Search PubMed⌕ Search

Biomedical subjects

S Kapur

Publications and source records attributed to S Kapur.

At least 19 recordsLinked to original sources
PubMed2006

Spinal cord stimulation for relief of abdominal pain in two patients with familial Mediterranean fever.

Familial Mediterranean fever is a hereditary disease characterized by recurrent attacks of fever and serosal inflammation that commonly presents as severe abdominal pain. Though colchicine remains the mainstay of treatment, a significant proportion of patients are partially responsive, unresponsive or intolerant to it. We present two such cases where spinal cord stimulation (SCS) was used to manage the paroxysmal abdominal pain associated with this disease. Abdominal visceral pain pathways and the application of SCS techniques in its management are discussed.

Abdominal Pain↗
PubMed2005

The role of prophylactic oophorectomy in women undergoing surgery for colorectal cancer.

BACKGROUND: Current gynaecological practice is to remove surgically accessible ovaries with prior consent in post menopausal women to eradicate the risk of subsequent development of ovarian cancer. However in colorectal surgery opinion is divided, although evidence suggests that ovarian metastases from colorectal adenocarcinoma occur in 3-4% of cases. METHODS: The review is based on published literature of the role of prophylactic oophrectomy in women undergoing surgery for colorectal cancer, obtained from Medline/PubMed and other online databases using the terms 'prophylactic oophorectomy' and 'colon cancer'. Additional references were sourced by manually searching bibliographies of articles located. RESULTS AND CONCLUSION: There is a paucity of published information and published reports have conflicting conclusions. A preliminary report of a randomised prospective trial suggests the probability of increased recurrence free survival in the oophorectomy group. It would seem appropriate to consider the necessity and possible benefits of oophorectomy in women prior to surgery for colorectal cancer. This would seem particularly relevant in distal sigmoid or upper rectal cancers when the ovaries or uterus may be directly invaded and curative surgery would involve en bloc resection. Post menopausal women with a family history of ovarian cancer should be advised to have oophorectomy.

Adenocarcinoma↗
PubMed2004

Pushing the envelope in renal preservation; improved results with novel perfusate modifications for pulsatile machine perfusion of cadaver kidneys.

INTRODUCTION: Novel preservation techniques may diminish ischemia/reperfusion (I/R) injury. Our preservation laboratory has modified Belzer MPS for machine perfusion (MP) with prostaglandin E1 (PGE 1), nitroglycerin (NTG), and polyethylene glycol-superoxide dismutase (PEG-SOD) to attenuate I/R injury. We reviewed our recent experience using this novel formulation (NF) compared with standard perfusates. RESULTS: Between January 1998 and March 2000, 1060 consecutive kidneys were preserved in our laboratory. One hundred forty-eight kidneys (14%) were discarded. Fifty-eight percent of kidneys during this time period underwent MP (n = 532). En bloc kidney pairs were randomly assigned to pulsatile MP using Waters RM3 or MOX-100 perfusion systems using 1 of 3 perfusates; NF (NF; n = 119), Belzer MPS (MPS; n = 201), or Belzer II albumin gluconate (ALB; n = 212) Significant improvements in delayed graft function (DGF) rate were seen with NF versus other perfusates (8% vs 14% vs 19%, respectively; P =.03). At 6 months, graft survival was significantly improved with NF compared with MPS and ALB (96% vs 90% vs 87%, respectively; P =.03). NF also produced a significantly higher percentage of recipients with a serum creatinine level < or = 1.5 mg/dL. CONCLUSIONS: Novel modifications of standard MP perfusate improved outcomes after renal transplantation. Preservation-based interventions targeted to ameliorate I/R injury can improve outcomes and may allow expansion of the donor pool.

Adult↗
PubMed2003

In vivo evidence for dopamine-mediated internalization of D2-receptors after amphetamine: differential findings with [3H]raclopride versus [3H]spiperone.

Competition with endogenous dopamine (DA) is usually invoked to explain changes in [(11)C]raclopride binding observed after amphetamine administration in animals and humans. This account has recently been questioned because a number of inconsistencies have been reported that contradict it. In the present study, we investigated whether the decrease in [(3)H]raclopride binding observed in the rat striatum after an amphetamine challenge reflects true competition with endogenous DA or agonist-mediated internalization of D(2)-receptors. We found that the amphetamine-induced decrease in [(3)H]raclopride binding is caused by a decrease in D(2)-receptor density (B(max)) with no change in affinity (K(d)). In contrast, in the same tissue, neither the B(max) nor the K(d) were affected when measured with [(3)H]spiperone. Challenge with amphetamine not only decreased the number of D(2)-receptors but also eliminated the proportion (22%) of receptors usually in the high-affinity state. The addition of Gpp(NH)p had no effect on B(max), suggesting that these receptors were not just noncompetitively bound with dopamine at the cell-surface. Subcellular fractionation studies showed that amphetamine treatment led to a decrease in radioligand binding in the cell-surface fraction for both [(3)H]raclopride and [(3)H]spiperone; however, in the case of [(3)H]spiperone, this was accompanied by a compensatory increase in binding in the intracellular compartment, whereas no increase was seen with [(3)H]raclopride. These data suggest that amphetamine releases dopamine, which binds to the high-affinity state of the D(2)-receptor, leading to its sequestration in some intracellular compartment; in this compartment, sequestered receptors are inaccessible to [(3)H]raclopride binding but can still be bound by [(3)H]spiperone.

Amphetamine↗
PubMed2002

Dopamine D2 receptors internalize in their low-affinity state.

The present study was done in order to determine whether dopamine internalizes D2 receptors in CHO cells and whether the high-affinity or the low-affinity state of the dopamine D2 receptor is associated with dopamine-induced internalization of dopamine D2 receptors. Using [3H]sulpiride to label D2Long receptors in CHO cells, it was found that dopamine lowered the binding of [3H]sulpiride by 20%. Although the high-affinity states of D2 were converted to low-affinity states by guanine nucleotide, the latter had no effect in blocking the dopamine-induced reduction in [3H]sulpiride binding, indicating that the dopamine-induced internalization of D2 receptors occurred with D2 in the low-affinity state.

Animals↗
PubMed2002

Significant dissociation of brain and plasma kinetics with antipsychotics.

Current dosing regimens of psychotropic drugs are based on plasma kinetic considerations, although it is unclear whether plasma levels faithfully reflect brain kinetics of drugs.(1,2) To examine this, we compared the kinetics of plasma levels of two widely used antipsychotics, olanzapine and risperidone, vs the time course of their effects in the brain. We used positron emission tomography (PET) and [(11)C]-labeled ligands to quantify striatal and extra-striatal dopamine-2 (D(2)), and cortical serotonin-2A (5-HT(2A)) receptor occupancy in healthy subjects after a single dose, and in patients chronically treated for psychosis. We found a significant dissociation of brain and plasma kinetics. Mean plasma elimination half-lives of single doses of olanzapine and risperidone were 24.2 and 10.3 h, respectively, whereas it took on average 75.2 h with olanzapine, and 66.6 h with risperidone to decline to 50% of their peak striatal D(2) receptor occupancy. We found similar discrepancies between the time course of plasma levels and extra-striatal D(2) as well as 5-HT(2A) receptor occupancy. Our results question the current reliance on plasma kinetics as the main basis for dosing regimens of antipsychotics. Studies of brain kinetics may provide a sounder basis for determining dosing schedules of psychotropic medications.

Adult↗
PubMed2002

Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans.

The effect of endogenous dopamine (DA) on neostriatal DA D(1) and D(2) receptor binding potentials (D(1)RBP and D(2)RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [(11)C]SCH23390 and [(11)C]raclopride, respectively, by comparing the D(1)RBP and D(2)RBP before and after acute DA depletion. DA depletion was achieved by per-oral administration of 4500 mg alpha-methyl-para-tyrosine (AMPT) given in the 25 h prior to [(11)C]SCH23390 PET and of 5250 mg AMPT given in the 29 h prior to [(11)C]raclopride PET. Six healthy subjects completed the protocol. The AMPT treatment decreased plasma levels of the DA metabolite homovanillic acid by 61 +/- 16% (4500 mg; average +/- standard deviation) and 62 +/- 17% (5250 mg), and levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol by 58 +/- 7% (4500 mg) and 66 +/- 5% (5250 mg). This AMPT treatment increased D(2)RBP significantly from 3.18 +/- 0.34 to 3.59 +/- 0.30 but no significant change was observed in D(1)RBP (1.64 +/- 0.24 pre AMPT vs 1.70 +/- 0.17 post AMPT). Thus, while DA depletion "uncovers" D(2)receptors, it does not do so for D(1) receptors. The implications of this finding for measuring endogenous DA and its effects on in vivo receptor binding in humans are discussed.

Administration, Oral↗
PubMed2002

NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia.

Ketamine and PCP are commonly used as selective NMDA receptor antagonists to model the putative hypoglutamate state of schizophrenia and to test new antipsychotics. Recent findings question the NMDA receptor selectivity of these agents. To examine this further, we measured the affinity of ketamine and PCP for the high-affinity states of the dopamine D(2) and serotonin 5-HT(2) receptor and found that ketamine shows very similar affinity at the NMDA receptor and D(2) sites with a slightly lower affinity for 5-HT(2) (0.5 microM, 0.5 microM and 15 microM respectively), while PCP shows similar affinity for the NMDA and 5-HT(2) sites, with a slightly lower affinity for the D(2) site (2 microM, 5 microM and 37 microM respectively). Further, ketamine and PCP in clinically relevant doses caused a significant increase in the incorporation of [(35)S]GTP-gamma-S binding in CHO-cells expressing D(2) receptors, which was prevented by raclopride, suggesting a partial agonist effect at the D(2) receptor. Thus, ketamine and PCP may not produce a selective hypoglutamate state, but more likely produce a non-selective multi-system neurochemical perturbation via direct and indirect effects. These findings confound the inferences one can draw from the ketamine/PCP models of schizophrenia.

Animals↗
PubMed2002

The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats.

All atypical antipsychotics avoid extrapyramidal side-effects yet differ in their propensity to cause other side-effects, like prolactin elevation. We proposed that the atypical antipsychotics with a propensity for prolactin elevation would show a higher pituitary versus striatal D2 receptor occupancy. To investigate this hypothesis, we tested four atypical antipsychotics, two that are commonly associated with prolactin elevation (amisulpride and risperidone) and two that are less frequently associated (quetiapine and olanzapine). In particular, we calculated their ED(50) values to increase plasma prolactin and block peripheral pituitary D2 receptors to their ED(50) values to antagonize apomorphine-induced stereotypy and occupy central striatal D2 receptors. All antipsychotics dose dependently increased prolactin levels and antagonized apomorphine-induced stereotypy. However, the central to peripheral potency (ED(50) for apomorphine antagonism to ED(50) for prolactin elevation) differed remarkably across these drugs: amisulpride (21764), risperidone (14), quetiapine (10), and olanzapine (1.7). Compounds displaying a higher peripheral potency brought about higher prolactin levels for a given level of functional central antagonism. This dissociation between central and peripheral effects was explained by the differential occupancy of D2 receptors in the striatum versus in the pituitary [ratio of striatal/pituitary ED(50) values (milligram per kilogram) for D2 occupancy): amisulpride (17/0.026 = 654), risperidone (0.89/0.081 = 14), quetiapine (24/4.1 = 6), olanzapine (0.30/0.43 = 0.7). These results indicate that dissociation between central and peripheral D2 receptor occupancy is a major determinant of the degree of prolactin elevation observed at therapeutic doses.

Animals↗
PubMed2001

Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient.

"Atypical" antipsychotics are associated with a much lower propensity for extrapyramidal side effects and, with some exceptions, a lack of sustained prolactin elevation. The authors propose that a low-affinity and fast dissociation (in molecular terms) from the dopamine D(2) receptor, along with administration of the drug in doses that lead to appropriate levels of dopamine D(2) receptor blockade, are the most important requirements for atypicality. Actions at other receptors (5-HT(2), D(4), etc.) may not be necessary to achieve atypicality, and while action at these receptors may have benefits on symptoms such as mood and cognition, this is as yet to be conclusively proven. Why clozapine is effective in refractory patients is still elusive and efforts to make antipsychotics that are devoid of effects on the dopamine D(2) receptors so far have been unsuccessful. In light of this, the authors provide a heuristic model linking pathophysiology and therapeutics and suggest that the ideal treatment for schizophrenia is unlikely to be single-drug with multireceptor blockade (a sort of one-size-fits-all polypharmacy) but will require several specific and targeted treatment strategies that are titrated to match the variable expression of different dimensions of schizophrenia in each patient.

Amisulpride↗
PubMed2001

Radical toxicity of phenols: a reference point for obtaining perspective in the formulation of QSAR.

In this report we discuss some of the surprising ways phenols interact in vivo and how some of their toxic activity can be understood in terms of QSAR and in fact can be related via electronic terms to be similar to processes of simple chemical reactions. A simple two-term QSAR is found to be a good predictor of estrogenic toxicity. However, it is also shown that even the simplest of phenols can yield quite unexpected results than can be elucidated via QSAR. We still have a long way to go before we can predict under what conditions a phenol will produce toxic effects such as cancer and how much phytophenols one can consume before reaping a toxic reaction.

Free Radicals↗