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Biomedical subjects

S Basu

Publications and source records attributed to S Basu.

At least 127 records · Page 7Linked to original sources

Retinol palmitate counteracts oxidative injury during experimental septic shock.

INTRODUCTION: Retinols seem to be of clinical importance in ameliorating the clinical consequences of septic shock. These beneficial effects of retinols are suggested to be due to an antioxidant property. The present study was undertaken in order to confirm or rule out such an effect of retinol palmitate (RP) in experimental septic shock by measuring F2-isoprostanes and a major prostaglandin F2 alpha metabolite as indicators of oxidative injury and inflammatory response, respectively. MATERIALS AND METHODS: Fourteen anaesthetised pigs were randomly given an injection of RP (2.300 IU x kg-1) or the corresponding volume of vehicle. All pigs received a continuous infusion of E. coli endotoxin (10 micrograms x kg-1 x h-1). Blood samples were analysed for lipid peroxidation products (8-iso-PGF2 alpha), indicating free radical induced oxidative injury and 15-keto-dihydro-PGF2 alpha indicating cyclooxygenase-mediated inflammatory response). RESULTS: Significantly elevated levels of 8-iso-PGF2 alpha were seen at 3, 5 and 6 hours of endotoxaemia in the vehicle + endotoxin group as compared to RP + endotoxin group. Endotoxin induced cyclooxygenase-mediated inflammatory response was not affected by RP. CONCLUSIONS: This study is the first one to show that RP counteracts oxidative injury rather than inflammatory response in experimental septic shock. These results may be of importance for the understanding of some beneficial effects of RP during endotoxaemia (i.e. improved systemic haemodynamics and reduced serum levels of endotoxin). Our results may explain the therapeutic effects of nutrients rich in caroten/retinols used in some clinical studies.

Analysis of Variance↗

Impact of questionnaires and telephone screening on attendance for ambulatory surgery.

The purpose of this study was to determine whether patient questionnaires along with pre-operative telephone screening could help to reduce the number of cancellations or postponements of patients listed for day case endoscopy and local anaesthetic procedures and thereby provide cost effective and more efficient patient care management. A total of 566 questionnaires were sent out with a return figure of 477 (84.27%). Of those not returning the questionnaires, 56 (9.89%) were contacted by telephone giving an overall figure of 533 (94.16%) patients contacted. The cancellation rate for this group was only 2.25% compared to figures between 8-12% as noticed in the previous year. We conclude questionnaires along with telephone screening are a very effective tool in reducing cancellations and postponements of day case patients.

Ambulatory Surgical Procedures↗

Evidence for genetic linkage of Alzheimer's disease to chromosome 10q.

Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Abeta, the principal component of beta-amyloid and one of the neuropathological hallmarks of Alzheimer's disease (AD). We performed parametric and nonparametric linkage analyses of seven genetic markers on chromosome 10q, six of which map near the IDE gene, in 435 multiplex AD families. These analyses revealed significant evidence of linkage for adjacent markers (D10S1671, D10S583, D10S1710, and D10S566), which was most pronounced in late-onset families. Furthermore, we found evidence for allele-specific association between the putative disease locus and marker D10S583, which has recently been located within 195 kilobases of the IDE gene.

Age of Onset↗

Cutting edge: heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo.

Immunization of mice with the heat shock protein (HSP) gp96 but not control proteins leads to 5- to 7-fold enlargement of draining lymph nodes (LNs) resulting from accumulation of large numbers of mature CD11c(+) cells, but not T or B lymphocytes in them. The increase in size and cellularity is time-dependent; the draining LNs reach their peak size between 12 and 24 h after injection and regress to their normal size between 48 and 72 h after injection. The increment is elicited specifically in the draining LN but not in other LNs. This observation uncovers a novel aspect of HSP-APC interaction and adds to the mechanistic explanation for the unusually high immunogenicity of HSP-peptide complexes.

Animals↗

"Emergency" granulopoiesis in G-CSF-deficient mice in response to Candida albicans infection.

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein believed to play an important role in regulating granulopoiesis both at steady state and during an "emergency" situation. Generation of G-CSF and G-CSF receptor-deficient mice by gene targeting has demonstrated unequivocally the importance of G-CSF in the regulation of baseline granulopoiesis. This study attempted to define the physiologic role of G-CSF during an emergency situation by challenging a cohort of wild-type and G-CSF-deficient mice with Candida albicans. Interestingly, after infection, G-CSF-deficient mice developed an absolute neutrophilia that was observed both in blood and bone marrow. In addition, 3 days after Candida infection increased numbers of granulocyte-macrophage (GM) and macrophage (M) progenitors were observed in the bone marrow of G-CSF-deficient mice. Of the cytokines surveyed, interleukin (IL)-6 levels in serum were elevated; interestingly, levels of IL-6 were higher and more sustained in G-CSF-deficient mice infected with C albicans than similarly infected wild-type mice. Despite the higher levels of serum IL-6, this cytokine is dispensable for the observed neutrophilia because candida-infected IL-6-deficient mice, or mice simultaneously deficient in G-CSF and IL-6, developed neutrophilia. Similarly, mice lacking both G-CSF and GM-CSF developed absolute neutrophilia and had elevated numbers of GM and M progenitors in the bone marrow; thus, G-CSF and GM-CSF are dispensable for promoting the emergency response to candidal infection. (Blood. 2000;95:3725-3733)

Animals↗

Lipid peroxidation status, somatic mutations and micronuclei in peripheral lymphocytes: a case observation on a possible interrelationship.

A controlled dietary study was conducted in healthy female volunteers and reported elsewhere [1]. In a subset of samples four different biomarkers were analyzed: plasma malondialdehyde (MDA) levels and urinary 8-isoprostaglandin-F(2alpha) were measured as markers for lipid peroxidation. The frequency of hprt (hypoxanthine guanine phosphoribosyl transferase) mutants and micronuclei in peripheral blood lymphocytes were analyzed as indicators of genotoxic effects. One of the ten individuals showed extremely high background levels in all of the four endpoints measured. This case observation raises the possibility that life style factors and dietary habits affect the level of DNA reactive lipid peroxidation products, which in turn increase mutagenic and cytogenetic effects. A possible association between these biomarkers, particularly in relation to dietary fat intake and antioxidant status, should now be studied in a larger trial.

Adult↗

The Galactic Worm GW 123.4-1.5: A Mushroom-shaped H i Cloud.

The Dominion Radio Astrophysical Observatory's Synthesis Telescope provides the highest resolution data (1&arcmin; and 0.82 km s-1) to date of an H i worm candidate. Observed as part of the Canadian Galactic Plane Survey, mushroom-shaped GW 123.4-1.5 extends only a few hundred parsecs, contains approximately 105 M middle dot in circle of neutral hydrogen, and appears unrelated to a conventional shell or chimney structure. Our preliminary Zeus two-dimensional models use a single off-plane explosion with a modest ( approximately 1051 ergs) energy input. These generic simulations generate, interior to an expanding outer blast wave, a buoyant cloud whose structure resembles the morphology of the observed feature. Unlike typical model superbubbles, the stem can be narrow because its width is not governed by the pressure behind the blast wave or the disk scale height. Using this type of approach, it should be possible to more accurately model the thin stem and other details of GW 123.4-1.5 in the future.

Journal Article↗

Development of a novel biomarker of free radical damage in reperfusion injury after cardiac arrest.

In a porcine model of cardiopulmonary resuscitation (CPR), we investigated changes in the plasma levels of 8-iso-PGF(2alpha), a marker for oxidative injury, and 15-keto-dihydro-PGF(2alpha), an inflammatory response indicator during the post-resuscitation period after cardiac arrest. Twelve piglets were subjected to either 2 or 5 min (VF2 and VF5 group) of ventricular fibrillation (VF) followed by 5 min of closed-chest CPR. Six piglets without cardiac arrest were used as controls. In VF5 group, 8-iso-PGF(2alpha) in the jugular bulb plasma (draining the brain) increased four-fold. Jugular bulb 8-iso-PGF(2alpha) in the control group remained unchanged. The 15-keto-dihydro-PGF(2alpha) also increased four-fold in the VF5 group. Thus, 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) measurements in jugular bulb plasma may be used as biomarkers for quantification of free radical catalyzed oxidative brain injury and inflammatory response in reperfusion injury.

Animals↗

Conjugated linoleic acid induces lipid peroxidation in humans.

Conjugated linoleic acid (CLA) is shown to have chemoprotective properties in various experimental cancer models. CLA is easily oxidised and it has been suggested that an increased lipid oxidation may contribute to the antitumorigenic effects. This report investigates the urinary levels of 8-iso-PGF(2alpha), a major isoprostane and 15-keto-dihydro-PGF(2alpha), a major metabolite of PGF(2alpha), as indicators of non-enzymatic and enzymatic lipid peroxidation after dietary supplementation of CLA in healthy human subjects for 3 months. A significant increase of both 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) in urine was observed after 3 months of daily CLA intake (4.2 g/day) as compared to the control group (P<0.0001). Conjugated linoleic acid had no effect on the serum alpha-tocopherol levels. However, gamma-tocopherol levels in the serum increased significantly (P=0. 015) in the CLA-treated group. Thus, CLA may induce both non-enzymatic and enzymatic lipid peroxidation in vivo. Further studies of the mechanism behind, and the possible consequences of, the increased lipid peroxidation after CLA supplementation are urgently needed.

Adult↗

Partial rescue of the ocular retardation phenotype by genetic modifiers.

The or(J) allele of the murine ocular retardation mutation is caused by a premature stop codon in the homeodomain of the Chx10 gene. When expressed on an inbred 129/Sv strain, the or(J) phenotype is characterized by microphthalmia and a thin, poorly differentiated retina in which the peripheral portion is affected to a greater extent than the central portion. Such mutant retinae lack differentiated bipolar cells and the optic nerve typically fails to form, leading to blindness. Here, we show that progeny from an outcrossed backcross between 129/Sv-or(J) /or(J) and Mus musculus castaneus produce animals that are homozygous for the or(J) mutation and exhibit a much ameliorated eye phenotype. Although not of normal size, such modified or(J) eyes are significantly larger than those in 129/Sv-or(J) /or(J) mice, and contain a better organized retina which includes bipolar cells. Furthermore, optic nerves are frequently present, and the eyes show a degree of function as reflected by electroretinogram and pupillary response. As in 129/Sv-or(J) /or(J) mice, however, modified or(J) eyes show incomplete growth and a lack of cell differentiation in the periphery of the retina. The selective, and apparently nonmodifiable, effect of the ocular retardation phenotype on the periphery of the retina indicates that Chx10 plays an important role in the central-to-peripheral gradient of retinal development. These findings demonstrate that the ocular retardation phenotype can be greatly modified by the genetic background, and help to define a role for Chx10 in ocular development.

Animals↗

Dopamine, a neurotransmitter, influences the immune system.

Dopamine (DA) is a monoamine neurotransmitter of both central and peripheral nervous system. Its role in the neural-immune communication has been discussed in the present review. Results reveal that in vivo damage or stimulation of specific central dopaminergic system suppresses or enhances functional activities of the immune effector cells. The possible influences of other immunomodulators of the brain by altering brain DA may be the underlying mechanism. Direct effects of DA on the immune effector cells are also contradictory, it is suppressive in vitro, while in pharmacological doses, it is mostly stimulatory in vivo. The possible mechanisms have been discussed. Lastly, future areas of relevance on DA and immunity have been highlighted to advance our knowledge regarding DA as an immune regulator.

Animals↗

Prokinetic effect of black tea on gastrointestinal motility.

The gastrokinetic effects of hot water extract of black tea [Camellia sinensis, (L) O. Kuntze (Theaceae)] on gastrointestinal motility were studied both in vivo and in vitro. The extract significantly accelerated the gastrointestinal transit (GIT) in vivo in mice. These facilitatory effect was reduced after pretreatment with atropine, hemicholinium-3, morphine, indomethacin, McN-A-343 and L-arginine. In guinea pig ileum, the extract facilitated the peristaltic reflex in response to pressures in normal preparation. The black tea extract and L-NMMA (nitric oxide synthase inhibitor) significantly reduced the electrical field stimulated nonadrenergic, noncholinergic (NANC) relaxation of isolated rat fundal strips. The extract markedly enhanced the tonic ('hump') responses to transmural stimulation in longitudinal muscle of guinea pig ileum which was unaltered in the presence of atropine. These findings suggest a cholinergic involvement and a partial role of prostaglandin and nitric oxide in the mechanism of action of black tea extract on gastrointestinal motility. To determine the effective constituents in black tea responsible for this activity, the effect of black tea polyphenols on GIT were also studied. Thearubigin fraction (but not theaflavin) accelerated GIT significantly which suggests its involvement in the prokinetic effect of black tea.

Animals↗