on the season and location. An analysis of groundwater from 89 locations in the Kanker district has shown high values of arsenic, iron and manganese (mean: 144, 914 and 371 microg L(-1), respectively). The surface water of the region shows elevated levels of arsenic, which is influenced by the geological mineralised zonation. The most prevalent species in the groundwater is As(III), whereas the surface water of the rivers shows a significant contamination with the As(V) species. The analysis shows a bio-concentration of the toxic metals arsenic, nickel, copper and chromium. Higher arsenic concentrations (groundwater concentrations greater than 50 microg L(-1)) are associated with sedimentary deposits derived from volcanic rocks, hence mineral leaching appears to be the source of arsenic contamination. Higher levels of arsenic and manganese in the Kanker district have been found to cause impacts on the flora and fauna. A case study of episodic arsenical diarrhoea is presented.

Adolescent↗

Liquid chromatography on porous graphitic carbon with atmospheric pressure photoionization mass spectrometry and tandem mass spectrometry for the analysis of glycosphingolipids.

The study of several structural variations (the length, the degree of unsaturation and hydroxylation of the alkyl chains, the number and nature of osidic residues) helped understand the behaviour of neutral glycosphingolipids (GSLs) on porous graphitic carbon stationary phase (PGC). Atmospheric pressure photoionization mass spectrometry (APPI) and tandem mass spectrometry were used to perform the detection and the identification of molecular species in positive mode where [M+H](+) and [M-H(2)O+H](+) ions provided structural information on the fatty acid and the sphingoid base. The retention of GSLs increased with the hydrocarboneous volume of their alkyl chains and with the number of osidic residues in agreement with hydrophobic properties and polar retention effect of graphite, respectively. The presence of polar groups, such as OH-group or double bond within alkyl chains, decreased their retention. The coupling of chromatography on PGC with APPI tandem mass spectrometry detection appeared a powerful technique to discriminate isobaric molecules. Isobaric solutes differing by the position of two double bonds or by the repartition of hydrocarboneous skeleton were discriminated according to their chromatographic comportment or their mass spectrum, respectively. Among isobaric molecules, only few structures differing by the nature of osidic residue were not discriminated (i.e. glucosylceramide and galactosylceramide with similar ceramide skeleton were co-eluted and no difference in mass spectra was observed).

Atmospheric Pressure↗

Tail hair as an indicator of environmental exposure of cows to lead and cadmium in different industrial areas.

This study examines the use of tail hair from cows as a possible biomarker of environmental exposure to lead and cadmium around different industrial areas. Respective blood and tail hair samples were collected from a total of 317 apparently healthy cows above 3 years of age. This includes 287 cows reared in industrial and urban areas and 30 cows from areas free from polluting sources. Significantly (P<0.05) higher lead and cadmium residues were recorded in hair from cows reared around lead-zinc smelter and closed lead cum operational zinc smelter. However, cows from those areas had significantly (P<0.05) higher blood lead but not cadmium concentration as compared to respective control value. Although mean blood lead concentration in cows around aluminum processing plant and urban cum small industrial areas and that of cadmium around steel processing plant were significantly (P<0.05) higher than respective control, the mean hair lead and cadmium content remained statistically (P>0.05) comparable to that of respective control values. The blood lead was significantly correlated with hair lead (r = 0.672, P<0.01) and cadmium (r = 0.309, P<0.05). There was a significant correlation between lead and cadmium concentration (r = 0.610, P<0.01) in hair and a nonsignificant correlation between blood and hair cadmium suggesting that cadmium accumulation in hair was influenced by blood and hair lead concentrations in cows environmentally exposed to lead.

Animals↗

[Evolution of cardiac risk factors management among patients aged 65 years and older with coronary artery disease].

The aim of this retrospective study was to compare the appropriateness of cardiac risk factors (CV-RF) management in a Swiss cardiac rehabilitation center. The comparison of the control of CV-RF among 342 patients with coronary artery disease (CHD) aged > or =65 years was improved. The CV-RF management has globally improved during the two periods of observation (1994-95 and 1999-2000). Nevertheless, according to the recommendations published between 1994 and 1999, an underuse of the cardioprotective agents was still observed. Using a standardized protocol for the management of CHD which allows the benchmarking among the network of cardiac rehabilitation centers network could increase the quality of care for such high risk patients.

Aged↗

Euler buckling-induced folding and rotation of red blood cells in an optical trap.

We investigate the physics of an optically driven micromotor of biological origin. When a single, live red blood cell (RBC) is placed in an optical trap, the normal biconcave disc shape of the cell is observed to fold into a rod-like shape. If the trapping laser beam is circularly polarized, the folded RBC rotates. A model based on geometric considerations, using the concept of buckling instabilities, captures the folding phenomenon; the rotation of the cell is rationalized using the Poincaré sphere. Our model predicts that (i) at a critical power of the trapping laser beam the RBC shape undergoes large fluctuations, and (ii) the torque that is generated is proportional to the power of the laser beam. These predictions are verified experimentally. We suggest a possible mechanism for the emergence of birefringent properties in the RBC in the folded state.

Animals↗

Solar disinfection of water for diarrhoeal prevention in southern India.

AIMS: To evaluate the efficacy and acceptability of solar irradiation in the prevention of diarrhoeal morbidity in children under 5 years of age, in an urban slum in Vellore, Tamil Nadu. METHODS: A total of 100 children were assigned to receive drinking water that had been subjected to solar disinfection in polyethylene terephthalate bottles. One hundred age and sex matched controls were also selected. Both groups were followed by weekly home visits for a period of six months for any diarrhoeal morbidity. At the end of the follow up period, the acceptability of the intervention was assessed by interviews, questionnaires, and focus group discussions. RESULTS: There was significant reduction in the incidence, duration, and severity of diarrhoea in children receiving solar disinfected water, despite 86% of the children drinking water other than that treated by the intervention. The incidence of diarrhoea in the intervention group was 1.7 per child-year, and among controls 2.7 per child-year, with an incidence rate ratio of 0.64 (95% CI -0.48 to 0.86). The risk of diarrhoea was reduced by 40% by using solar disinfection. In qualitative evaluation of acceptability, most women felt that solar disinfection was a feasible and sustainable method of disinfecting water. CONCLUSIONS: Solar disinfection of water is an inexpensive, effective, and acceptable method of increasing water safety in a resource limited environment, and can significantly decrease diarrhoeal morbidity in children.

Child, Preschool↗

A comparative study on the efficacy of rofecoxib in monoarticular arthritis induced by latex of Calotropis procera and Freund's complete adjuvant.

The role of prostaglandins in Calotropis procera latex induced inflammation and hyperalgesia has been well established. The acute inflammation induced by the dried latex (DL) of this plant could be effectively ameliorated by standard anti-inflammatory drugs. In present study we have evaluated the efficacy of rofecoxib, a COX-2 inhibitor in monoarthritis induced by intra-articular injection of DL and compared it with that against Freund's Complete Adjuvant (FCA). DL and FCA were injected into the right ankle joint of the rat and the joint diameter was measured by a micrometer screw gauge on day 0, 4, 8, 12, 20 and 28. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test and compression test. The effect of rofecoxib was evaluated on these parameters in both the models. Both DL and FCA produced peak inflammation on day 4 that was associated with decreased pain threshold and functional impairment. Although rofecoxib was more effective in improving motility in the DL model, its effect on joint inflammation, hyperalgesia and stair climbing ability was comparable in both the models. Thus, our study indicates that DL induced monoarthritis could be used as a model for the screening and evaluation of anti-inflammatory and anti-arthritic drugs.

Administration, Oral↗

[Imaging mass spectrometry: a new tool for the analysis of skin biopsy. Application in Fabry's disease].

The advent of innovative techniques in mass spectrometry, especially in the area of imaging, prompted us to evaluate two promising techniques: secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. For this purpose, sections of cutaneous biopsies from patients affected by Fabry's disease and control patients were analyzed. In the course of this disease, two physiological glycosphingolipids [globotriasylceramide (Gb3) and the galabiosylceramide (Ga2)] accumulate in certain tissues owing to a catabolism failure. The ability of these techniques to localize sites of accumulation in body tissues and their capacity to identify the accumulated lipid structures by mass spectra were evaluated. Results demonstrated that these two techniques provide complementary information:-secondary ion mass spectrometry enabled precise localization of areas of accumulation with lateral resolution in the micrometer range;-the signal obtained with matrix-assisted laser desorption/ionization mass spectrometry was high enough to identify these structures according to their molecular weight.

Diagnostic Imaging↗

[Dosage and kinetics of MMC release of a collagen implant used as a delivery device in glaucoma surgery in the rabbit eye].

PURPOSE: To determine the absorption and the release of mitomycin-C from a collagen implant and tissue impregnation in the anterior structures of the rabbit eye. METHODS: Determining the quantity of mitomycin-C that a collagen implant can absorb with the difference between dry and soaked weight. Mitomycin-C release was measured in vitro using spectrophotometry. The measurement was repeated using a bioassay. Ocular tissue impregnation was determined in 12 eyes of six rabbits. Sclera, implant, aqueous, and ciliary body specimens were collected for concentration measurement using HPLC from 1 to 6 h after surgery. RESULTS: The mean mitomycin-C quantity absorbed in the implant was 3.22+/-0.2 microg. In vitro release was 0.13 mg/ml after 10 min and 0.05 microg/ml at 6 h. The bioassay showed almost no antifibrotic activity in sclera. In vivo release of mitomycin-C was high from the first to the sixth hour. CONCLUSION: After filtering surgery, mitomycin-C in the collagen implant is clearly released and ocular tissues are effectively impregnated.

Animals↗

[Deep nonpenetrating sclerectomy: technical aspects].

Classical trabeculectomy is affected by numerous and serious drawbacks that have led to the development of nonpenetrating surgery. In this new filtering technique, the aqueous outflow through the juxtacanalicular trabeculum and Schlemm's canal is selectively increased without penetrating the anterior chamber. This is best performed by means of a careful and precise dissection of the outflow resistance pathway and by removing its most resistant portion. This requires both mastery of the microdissection technique and high-precision surgical tools. Finally, sound knowledge of the morphological features of such delicate structures is of paramount importance to avoid intra- and postoperative complications.

Glaucoma↗

[How does nonpenetrating surgery work?].

The aqueous leaves the anterior segment via two different pathways, the classical and the uveoscleral routes. The main resistance to aqueous egress lies at the level of the juxtacanalicular trabeculum and the inner wall of Schlemm's canal. Impaired function of either one of these structures leads to a decrease in the outflow facility which eventually results in a significant increase in intraocular pressure. Success of non-penetrating surgery lies in the physical removal of these resisting elements without compromising of the structural integrity of the eye, thus preventing a sudden drop in the intraocular pressure. The selective filtration through the trabeculodescemetic membrane, the evacuation of the aqueous in the intrascleral space, the subconjunctival bleb and the subchoroidal space, and the final drainage into collector channels and drain veins are the key elements for a successful deep sclerectomy.

Humans↗

[Adjuvants to nonpenetrating surgery: drains and implants].

The nonpenetrating filtering procedure requires a functioning intrascleral space. This space is created after a careful dissection and resection of the deep scleral flap. In order to prevent a collapse of the remaining superficial flap that forms the roof of the intrascleral cavity, a space maintainer is usually inserted at this stage of surgery. Two different types of drainage devices are used: absorbable and nonabsorbable implants. The first type is currently made of porcine collagen material that is slowly absorbed over time, whereas the second is usually made of nondegradable materials that permanently remain in the scleral bed. No significant differences in the surgical technique can be found between the two types of implant. The long-term results are fairly similar for both of them, the absorbable implant being slightly more advantageous.

Dissection↗