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Biomedical subjects

K Mukherjee

Publications and source records attributed to K Mukherjee.

At least 19 recordsLinked to original sources
PubMed2004

Influence of sweet tasting solutions on opioid withdrawal.

The effect of the ingestion of palatable fluids on the suppression of opioid withdrawals in the opioid-dependent rats was studied. Physical dependence was induced by administration of morphine over a period of 6 days. Withdrawals were precipitated with naloxone (1 mg/kg, s.c.) 4 h after the last morphine injection on the 6th day. Test drugs (10-30% sucrose solution) were given orally for 2 h prior to naloxone-induced withdrawal in 14 h water deprived rats. Somatic signs of withdrawals were scored by using the global Gellert-Holtzman rating scale. Animals pretreated with low doses of sucrose solution (10-15%) did not produce any effect on the global withdrawal scale whereas a significant decrease on the global withdrawal scores was observed at higher doses of sucrose solution (20-30%) as compared to the controls. All the individual behavioral signs of withdrawals were significantly suppressed in a dose-related manner at higher doses of sucrose solutions whereas minimal suppression was observed for facial fasciculation/teeth chattering. These findings provide support that ingestion of high concentrations of sucrose solutions for shorter duration may activate the endogenous opioid system and appears to have an important role in modifying morphine withdrawals.

Analysis of Variance↗
PubMed2003

A comparison of total intravenous with balanced anaesthesia for middle ear surgery: effects on postoperative nausea and vomiting, pain, and conditions of surgery.

We compared postoperative nausea and vomiting (PONV), pain and conditions for surgery in patients scheduled for middle ear surgery. In a double-blind study, 100 patients were randomly allocated to receive either balanced anaesthesia (group A) using fentanyl, propofol and isoflurane, or total intravenous anaesthesia (group B) using propofol and remifentanil infusions. Pain scores, nausea/vomiting scores, conditions for surgery and analgesic requirements were recorded for 18 h post operatively. In the recovery ward, patients in group B suffered significantly less PONV (p = 0.026) with a reduced requirement for anti-emetic medication (p = 0.023); however, this difference was not maintained on the ward. The overall incidence of PONV was 34% and 17% in groups A and B, respectively. Initial pain scores were higher in group B in the recovery ward (p = 0.003) and patients required more morphine administration (p = 0.002); however, pain scores were similar on the ward. Conditions for surgery were found to be better in group B.

Adult↗
PubMed2002

Hyperalgesic response in rats fed sucrose from weaning to adulthood: role of VMH.

The ventromedial nucleus of hypothalamus (VMH) is implicated in food intake, food preference, nociception and its modulation by palatable food. Palatable drink for 5-48 h in adult rat produced hyperalgesia, which is mediated by VMH. The effect of palatable dietary supplement after weaning on the nociceptive response in adult rats has not been reported. Whether or not VMH influences these nociceptive responses is also not known. The present study was therefore undertaken to investigate the effect of VMH lesion on the nociceptive responses in adult rats ingesting (ad libitum) sucrose from weaning. Weanling rats received sucrose solution in addition to drinking water and laboratory pellets (sucrose-fed group), while the control group of rats received laboratory pellets alone. On attaining adulthood, the behavioral responses, namely tail flick latency (TFL), thresholds of tail flick (TF), vocalization during stimulus (SV), and vocalization after discharge (VA) to phasic and formalin pain rating (FP) to tonic noxious stimuli, were noted in pre- and post-VMH lesion states of both groups of rats. In chronic sucrose-fed rats, the TFL was not affected, the thresholds of TF, SV and VA were significantly decreased (P<.001) and the FP was increased in comparison to the control group, suggesting a hyperalgesic response to chronic sucrose ingestion. After the VMH lesion, in sucrose-fed rats, the thresholds of TF, SV and VA remained unaltered, while the FP was attenuated and TFL decreased. In control rats, VMH lesion produced a hyperalgesic response to both the phasic and tonic noxious stimuli. The data indicate that chronic sucrose feeding and VMH lesion differentially affect the nociceptive responses to the phasic and tonic noxious stimuli. These results suggest that chronic sucrose feeding from weaning to adulthood produces hyperalgesia to both the tonic and phasic noxious stimuli (except TFL), which is probably mediated by VMH.

Animals↗
PubMed2001

SopE acts as an Rab5-specific nucleotide exchange factor and recruits non-prenylated Rab5 on Salmonella-containing phagosomes to promote fusion with early endosomes.

Rab-GTPase regulates the fusion between two specific vesicles. It is well documented that, for their biological function, Rab proteins need to be prenylated for attachment to the vesicle membrane. In contrast, we showed in the present investigation that SopE, a type III secretory protein of Salmonella, translocates onto Salmonella-containing phagosomes (LSP) and mediates the recruitment of non-prenylated Rab5 (Rab5:DeltaC4) on LSP in GTP form. Simultaneously, SopE present in infected cell cytosol acts as an Rab5-specific exchange factor and converts the inactive Rab-GDP to the GTP form. The non-prenylated Rab5 subsequently promoted efficient fusion of LSP with early endosomes. This is the first demonstration that a prenylation-deficient Rab protein retains biological activity and can promote vesicle fusion, if it is recruited on the membrane by some other method.

Animals↗
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

Identification of a critical lysine residue at the active site in glyceraldehyde-3-phosphate dehydrogenase of Ehrlich ascites carcinoma cell. Comparison with the rabbit muscle enzyme.

The involvement of the lysine residue present at the active site of Ehrlich ascites carcinoma (EAC) cell glyceraldehyde-3-phosphate dehydrogenase (Gra3PDH) was investigated by using the lysine specific reagents trinitrobenzenesulfonic acid (TNBS) and pyridoxal phosphate (PP). Both TNBS and PP inactivated EAC cell Gra3PDH with pseudo-first-order kinetics with the rate dependent on modifier concentration. Kinetic analysis, including a Tsou plot, indicated that both TNBS and PP apparently react with one lysine residue per enzyme molecule. Two of the substrates, d-glyceraldehyde-3-phosphate and NAD, and also NADH, the product and competitive inhibitor, almost completely protected the enzyme from inactivation by TNBS. A comparative study of Gra3PDH of EAC cell and rabbit muscle indicates that the nature of active site of the enzyme is significantly different in these two cells. A double inhibition study using 5,5'-dithiobis(2-nitrobenzoic acid) and TNBS and subsequent reactivation of only the rabbit muscle enzyme by dithiothreitol suggested that a cysteine residue of this enzyme possibly reacts with TNBS. These studies on the other hand, confirm that an essential lysine residue is involved in the catalytic activity of the EAC cell enzyme. This difference in the nature of the active site of EAC cell Gra3PDH that may be related to the high glycolysis of malignant cells has been discussed.

Amino Acid Sequence↗
PubMed2001

Adenotonsillectomy in children: a comparison of morphine and fentanyl for peri-operative analgesia.

This study compared the effectiveness and side-effects of intra-operative fentanyl with fentanyl and morphine for elective adenotonsillectomy in a double-blind study, in 60 children randomly allocated to receive either intravenous fentanyl 1 microg x kg(-1) intra-operatively or intramuscular morphine 100 microg x kg(-1) at induction. All children received a standard anaesthetic induction with intravenous fentanyl 1 microg x kg(-1) and propofol 4-5 mg x kg(-1) and maintenance with oxygen, nitrous oxide and isoflurane. Pain scores, emetic episodes and supplemental morphine requirements were recorded for 24 h postoperatively. The overall incidence of postoperative vomiting was high in both groups: 70% in the fentanyl group and 78% in the morphine group. The incidence of postoperative vomiting was lower in the fentanyl group (p < 0.03) in the first 4 h, but similar by 24 h. Children who received morphine at any time in the first 24 h had more median (range) episodes of vomiting [2 (0-7)] than children receiving fentanyl only [l (0-3); p < 0.03]. Administration of rescue anti-emetics, pain scores in recovery and pain scores over the next 24 h were similar between the two groups.

Adenoidectomy↗
PubMed2001

Urinary stress incontinence in obese women: tension-free vaginal tape is the answer.

OBJECTIVE: To determine the effectiveness of the tension-free vaginal tape (TVT) in obese women with genuine stress incontinence (GSI), in whom obesity is often considered a relative contraindication to surgical treatment by traditional approaches, e.g. Burch colposuspension and slings (which are difficult and carry increased morbidity) or injectable agents (which although simple, are unpredictable and expensive). PATIENTS AND METHODS: Data on 242 consecutive women with urodynamically proven GSI were collected prospectively. The women were subdivided into three groups with a body mass index (BMI) of < 25, 25-29 and >or=30; obesity was defined as a BMI of >or=30. All procedures were performed under spinal anaesthesia. The King's validated quality of life (QoL) questionnaires (version 7) were completed before and 6 months after surgery. The subjective results were defined as a cure, significant improvement or failure. RESULTS: Almost 90% of the obese women with GSI were cured, while the remaining 10% noted a considerable improvement in their symptoms. There was no significant difference in cure rates among the three groups. There was a highly significant (P < 0.001) improvement in QoL in all groups. CONCLUSION: The TVT is at least as effective in obese women as in those with a lower BMI. The TVT is a simple and minimally invasive procedure, with low morbidity even in the obese group. TVT can be offered confidently to all obese women with GSI.

Adult↗
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↗