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Biomedical subjects

S Kar

Publications and source records attributed to S Kar.

At least 73 records · Page 4Linked to original sources
PubMed1997

Distribution and levels of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor binding sites in the hippocampus of aged memory-unimpaired and -impaired rats.

The insulin-like growth factors (IGF-I and IGF-II) and insulin are localized within distinct brain regions and their respective functions are mediated by specific membrane receptors. High densities of binding sites for these growth factors are discretely and differentially distributed throughout the brain, with prominent levels localized to the hippocampal formation. IGFs and insulin, in addition to their growth promoting actions, are considered to play important roles in the development and maintenance of normal cell functions throughout life. We compared the anatomical distribution and levels of IGF and insulin receptors in young (five month) and aged (25 month) memory-impaired and memory-unimpaired male Long Evans rats as determined in the Morris water maze task in order to determine if alterations in IGF and insulin activity may be related to the emergence of cognitive deficits in the aged memory-impaired rat. In the hippocampus, [125I]IGF-I receptors are concentrated primarily in the dentate gyrus (DG) and the CA3 sub-field while high amounts of [125I]IGF-II binding sites are localized to the pyramidal cell layer, and the granular cell layer of the DG. [125I]insulin binding sites are mostly found in the molecular layer of the DG and the CA1 sub-field. No significant differences were found in [125I]IGF-I. [125I]IGF-II or [125I]insulin binding levels in any regions or laminae of the hippocampus of young vs aged rats. and deficits in cognitive performance did not relate to altered levels of these receptors in aged memory-impaired vs aged memory-unimpaired rats. Other regions. including various cortical areas, were also examined and failed to reveal any significant differences between the three groups studied. It thus appears that IGF-I, IGF-II and insulin receptor sites are not markedly altered during the normal ageing process in the Long Evans rat, in spite of significant learning deficits in a sub-group (memory-impaired) of aged animals. Hence. recently reported changes in IGF-I receptor messenger RNA levels in aged memory-impaired rats are apparently not reflected at the level of the translated protein.

Aging↗
PubMed1997

Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation.

Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [125I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [125I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [125I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [125I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [125I]insulin receptor binding was noted at all time points in the molecular layer of the dentate gyrus whereas binding in CA1-CA3 subfields and discrete layers of the Ammon's horn was found to be affected only after 12 h of treatment. These results, when analysed with reference to the observed histological changes and established neurotrophic/protective roles of insulin-like growth factors and insulin, suggest possible involvement of these growth factors in the cascade of neurotrophic events that is associated with the reorganization of the hippocampal formation observed following kainate-induced seizures.

Animals↗
PubMed1997

Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin-2 on the release of acetylcholine in rat hippocampal slices.

1. The biphasic nature of the potent modulatory action of interleukin-2 (IL-2) on hippocampal acetylcholine (ACh) release was investigated by use of brain slice superfusion. 2. Both the potentiating (10(-13) M) and inhibitory (10(-9) M) effects of IL-2 on hippocampal ACh release were stimulation-dependent and were blocked by a neutralizing IL-2 receptor antibody, suggesting the activation of typical IL-2 receptors in both cases. 3. Tetrodotoxin (TTX: 10 microM) failed to block the potentiation of ACh release induced by a very low concentration of IL-2 (10(-13) M) suggesting a direct effect on cholinergic nerve terminals. 4. In contrast, the inhibitory effect seen at a higher concentration (10(-9) M) was TTX-sensitive, and hence indicative of an indirect action. 5. To establish the nature of this intermediate mediator, blockers of nitric oxide synthesis, and of opioid and gamma-aminobutyric acid (GABA) receptors were used. Only GABAA and GABAB receptor antagonists altered the inhibitory action of IL-2, suggesting the participation of GABA as mediator. 6. Taken together, these results provide further evidence for the potent role of IL-2 in the modulation of cholinergic function in the rat hippocampus.

Acetylcholine↗
PubMed1997

Rearrangements in the genomes of Vibrio cholerae strains belonging to different serovars and biovars.

The intron-encoded enzyme I-CeuI provides an excellent tool for rapidly examining the organization of genomes of related species of bacteria. Vibrio cholerae strains belonging to serovars O1 and O139 have 9 I-ceuI sites in their genomes, and V. cholerae strains belonging to serovars non-O1 and non-O139 have 10 I-ceuI sites in their genomes. This information can be used as a criterion to differentiate O1 strains from non-O1 and non-O139 strains. To our knowledge, intraspecies variation in the number of rrn operons has not been reported in any other organism. Our data revealed extensive restriction fragment length polymorphism based on a comparison of the I-ceuI digestion profiles of strains belonging to different serovars and biovars. From the analysis of partial digestion products, I-CeuI macrorestriction maps of several classical, El Tor, and O139 strains were constructed. While the linkage maps are conserved within biovars, linkage maps vary substantially between biovars.

Cholera↗
PubMed1997

Unique organization of the CTX genetic element in Vibrio cholerae O139 strains which reemerged in Calcutta, India, in September 1996.

We studied the restriction fragment length polymorphism of the rRNA gene and CTX genetic element in Vibrio cholerae O139 Bengal, which resurged in Calcutta in September 1996 after a gap of 32 months. While the strains from this resurgence were indistinguishable from the earlier strains by ribotyping, the structure of the CTX genetic element present in the current O139 strains was found to be unconventional.

Cholera↗
PubMed1996

Integration of the DNA of a novel filamentous bacteriophage VSK from Vibrio cholerae 0139 into the host chromosomal DNA.

An unusual filamentous bacteriophage, VSK, containing single-stranded, circular DNA as its genome was isolated from Vibrio cholerae 0139 strains P07 and B04. Unlike other single-stranded DNA phages, VSK can integrate its genome into the chromosome of the host and enter into a lysogenic state. The double-stranded replicative form (RF) of the single-stranded phage DNA was isolated. A restriction map of the VSK RF DNA was constructed using HaeII, AvaII, ClaI and XbaI. By Southern blot analysis of the chromosomal DNA of the lysogen using labeled phage DNA as probe, the attachment site (attP) on the viral genome was also identified.

Bacteriophages↗
PubMed1996

Distribution and levels of insulin-like growth factor (IGF-I and IGF-II) and insulin receptor binding sites in the spinal cords of amyotrophic lateral sclerosis (ALS) patients.

The structurally related peptides, insulin and insulin-like growth factors (IGF-I and IGF-II), have neurotrophic properties and potentially could be of therapeutic value in human neurodegenerative disorders. In this study, we compared the anatomical distribution of [125I]IGF-I, [125I]IGF-II and [125I]insulin binding sites in thoracic spinal cords from patients who died of amyotrophic lateral sclerosis (ALS) and normal controls. For these three ligands, the greatest amounts of specific binding were located in the deeper layers of the dorsal horn > intermediate zone > lamina X > ventral horn > superficial layers of the dorsal horn > white matter of the spinal cord. Highly significant (P < 0.001) increases in the density of [125I]IGF-I and [125I]IGF-II binding were apparent in various laminae of the cord of ALS patients with increased binding being particularly evident in the ventral horn and the intermediate zone. Significant (P < 0.05) increases were also seen in lamina X and in the dorsal horn. In contrast, no significant differences in [125I]insulin binding were observed between ALS and control spinal cords. Taken together, these data reveal significant increases in both [125I]IGF-I and [125I]IGF-II binding levels in the spinal cords of ALS patients albeit to different extents. These findings may be of relevance for future therapeutic strategies aimed at slowing the progression of this chronic neurodegenerative disease, as recently suggested by the beneficial therapeutic effects of an IGF-I treatment in ALS patients.

Aged↗
PubMed1996

Measurement of phenols on a loop-supported liquid film by micellar electrokinetic chromatography and direct UV detection.

This paper describes a direct measurement of phenolic substances in the gas phase at levels relevant to occupational health by micellar electrokinetic chromatography (MEKC) using direct ultraviolet detection. A small circular loop (2 mm O.D.) is formed with 100 mm Pt-wire at the sampling end of a fused-silica capillary. The capillary tip of the sampling end is present at the center of the loop and in the same plane. A thin film of 0.50 mM NaOH is formed on the loop by immersion and withdrawal. The film is in fluid communication with the capillary and acts as an absorber for gaseous phenols. Gas sampling is performed by transferring the film-bearing loop into a chamber through which air is aspirated for a preset time at a preselected flow-rate (typically 1 min at 100 cm3/min). A part of the film content is then introduced into the capillary by gravity injection and then MEKC is performed. A total of twelve chloro- and nitrophenols were selected for this study. Under the above sampling conditions, limits of detection (LODs) for various phenols range from high-single-digit to low-double-digit ppbv levels. The effect of several critical parameters, such as the composition of the liquid film and the MEKC running electrolyte, sampling period and film evaporation on the collection efficiency, separation efficiency and calibration behaviour are described.

Adsorption↗
PubMed1996

A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia.

Tolerance to morphine analgesia is believed to result from a neuronal adaptation produced by continuous drug administration, although the precise mechanisms involved have yet to be established. Recently, we reported selective alterations in rat spinal calcitonin gene-related peptide (CGRP) markers in morphine-tolerant animals. In fact, increases in CGRP-like immunostaining and decrements in specific [125]hCGRP binding in the superficial laminae of the dorsal horn were correlated with the development of tolerance to the spinal antinociceptive action of morphine. Other spinally located peptides such as substance P, galanin, and neuropeptide Y were unaffected. Thus, the major goal of the present study was to investigate whether the development of tolerance to spinally infused morphine could be modulated by the blockade of dorsal horn CGRP receptors using the potent CGRP antagonist hCGRP(8-37). Indeed, cotreatments with hCGRP(8-37) prevented, in a dose-dependent manner, the development of tolerance to morphine-induced analgesia in both the rat tail-flick/tail-immersion and paw-pressure tests. Moreover, alterations in spinal CGRP markers seen in morphine-tolerant animals were not observed after a coadministration of morphine and hCGRP(8-37). These results demonstrate the existence of specific interaction between CGRP and the development of tolerance to the spinal antinociceptive effects of morphine. They also suggest that CGRP receptor antagonists could become useful adjuncts in the treatment of pain and tolerance to the antinociceptive effects of morphine.

Analgesics, Opioid↗
PubMed1996

Beta-amyloid-related peptides inhibit potassium-evoked acetylcholine release from rat hippocampal slices.

The 4 kDa beta-amyloid (A beta) protein, a major component of cerebral and cerebrovascular plaques in Alzheimer's disease (AD), is derived from the proteolytic cleavage of a larger, membrane-bound precursor, the A beta precursor protein (APP). Until recently, it was assumed that an aberrant AD-specific proteolysis generated A beta peptides, which subsequently could initiate and/or contribute to the pathological cascade leading to plaque formation and losses of selected neuronal populations, including basal forebrain cholinergic neurons that provide major inputs to the hippocampus and neocortex. However, the recent detection of soluble A beta fragments in the plasma and CSF of normal individuals, as well as in the conditioned media of cultured brain cells, suggests a role for A beta-related peptides in normal brain functions. Taking into consideration the reported toxic properties of A beta and the preferential vulnerability of basal forebrain cholinergic neurons in AD, we investigated the possible effects of A beta-related peptides on the release of endogenous acetylcholine (ACh) from rat brain slices. A beta 1-28, in a concentration-dependent manner (10(-12)-10(-8) M), potently inhibited K(+)-evoked ACh release from hippocampal slices. The inhibition of ACh release was fully reversible and was observed using other A beta-related peptides such as A beta 1-42, A beta 1-40, and A beta 25-35, but not with the scrambled, reverse, or all D-isomer A beta-peptide sequences, indicating that the effect of A beta on ACh release is mediated via a stereoselective mechanism. Tetrodotoxin (10 microM) failed to alter the effect of A beta 1-28 on ACh release, which suggests the lack of involvement of voltage-dependent Na+ channels. Except for the hippocampal formation, the inhibitory effect of A beta on K(+)-evoked ACh release also was observed in the frontal cortex but not in the striatum. Taken together, our results demonstrate that APP-derived A beta-related peptides can regulate the release of ACh potently by acting on cholinergic terminals. Additionally, the evidence that selected cholinergic neuronal populations are sensitive to A beta suggests a potential mechanistic link between the deposition of A beta and the preferential vulnerability of certain cholinergic projections in AD.

Acetylcholine↗
PubMed1996

Comitogenic effects of vasoactive intestinal polypeptide on rat hepatocytes.

The primary mitogens such as epidermal growth factor and transforming growth factor-alpha are known to stimulate DNA synthesis in primary cultures of adult rat hepatocytes. Vasoactive intestinal polypeptide (VIP) was found to amplify DNA synthesis induced by the primary mitogens and thus acted as a comitogen. The comitogenic effect of VIP was specific for the culture medium, suggesting that minor components in the medium were required for hepatocytes to fully respond to VIP. Glutamic acid is probably one of these minor components, although other components present in the nutrient-rich medium were also necessary for the full comitogenic effect. Other comitogens such as insulin, vasopressin, and angiotensin II interacted additively with low concentrations of VIP. The comitogenic effect of VIP was also found in hepatocytes cultured from regenerating rat liver after a partial hepatectomy. In the regenerating hepatocyte cultures, VIP can act as a mitogen even in the absence of the primary mitogen EGF. VIP mRNA was found in several organs including brain, intestine, and liver, and its expression was slightly induced in liver 24 h after a partial hepatectomy. These results suggest that VIP can act as a hepatic comitogen and may play a role in liver cell proliferation.

Animals↗
PubMed1996

Autoradiographical and immunohistochemical analysis of receptor localization in the central nervous system.

Quantitative receptor autoradiographic methods have been widely used over the past two decades. Some of the advantages and limitations of these techniques are reviewed here. Comparison with immunohistochemical and in situ hybridization methods is also highlighted, as well as the use of these approaches to study receptor gene over-expression in cell lines. Together, data obtained using these various methodologies can provide unique information on the potential physiological roles of a given receptor protein and/or binding sites in various tissues.

Animals↗
PubMed1996

Infarct size reduction with coronary venous retroinfusion of diltiazem in the acute occlusion/reperfusion porcine heart model.

Calcium channel blockers are commonly used for the treatment of ischemic heart disease, but their effects on myocardial infarct size (IS) after reperfusion are not well known. Enflurane-anesthetized open-chest pigs subjected to 60-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion were referred to one of the four experimental groups. Beginning 10 min before the onset of reperfusion, pigs in group A received diltiazem (7.5 micrograms/kg/min) retrogradely infused into the coronary vein for 30 min. In group B, the same amount of diltiazem was infused into the right atrium. A corresponding volume of saline was infused into the coronary vein in group C or into the right atrium in group D. IS expressed as a percentage of the myocardium at risk was significantly smaller (p < 0.01) in group A (33 +/- 14%; mean +/- SD) than in groups B (58 +/- 11%), C (58 +/- 11%), and D(63 +/- 10%). After reperfusion, functional recovery of the ischemic myocardium, determined by ultrasound crystals, was significantly more improved (p < 0.05) in group A as compared with other groups. The ischemic and nonischemic regional myocardial blood flow (RMBF), determined by radioactive microspheres, did not differ between four groups. Coronary venous retroinfusion of diltiazem had a myocardial protective effect in the porcine experimental model of acute coronary occlusion/reperfusion, whereas intravenous drug administration was not effective. The protective effect could not be attributed to washout of toxic metabolites from the ischemic area or to improved microcirculation. It was probably related to a pronounced accumulation of the calcium-channel blocker diltiazem in the ischemic myocardium achieved by the coronary venous route of delivery.

Animals↗
PubMed1996

Protective role of anion channel blocker in lipid peroxidation caused by H2O2 in microsomes of bovine pulmonary arterial smooth muscle tissue.

The role of hydroxyl radical (OH.) in H2O2-mediated stimulation of lipid peroxidation in microsomes of bovine pulmonary arterial smooth muscle tissue and the protective effects of DIDS, the anion channel blocker have been studied. Treatment of microsomes with H2O2 (1 mM) stimulate iron release, OH. production and lipid peroxidation. Pretreatment with DFO (an iron chelator) or DMTU (a hydroxyl radical scavenger) prevents OH. production and thereby reduces lipid peroxidation without any appreciable reduction of iron release. Simultaneous treatment of either DFO or DMTU with H2O2 significantly reduces lipid peroxidation and prevents OH. production without any significant reduction of iron release. However, addition of DFO or DMTU 2 min after treatment of the microsome with H2O2 does not produce any significant reduction of lipid peroxidation, OH production and iron release. Pretreatment of microsomes with DIDS markedly reduces the stimulation of lipid peroxidation without appreciably altering the increase in OH. production and iron release caused by H2O2.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗