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Biomedical subjects

K Mukherjee

Publications and source records attributed to K Mukherjee.

At least 19 recordsLinked to original sources
PubMed2001

Ventromedial hypothalamic mediation of sucrose feeding induced pain modulation.

Electrophysiological and behavioural studies suggest a modulatory role of ventromedial nucleus of the hypothalamus (VMH) in nociceptive behaviour. Lesion of the VMH produces hyperalgesia and a greater preference for sucrose solution. Hyperalgesia is also produced by sucrose feeding. To explore specifically the contribution of glucoreceptor neurons of the VMH in the mediation of sucrose-fed hyperalgesia, 2-deoxy-D-glucose (2-DG, antimetabolite of glucose) was slowly albeit continuously infused (1 microl/h for 7 days by microinfusion pumps) into the VMH of adult male rats. Simultaneously, the rats underwent tests for their nociceptive responses in control and sucrose-fed states. The tests for nociception, namely, tail flick latency (TFL), thresholds of tail flick (TF), vocalization during stimulus (SV), vocalization after discharge (VA) were recorded at 0500 h. The tests were repeated after 6, 12, and 48 h in 1 M saline (control group) and 2-DG (experimental group) microinfused rats. Rats were presented with sucrose (20%) solution for 48 h at 0500 h ad libitum in addition to food pellets and tap water. Infusion of 2-DG per se in the VMH led to hypoalgesia (in threshold of TF, SV, VA) while feeding sucrose for 6-12 h per se led to hyperalgesia (in TFL, threshold of SV and VA). Sucrose feeding to 2-DG rats, however, attenuated the hypoalgesia of 2-DG as well as the hyperalgesia of sucrose feeding. The results suggest that the VMH glucoreceptor neurons probably modulate sucrose mediated phasic pain responses.

Animals↗
PubMed2001

Effect of VMH lesion on sucrose-fed analgesia in formalin pain.

The ingestion of sucrose (ad libitum) produces an immediate analgesic response to phasic noxious stimuli. The underlying mechanism for the analgesic effect of sucrose is attributed to its palatability, which mediates analgesia probably by the release of beta-endorphin in the hypothalamus. The present study was designed to explore the role of ventromedial hypothalamus in the mediation of sucrose-fed analgesia. Adult male albino rats each received (20%) sucrose solution orally through a separate bottle until they had ingested 4-5 ml. Their behavioral responses to tonic noxious stimulus in a formalin test were studied in pre- and postsucrose-fed rats of control and in the VMH lesion groups. The average pain rating of a 60-min session significantly (p < 0.01) decreased after sucrose feeding in control rats, from 1.94 +/- 0.13 to 1.45 +/- 0.14, but sucrose feeding by the VMH lesion rats did not alter their tonic nociceptive response from a 1.70 +/- 0.07 presucrose-fed state to a 1.71 +/- 0.08 postsucrose-fed state. VMH lesion per se did not alter the nociceptive response in comparison with controls. The results suggest that sucrose feeding produces analgesia to tonic noxious stimulus, which is abolished by lesion of the VMH, thereby indicating a significant role of VMH in sucrose-fed analgesia.

Analgesia↗
PubMed2000

Live Salmonella modulate expression of Rab proteins to persist in a specialized compartment and escape transport to lysosomes.

We investigated the intracellular route of Salmonella in macrophages to determine a plausible mechanism for their survival in phagocytes. Western blot analysis of isolated phagosomes using specific antibodies revealed that by 5 min after internalization dead Salmonella-containing phagosomes acquire transferrin receptors (a marker for early endosomes), whereas by 30 min the dead bacteria are found in vesicles carrying the late endosomal markers cation-dependent mannose 6-phosphate receptors, Rab7 and Rab9. In contrast, live Salmonella-containing phagosomes (LSP) retain a significant amount of Rab5 and transferrin receptor until 30 min, selectively deplete Rab7 and Rab9, and never acquire mannose 6-phosphate receptors even 90 min after internalization. Retention of Rab5 and Rab18 and selective depletion of Rab7 and Rab9 presumably enable the LSP to avoid transport to lysosomes through late endosomes. The presence of immature cathepsin D (48 kDa) and selective depletion of the vacuolar ATPase in LSP presumably contributes to the less acidic pH of LSP. In contrast, proteolytically processed cathepsin D (M(r) 17,000) was detected by 30 min on the dead Salmonella-containing phagosomes. Morphological analysis also revealed that after uptake by macrophages, the dead Salmonella are transported to lysosomes, whereas the live bacteria persist in compartments that avoid fusion with lysosomes, indicating that live Salmonella bypass the normal endocytic route targeted to lysosomes and mature in a specialized compartment.

Adenosine Triphosphatases↗
PubMed2000

Live Salmonella recruits N-ethylmaleimide-sensitive fusion protein on phagosomal membrane and promotes fusion with early endosome.

To understand intracellular trafficking modulations by live Salmonella, we investigated the characteristics of in vitro fusion between endosomes and phagosomes containing live (LSP) or dead Salmonella (DSP). We observed that fusion of both DSP and LSP were time, temperature and cytosol dependent. GTPgammaS and treatment of the phagosomes with Rab-GDI inhibited fusion, indicating involvement of Rab-GTPases. LSP were rich in rab5, alpha-SNAP, and NSF, while DSP mainly contained rab7. Fusion of endosomes with DSP was inhibited by ATP depletion, N-ethylmaleimide (NEM) treatment, and in NEM-sensitive factor (NSF)-depleted cytosol. In contrast, fusion of endosomes with LSP was not inhibited by ATP depletion or NEM treatment, and occurred in NSF-depleted cytosol. However, ATPgammaS inhibited both fusion events. Fusion of NEM-treated LSP with endosomes was abrogated in NSF- depleted cytosol and was restored by adding purified NSF, whereas no fusion occurred with NEM-treated DSP, indicating that NSF recruitment is dependent on continuous signals from live Salmonella. Binding of NSF with LSP required prior presence of rab5 on the phagosome. We have also shown that rab5 specifically binds with Sop E, a protein from Salmonella. Our results indicate that live Salmonella help binding of rab5 on the phagosomes, possibly activate the SNARE which leads to further recruitment of alpha-SNAP for subsequent binding with NSF to promote fusion of the LSP with early endosomes and inhibition of their transport to lysosomes.

Adenosine Triphosphate↗
PubMed2000

Evaluation of antipyretic potential of Nelumbo nucifera stalk extract.

The ethanol extract of stalks of Nelumbo nucifera (NNSE) was evaluated for its antipyretic potential on normal body temperature and yeast induced pyrexia in rats. NNSE showed significant activity in both the models at oral doses of 200 and 400 mg/kg. NNSE at a dose of 200 mg/kg was found to produce significant lowering of normal body temperature up to 3 h and at 400 mg/kg it caused significant lowering of body temperature up to 6 h after its administration. In the model of yeast provoked elevation of body temperature NNSE showed dose-dependent lowering of body temperature up to 4 h at both the doses and the results were comparable to that of paracetamol, a standard antipyretic agent.

Analgesics, Non-Narcotic↗
PubMed2000

Evaluation of antidiarrhoeal profile of Jussiaea suffruticosa linn. extract in rats.

The antidiarrhoeal potential of a methanol extract of the aerial parts of Jussiaea suffruticosa Linn. (MEJS) was studied with several experimental models of diarrhoea in rats. MEJS treated rats showed significant inhibitory activity against castor oil induced diarrhoea and PGE(2) induced enteropooling. It also showed a significant reduction in gastrointestinal motility following a charcoal meal in rats. The extract exhibited significant antidiarrhoeal potential at doses of 100,200 and 300 mg/kg in all the animal models and thus established the efficacy of MEJS as a potent antidiarrhoeal agent.

Animals↗
PubMed2000

Diabetes-induced myocardial structural changes: role of endothelin-1 and its receptors.

Several metabolic abnormalities may be triggered secondary to hyperglycemia in diabetes. Some of these abnormalities may alter expression of vasoactive factors in the target organs of diabetic complications. We investigated alterations of endothelin-1 (ET-1) and its receptors, ET(A) and ET(B), and associated structural changes in the myocardium of streptozotocin-induced diabetic rats after 6 months of hyperglycemia. We further assessed the preventive effects of an ET-receptor antagonist bosentan on these changes. Compared to the non-diabetic, age- and sex-matched control animals, diabetic rats showed hyperglycemia, glucosuria, reduced body weight gain and elevated glycated Hb levels. Measurement of ET-1, ET(A) and ET(B) mRNAs by semiquantitative RT-PCR showed significantly increased mRNA levels in the hearts of diabetic rats. Treatment with bosentan failed to reduce ET-1 or ET(B) mRNA expression in diabetes, however ET(A) mRNA expression was reduced. Immunocytochemically, ET-1 was detected in the cardiomyocytes, endothelium and smooth muscle cells of the larger blood vessels and was increased in diabetes. Autoradiographic localization of ET-1 receptors, using (125)I-ET-1, showed increased binding in the endothelium and myocardium of diabetic animals. Histologically, focal fibrous scarring with apoptotic cardiomyocytes, consistent with changes secondary to microvascular occlusion, was only present in the diabetic rats. In keeping with focal fibrosis, myocardium from diabetic rats further showed significantly increased mRNA expression of two extracellular matrix protein transcripts, fibronectin and collagen alpha 1(IV) which were completely prevented by treatment with bosentan. These data suggest that hyperglycemia-induced upregulation of the ET-system in the heart may be important in the pathogenesis of cardiac involvement in diabetes.

Animals↗
PubMed2000

Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism.

This paper explores the role of endothelins (ETs) in diabetes-induced testicular damage by investigating, in a temporal manner, testes from streptozotocin (STZ)-induced diabetic rats. Testicular and epididymal weights and testicular morphology were assessed. Cell death was evaluated by light microscopy using conventional staining and morphology, and by apoptotic cell staining using the Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling (TUNEL) technique. Expression of endothelin-1 (ET-1) mRNA was evaluated by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Furthermore, effects of a mixed ETA and ETB receptor antagonist, bosentan, were studied. Testicular weights did not show any change at 1 month of follow-up, but were decreased after 6 months of diabetes. However, epididymal weights were significantly decreased at the end of both time periods in the diabetic rats. Morphological evaluations of the testes from diabetic rats showed a reduction in seminiferous tubular diameter, an increase in the number of empty testicular tubules and an increase in vascular density. Furthermore, degenerated germ cells and TUNEL-positive cells were significantly higher in diabetic rats than in control animals. The changes in diabetic animals were associated with increased ET-1 mRNA expression and were prevented by bosentan treatment. Administration of bosentan prevented decreased testicular weights, reduced seminiferous tubule diameters, increased vascular densities and incidences of degenerated and apoptotic germ cells and empty tubules in diabetic rats at the long-term follow-up. These results demonstrated that an ET-1 mediated pathway might be involved in testicular injury and germ-cell apoptosis in diabetes.

Animals↗
PubMed2000

Endothelins, their receptors, and retinal vascular dysfunction in galactose-fed rats.

PURPOSE: Endothelins are potent vasoactive factors that have been implicated in the pathogenesis of several vascular disorders. This study was conducted to determine the role that endothelins play in the development of retinal microangiopathy under hyperhexosemic conditions induced by galactose feeding. METHODS: Retinal blood flow was determined using Doppler sonography in galactose fed rats with or without an endothelin receptor antagonist (Bosentan) treatment and were compared to control rats after 1 and 6 months of follow-up. Levels of endothelin-1, endothelin-3, (ET-1, ET3) and receptors endothelin A, endothelin B, (ET(A), ET(B)) mRNA expression were determined by semiquantitative RT-PCR. Immunohistochemical distribution of ET-1 and ET-3, ligand binding, and autoradiography to determine ET receptor distribution were carried out. RESULTS: Retinal vasoconstriction measured by an increase in resistivity index (RI) was present in 1 month galactose feeding compared to controls, which was prevented by Bosentan treatment. After 6 months of follow up all animal groups exhibited higher RI compared to their 1 month counterpart, although they were not different from each other. Compared to the controls, after 1 month levels of mRNA for ET-1, ET-3, and ET(A) were increased in galactose-fed rats, whereas ET(B) mRNA production remained similar to controls. After 6 months, all four genes exhibited increased levels compared to the controls, and no effect of Bosentan treatment on gene expression was evident. Increased immunoreactivity of ET-1 and ET-3 was determined, as well as increased ET receptor concentration was further present in the retina of galactose-fed animals. CONCLUSION: The data suggests that endothelin production is increased under hyperhexosemic conditions and that the endothelins play an important role in regulating the hemodynamics of retinal blood flow.

Animals↗
PubMed2000

Effect of VMH lesion on sucrose-Fed nociceptive responses.

An initial analgesia followed by hyperalgesia to phasic noxious stimuli occurs after ingestion of sucrose ad libitum. However, the mechanism underlying hyperalgesia is not known. The present study was designed to explore the role of VMH in the mediation of the hyperalgesic effect of sucrose ingestion. Adult male albino rats received sucrose solution (20% p.o.) in addition to laboratory food pellets and tap water ad libitum. Their behavioural responses to various phasic and tonic noxious stimuli were recorded after 6, 12 and 48 h during pre and post-sucrose fed states in both the control and VMH lesion groups of rats. Sucrose feeding to control rats significantly reduced the tail flick latency (TFL) and threshold of vocalization during stimulus (SV) and after discharge (VA) indicating hyperalgesia, while the threshold of tail flick remained unaffected. The average pain rating during the formalin test (tonic pain) decreased significantly indicating analgesia. VMH lesion decreased the latency (mean +/- SD) for tail flick (11.26 +/- 4.65 from 15.61 +/- 5.12 s), threshold (median) for tail flick (0.04 from 0.08 mA), vocalization during stimulus (0.05 from 0.1 mA) and vocalization after discharge (0.15 from 0.2 mA), while the tonic pain rating increased, thereby suggesting a hyperalgesic state. However, sucrose feeding to lesioned rats neither potentiated nor attenuated their hyperalgesia. The results suggest that sucrose feeding for 6-48 h ad libitum produces hyperalgesia to phasic noxious and analgesia to tonic noxious stimuli, while VMH lesion produces hyperalgesia to both phasic and tonic noxious stimuli. Secondly, sucrose ingestion by VMH lesion rats does not affect their responses to pain, suggesting the possible role of VMH in the mediation of sucrose-fed nociceptive responses.

Animals↗
PubMed1999

Surface Enhanced Raman Spectroscopic Study of Isomeric Methylthiophenes in Silver Colloid.

Surface Enhanced Raman Spectra (SERS) of 2-methylthiophene (2-MT) and 3-methylthiophene (3-MT) in silver colloid are compared with their normal Raman spectra in the bulk and in acetonitrile solution. Experimental results indicate that both the methylthiophene molecules are adsorbed on a metal surface through the sulfur atom. Assuming the image dipole theory to be valid, the observed surface enhancement factor of the C-H stretching mode in 2-MT indicates that the C-H bond of this isomer makes an angle of 51 degrees with the surface normal. The experimental results further suggest that the 3-MT molecule is adsorbed with its ring plane almost vertical to the metal surface; the 2-MT molecule, on the other hand, is tilted more than 45 degrees to the surface normal. The concentration dependence of the relative enhancement factor indicates that a monomolecular layer is formed on the metal surface at a specific concentration of the methylthiophenes in silver sol. No oligomerization of the two methylthiophenes on the silver surface is observed. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Diabetes-induced vascular dysfunction in the retina: role of endothelins.

AIMS/HYPOTHESIS: Vasoactive factors like endothelins, by virtue of the microvascular regulation as well as by other effects, possibly play important parts in the pathogenesis of diabetic retinal microangiopathy. We investigated retinal vascular dysfunction in streptozotocin-induced diabetes and its relation with endothelins in short- and long-term diabetes. METHODS: Diabetic rats with or without an endothelin receptor antagonist (bosentan) treatment were investigated after 1 month and 6 months of follow-up. Retinal blood flow was measured and compared with age- and sex-matched non-diabetic control animals. Retinal tissues were analysed for endothelin-1, endothelin-3, endothelin A and endothelin B mRNA. Distribution of endothelin-1 and endothelin-3 was investigated by immunocytochemistry and that for endothelin receptors by ligand binding and autoradiography. RESULTS: Diabetic animals showed hyperglycaemia, glycosuria, elevated glycated haemoglobin values and reduced body weight gain. Retinal blood flow showed an increased resistivity index, an indicator of vasoconstriction, after 1 month of diabetes which was prevented by treatment with bosentan. This functional change in diabetes was eliminated after 6 months of follow-up. The retina from the diabetic animals showed increased mRNA expression for endothelin-1, endothelin-3 and endothelin A after one month. In addition, endothelin B mRNA expression was increased after 6 months. Furthermore, endothelin-1 and endothelin-3 immunoreactivity and endothelin receptor concentrations were increased in the retina of diabetic rats. CONCLUSION/INTERPRETATION: The results from this study indicate that the endothelin system is of importance in mediating retinal changes in diabetes although mechanisms of the endothelin system alteration as well as their effects might vary depending on the duration of diabetes. [Diabetologia (1999) 42: 1228-1234]

Animals↗
PubMed1999

Evaluation of hepatoprotective activity of Cassia fistula leaf extract.

Hepatoprotective activity of the n-heptane extract of Cassia fistula leaves was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). The extract has been shown to possess significant protective effect by lowering the serum levels of transminases (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). The extract of C. fistula at a dose of 400 mg/kg showed significant hepatoprotective activity which was comparable to that of a standard hepatoprotective agent.

Alanine Transaminase↗
PubMed1999

GroEL is involved in activation of Escherichia coli RNA polymerase devoid of the omega subunit in vivo.

Highly purified Escherichia coli RNA polymerase contains a small subunit termed omega that has a molecular mass of 10 105 Da and is comprised of 91 amino acids. E. coli strains lacking omega (omega-less) are viable, but exhibit a slow-growth phenotype. Renaturation of RNA polymerase isolated from an omega-less mutant, in the presence of omega, resulted in maximum recovery of activity. The omega-less RNA polymerase from omega-less strains recruits the chaperonin, GroEL (unlike the wild-type enzyme), suggesting a structural deformity of the mutant enzyme. The GroEL-containing core RNA polymerase interacts efficiently with sigma70 to generate the fully functional holoenzyme. However, when GroEL was removed, the enzyme was irreversibly nonfunctional and was unable to bind to sigma70. The damaged enzyme regained activity after going through a cycle of denaturation and reconstitution in the presence of omega or GroEL. GroES was found to have an inhibitory effect on the core-sigma70 association unlike the omega subunit. The omega subunit may therefore be needed for stabilization of the structure of RNA polymerase.

Bacterial Proteins↗
PubMed1997

Surface-Enhanced Raman Spectroscopic Study of Isomeric Formylthiophenes in Silver Colloid

Surface enhanced Raman (SER) spectra of 2- and 3-formylthiophenes (2FT and 3FT) in silver colloids are compared with their normal Raman spectra in bulk and in acetonitrile solution. Experimental results indicate adsorption of 2FT on metal surface through the sulfur and the oxygen atoms with the ring plane vertical to the metal surface, whereas the ring plane of the 3FT molecule is inclined to the surface. Moreover, the SER spectrum of 2FT molecule predicts the existence of syn-form of this molecule in the adsorbed state because of large enhancement of the carbonyl stretching mode. Concentration dependence of relative enhancement infers the monolayer formation on metal surface at a specific concentration, implying strong evidence of chemisorption of the adsorbates. The excitation profile of C identical withC symmetric stretching mode of 2FT suggests classical plasmon resonance as the main contributor to surface enhancement. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Studies on the omega subunit of Escherichia coli RNA polymerase--its role in the recovery of denatured enzyme activity.

Highly purified Escherichia coli RNA polymerase contains a small subunit termed omega that has a molecular mass of 10,105 Da and is comprised of 91 amino acids. To elucidate the function of omega, whose role is as yet undefined, the subunit was purified to over 95% purity from an overproducing strain [BL21 (pGP1-2, pE3C-2)]. Purified omega was then reconstituted with RNA polymerase isolated from an omega-less mutant. Externally added omega inhibited promoter-specific transcriptional activity at all promoters tested. Renaturation of fully denatured omega-less RNA polymerase in the presence of excess omega yielded maximum recovery of activity suggesting a structural rather than functional role for omega.

DNA-Directed RNA Polymerases↗