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Biomedical subjects

N Sridhar

Publications and source records attributed to N Sridhar.

12 recordsLinked to original sources

Early and severe hyperparathyroidism associated with hypercalcemia after renal transplant treated with cinacalcet.

Bone disease is a common clinical problem following renal transplantation. In renal transplant recipients, multiple underlying factors determine the extent of bone loss and the subsequent risk of fractures. In addition to the well-recognized risk to bone disease posed by steroids, calcineurin inhibitors and pre-existing bone disease, persistent hyperparathyroidism (HPT) contributes to post-transplant bone loss. HPT is usually treated with vitamin D supplements combined with calcium. Patients whose HPT is associated with hypercalcemia pose a difficult therapeutic dilemma which often requires parathyroidectomy. Cinacalcet, a calcium mimetic agent, offers a unique pharmacologic approach to the treatment of patients with post-transplant hypercalcemia and HPT. In this paper, we describe the clinical course and biochemical changes in 10 renal transplant recipients with hypercalcemia and severe HPT early after renal transplantation treated with cinacalcet. Cinacalcet therapy corrected hypercalcemia and decreased parathyroid hormone (PTH) levels in all cases. A transient rise in the level of alkaline phosphatase was noted following initiation of cinacalcet therapy. In this patient population, correction of HPT was not permanent as discontinuing cinacalcet therapy led to a rapid rise in PTH level.

Administration, Oral↗

In vitro pharmacological investigations of Sapindus trifoliatus in various migraine targets.

Phytotherapies have offered alternative sources of therapy for migraine and gained much importance in prophylactic treatment. The aqueous extract of pericarp of fruits of Sapindus trifoliatus Linn (ST), family Sapindaceae was evaluated for its affinity for 5-HT(1B/1D) receptors in rabbit saphenous vein, alpha-adrenoceptors in rabbit aorta, GABA receptors in guinea pig ileum, 5-HT(2B) receptors in rat fundus and vanilloid receptors in guinea pig trachea. The calcium blocking effect was studied in rabbit aorta while the modulatory role of ST on platelet serotonin release was evaluated in human platelets. The aqueous extract of Sapindus trifoliatus exhibited significant 5-HT(2B) receptor inhibition and moderate platelet serotonin release inhibition.

Adult↗

5-HT3 receptors in selective animal models of cognition.

Role of 5-HT3 receptors in cholinergic hypofunctional models of cognitive impairment in the elevated plus maze model and a passive avoidance model is studied. Cognitive impairment was caused by scopolamine (1 mg/kg, ip) in mice and 5-HT3 ligands mCPBG (1 and 5 mg/kg, ip) and ondansetron (0.5 and 5 mg/kg, ip) were administered before the pre-learning phase to study the effects on acquisition, while post-learning administration was used to determine the effects on consolidation. Ondansetron improved acquisition and retention in cholinergic hypofunctional models while mCPBG potentiated selected impaired cognitive indices. The results indicate the role of 5-HT3 receptors in cognition and that an ideal evaluation of 5-HT3 ligands in cognition should distinguish true cognitive effects from locomotor, motivational and emotional effects.

Animals↗

Synthesis of new arylaminoquinoxalines and their antimalarial activity in mice.

2-Arylaminoquinoxalines were prepared by the condensation of 2-chloroquinoxaline with the appropriate Mannich bases in the presence of HCl. To synthesize the Mannich bases, 4-acetamidophenol was reacted with formaldehyde and dialkylamine to yield 3-[(dialkylamino) methyl]-4-hydroxyacetanilide, followed by hydrolysis. Antimalarial activities of the new arylaminoquinoxalines were evaluated against the rodent malaria parasite Plasmodium yoelii at a dose of 75 mg kg(-1). Three compounds synthesized (2-[3-[(diethylamino) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2b), 2-[3-[(pyrrolidinyl) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2f), and 2-[3-[(piperidinyl) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2g)) showed moderate antimalarial activity.

Animals↗

A pilot study of twin dialyzers in parallel to enhance delivered KT/V.

BACKGROUND: Adequacy of delivered dialysis is important in preventing morbidity in patients on hemodialysis for end-stage renal disease. A satisfactory KT/V is often difficult to obtain in patients with a large body mass despite optimization of remediable factors. AIM: This pilot study was performed to examine the hypothesis that twin dialyzers in parallel enhance delivered KT/V. METHODS: Three compliant patients on maintenance hemodialysis with post-dialysis weights greater than 95 kg who had a KT/V between 1.0 and 1.3 despite optimization of duration of dialysis, blood flow rates and anticoagulation and absence of access recirculation were studied using twin dialyzers in parallel after in vitro experiments demonstrated the safety of this technique. After a run-in period lasting over six months, during which the technique was perfected, three study treatments with twin dialyzers were compared to three treatments before and three treatments after study treatments. Both study and control treatments were performed under identical, rigidly standardized conditions. There was a wash-out period before the control and the study treatments. KT/V was calculated using the post-dialysis blood urea nitrogen (BUN) obtained by the stop-flow technique. RESULTS: KT/V was higher with twin dialyzers in parallel than with single dialyzers (mean +/- SD 1.54 +/- 0.32 for twin dialyzers vs 1.33 +/- 0.11 for single dialyzers) despite the lack of significant differences in potentially confounding variables. CONCLUSIONS: Using twin dialyzers in parallel appears to enhance delivered KT/V and is a safe and potentially useful technique especially in patients with a large body mass.

Body Mass Index↗

Synthesis and preliminary pharmacological investigations of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine derivatives as potential atypical antipsychotic agents in mice.

In research towards the development of new atypical antipsychotic agents, one strategy is that the dopaminergic system can be modulated through manipulation of the serotonergic system. The synthesis and preliminary pharmacological evaluation of a series of potential atypical antipsychotic agents based on the structure of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine (7) is described. Compound 7e, 5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]ethyl}-2,3-dihy dro-1H- indol-2-one, from this series showed significant affinities at the 5-HT1A and 5-HT2A receptors and moderate affinity at the D2 receptor. 7e exhibits a high reversal of catalepsy induced by haloperidol indicating its atypical antipsychotic nature.

Animals↗

Nursery outbreak of neonatal fungal arthritis treated with fluconazole.

Eight preterm infants with mean gestational age of 31.6 +/- 1.16 weeks and a mean birth weight of 1310 +/- 201.7 g presented at a mean postnatal age of 26 +/- 11.4 days with knee joint swellings and pedal oedema. There was no other clinical, haematological or microbiological evidence of bacterial sepsis. Fungal cultures yielded growth of Candida spp. from blood in five, from urine in four, from cerebrospinal fluid in one, and from all the three babies in whom the joints were aspirated. Radiographic changes of metaphysitis of the involved joints were noted in all. All infants had received prior antibiotic therapy. No infant had received total parenteral nutrition or had central lines inserted. All infants were treated with fluconazole in doses of 7.5 mg/kg/day for 6 weeks. Six of eight were thriving well at 3 months of age without any evidence of residual joint disease. One infant succumbed to disseminated disease and one was lost to follow-up. Candidial arthritis is an uncommon presentation of neonatal candidiasis. Fluconazole therapy proved effective.

Antifungal Agents↗

Clinical correlations of cyclosporine-specific and -nonspecific assays in stable renal transplants, acute rejection, and cyclosporine nephrotoxicity.

Accurate and early diagnosis of the cause of renal transplant dysfunction is important in successful patient management. Controversy exists as to whether a cyclosporine-specific or -nonspecific method is more predictive of clinical events. In an attempt to answer this question, all episodes of acute renal dysfunction were reviewed in 322 stable renal transplant recipients over a 20-month period. To diagnose the cause of each episode of renal dysfunction, an analysis was made of patient demographics; weight; serum creatinine; cyclosporine dose; cyclosporine level, using a specific method--high-performance liquid chromatography (HPLC)--and a nonspecific method--fluorescent polarization immunoassay (FPIA); changes in cyclosporine dose; renal biopsy; and response to any therapeutic intervention. There were 138 patients, who developed 279 episodes of renal dysfunction. Causes of renal dysfunction were cyclosporine-related (n = 103), acute rejection (n = 63), extracellular fluid volume depletion (n = 27), other (n = 59), and unknown (n = 27). The mean HPLC cyclosporine level was significantly different in patients with acute cyclosporine toxicity (p < 0.001) and patients with acute rejection (p < 0.001) when compared to those with stable renal function; the mean FPIA cyclosporine levels were not significantly different between the three groups. However, a larger percentage of patients with rejection were subtherapeutic when measured by HPLC, while a higher proportion of patients with nephrotoxicity were above the therapeutic range measured by FPIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗