Anti-urolithiatic effect of ethanolic extract of Pedalium murex linn. fruits on ethylene glycol-induced renal calculi.

PURPOSE: To evaluate effect of ethanolic extract of Pedalium murex Linn. fruits on experimental model of calcium oxalate nephrolithiasis. MATERIALS AND METHODS: Thirty-six male Wistar albino rats were randomly divided in 6 groups.Normal controls received distilled water for 28 days. Other five groups received ethylene glycol(1% v/v) in distilled water for 28 days. Pedalium murex ethanolic extract was given 200 mg/kg and 400 mg/kg orally in distilled water for 28 days in prophylactic groups (III and IV) and from 15th to 28th days in treatment groups (V and VI). The urea, creatinine, random blood sugar, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin and calcium were measured on 28th day. 24 hr urinary oxalate and volume were measured on day 0 and 28. On day 28, kidneys were removed, weighed and subjected to histopathological examination. Calcium oxalate crystallization was evaluated by renal histopathology and in-vitro method of mineralization.All parameters were analyzed by Kruskal-Wallis or one-way ANOVA with post-hoc test. RESULTS: Pedalium murex showed significant improvement in renal function and kidney weight inprophylactic groups as compared to ethylene glycol controls. It did not show any effect on urinary oxalate, urine volume and any other serological parameters. Calcium oxalate crystallization was significantly reduced in all the Pedalium murex treated groups (P < .05). Calcium oxalate and phosphate mineralization were also inhibited by 33% and 57%. CONCLUSION: Ethanolic extract of Pedalium murex fruits possess significant activity for prevention of renal calculi.

Evaluation of anti-inflammatory, analgesic, and antipyretic effects of ethanolic extract of Pedalium murex Linn. fruits.

This study investigated the possible anti-inflammatory, analgesic, and antipyretic effects of ethanolic extract of Pedalium murex Linn. fruits in selected experimental animal models. Anti-inflammatory activity of Pedalium murex Linn., with doses of 200 mg/kg and 400 mg/kg, p.o., was evaluated by Lambda-carrageenan induced paw oedema in Wistar albino rats; analgesic activity with doses of 280 mg/kg and 560 mg/kg, p.o., was evaluated by hot plate method and acetic acid induced writhing method in Swiss albino mice; and antipyretic activity with doses of 110 mg/kg and 220 mg/kg, p.o., was evaluated in New Zealand white rabbits by injecting gram -ve lipopolysaccharide obtained from E. coli. Results were analysed by one way ANOVA followed by Dunnet's multiple comparison test. Pedalium murex Linn. showed significant anti-inflammatory activity from 15 min to 180 min as compared to vehicle treated animals. It was comparable to diclofenac sodium at 180 min. The extract did not prolong the reaction time on hot plate method but significantly reduced the number of writhing after acetic acid administration. Also the extract did not show any antipyretic activity on lipopolysaccharide induced pyrexia. It is therefore concluded that the ethanolic extract of Pedalium murex Linn. fruits has an anti-inflammatory and peripheral analgesic effects.

Drug utilization pattern in critical care unit in a tertiary care teaching hospital in India.

AIMS: The aim of this study is to evaluate the drug utilization pattern and pharmacoeconomic analysis in critical care unit (CCU). MATERIALS AND METHODS: Indoor case papers of patients admitted in CCU between January 2008 and December 2010 were analyzed for demographic variables; indications; duration of CCU stay; proportion of common drugs used. Use of antimicrobials was evaluated based on the culture report and empirical regimen used. Defined daily dose (DDD)/100 bed-days were calculated. Various World Health Organization prescribing indicators were evaluated. Cost of drugs was calculated from Indian Drug Review (2010). RESULTS: A total of 397 cases were evaluated with a mean age of 44.62 years (95% confidence interval [CI]: 42.56-46.69). Average duration of CCU stay was 4.15 days (95% CI: 3.79-4.51). The average number of drugs prescribed per patient was 13.54 (95% CI: 13.05-14.04). Total drug utilization in terms of DDD/100 bed-days was 226.27. Metronidazole, cefotaxime, atropine, adrenaline, dopamine, dobutamine, deriphyllin, ranitidine, metoclopramide and furosemide were prescribed in more than 30% cases. Number of antimicrobials prescribed per patient was 2.50 (95% CI: 2.37-2.66). Cefotaxime + metronidazole (26.70%) were the most common empirical regimen used. Average cost of treatment per patient was Rs 3225.70 (95% CI: 2749.8-3701.6). Higher economic burden was noted among expired patients and admitted due to medical + surgical indication (P < 0.05). CONCLUSION: Poly-pharmacy and use of antimicrobials without culture report is a common problem in CCU.

Stavudine induced acute necrotizing pancreatitis with tetany in a pediatric patient.

A nine year old female patient presented with complaints of severe colicky abdominal pain, vomiting, and tingling with numbness for 3 days. Acute necrotizing pancreatitis associated with tetany due to anti-retroviral therapy was diagnosed. Stavudine was the probable causal agent. Unfortunately, the patient died due to severity of the reaction. High index of suspicion and early withdrawal of the offending drug may prevent further harm in such cases.

Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction.

A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus (DPT) vaccine used for routine immunization. Postreaction computed tomography (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries.

Toxic epidermal necrolysis due to lamotrigine in a pediatric patient.

A 12-year-male child developed toxic epidermal necrolysis (TEN) probably due to lamotrigine. The patient was on antiepileptic therapy (sodium valproate and clonazepam) since 6-7 months, and lamotrigine was added in the regimen 1-2 months back. A serious cutaneous reaction is more likely to occur during the first 2 months of starting lamotrigine. The use of lamotrigine as an add-on to valproate may have precipitated the reaction. Other drugs were ruled out based on the incubation period of TEN. Drug interactions should be kept in mind with multiple antiepileptic therapies. The patient died because of the severity of reactions and delay in starting the treatment with steroids. One must be vigilant in early detection of the reaction.

Effect of serum withdrawal on the contribution of L-type calcium channels (CaV1.2) to intracellular Ca2+ responses and chemotaxis in cultured human vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) chemotaxis is fundamental to atherosclerosis and intimal hyperplasia. An increase in intracellular Ca2+ [Ca2+]i is an important signal in chemotaxis, but the role of L-type calcium channels (CaV1.2) in this response in human vascular smooth muscle cells (hVSMC) has not been examined. hVSMC were grown from explant cultures of saphenous vein. Confluent hVSMC at passage 3 were studied after culture in medium containing 15% foetal calf serum (FCS) (randomly cycling) or following serum deprivation for up to 7 days. Smooth muscle alpha-actin was measured by immunoblotting and immunofluorescence microscopy. [Ca2+]i was measured using fura 2 fluorimetry. Chemotaxis was measured using a modified Boyden chamber technique and cell attachment to gelatin-coated plates was also quantified. The number and affinity of dihydropyridine-binding sites was assessed using [5-methyl-3H]PN 200-110 binding. In randomly cycling cells, the calcium channel agonist, Bay K 8644a and 100 mM KCl did not affect [Ca2+]i. In addition, the rise in [Ca2+]i induced by platelet-derived growth factor-BB (PDGF) was unaffected by the CaV1.2 antagonists, amlodipine and verapamil. In randomly cycling cells amlodipine did not affect PDGF-induced migration. In serum-deprived cells, smooth muscle alpha-actin was increased and Bay K 8644a and 100 mM KCl increased [Ca2+]i. PDGF-induced rises in [Ca2+]i were also inhibited by amlodipine and verapamil. The ability of Bay K 8644a to increase [Ca2+]i and verapamil to inhibit PDGF-induced rises in [Ca2+]i was evident within 3 days after serum withdrawal. In serum-deprived hVSMC Bay K 8644a induced chemotaxis and amlodipine inhibited PDGF-induced migration. Cell attachment in the presence of PDGF was unaffected by amlodipine in either randomly cycling or serum-deprived hVSMC. Serum withdrawal was associated with a decrease in the maximum number of dihydropyridine-binding sites (B(max)) and a decrease in affinity (K(D)). Serum deprivation of hVSMC results in increased expression of smooth muscle alpha-actin, a marker of more differentiated status, and increased [Ca2+]i responses and chemotaxis mediated by CaV1.2. These observations may have important implications for understanding the therapeutic benefits of calcium channel antagonists in cardiovascular disease.

PDGF stimulates DNA synthesis in human vascular smooth muscle cells via a novel wortmannin-insensitive phosphatidylinositol 3-kinase.

The class 1(A) phosphatidylinositol 3-kinase enzymes consist of a number of heterodimeric complexes of regulatory and catalytic subunits and have been implicated in a number of cellular responses. While platelet-derived growth factor (PDGF)-induced chemotaxis of human vascular smooth muscle cells (HVSMC) is inhibited by both wortmannin and LY294002, DNA synthesis is only inhibited by LY294002. Serum-induced DNA synthesis however is inhibited by LY294002, wortmannin and rapamycin. Similarly PDGF-induced protein kinase B (PKB) activation is inhibited by LY294002 but not by wortmannin or rapamycin. In conclusion PDGF-induced DNA synthesis appears to occur through a phosphatidylinositol 3-kinase (PI3-K)-dependent, but wortmannin-insensitive, PKB/Akt pathway.

Thrombospondin-1 differentially induces chemotaxis and DNA synthesis of human venous smooth muscle cells at the receptor-binding level.

Thrombospondin-1 is a large matricellular protein that acts as a pleiotropic growth factor for human vascular smooth muscle cells, and may play a role in the progression of vascular disease. Although we have previously demonstrated the dependence of both thrombospondin-1-stimulated cell chemotaxis and proliferation on tyrosine kinases, the receptor mechanisms involved remain obscure. This investigation aims to determine the nature of the receptor(s) involved in the cellular responses to thrombospondin-1. Cellular signals were identified by western blotting following cell stimulation, while cellular responses were assessed by measuring DNA synthesis and chemotaxis. These data demonstrate that thrombospondin-1-induced cell chemotaxis can be inhibited by a peptide containing the Arg-Gly-Asp motif, a function-blocking alpha(v)beta(3) antibody, a function-blocking integrin-associated protein (IAP) antibody and pertussis toxin, while thrombospondin-1-stimulated DNA synthesis is inhibited by a function-blocking alpha(3)beta(1) antibody. Similarly the Arg-Gly-Asp-containing peptide inhibits tyrosine phosphorylation of focal adhesion kinase and the p85 regulatory subunit of phosphatidylinositol 3-kinase, but does not significantly affect tyrosine phosphorylation, or activation, of extracellular-regulated kinase. These data suggest that soluble thrombospondin-1 interacts with human vascular smooth muscle cells via two independent and separable receptor-binding sites, to differentially stimulate cell chemotaxis and DNA synthesis.

The antimitogenic action of the sulphated polysaccharide fucoidan differs from heparin in human vascular smooth muscle cells.

The sulphated polysaccharides fucoidan and heparin both inhibit vascular smooth muscle cell (VSMC) proliferation. In this study we compared their actions on mitogenesis and ERK1/ERK2 activation in human VSMC. Although they displaced cell surface [3H]-heparin binding with similar affinity, they exerted clearly distinguishable actions. Fucoidan potently inhibited DNA synthesis stimulated by foetal calf serum, PDGF-BB and thrombospondin-1. Heparin inhibited the mitogenic action of serum and thrombospondin- I (though less potently than fucoidan), but failed to inhibit PDGF-BB-induced DNA synthesis. In parallel studies, fucoidan, but not heparin, inhibited ERK1/ERK2 activation by PDGF-BB. Moreover, fucoidan inhibited serum-induced mitogenesis in "heparin resistant" VSMC, which are refractory to heparin's antimitogenic action. In summary, the structurally different polysaccharides, heparin, fucoidan (and fucans) have distinguishable effects on mitogenesis and ERK1/ERK2 activation, suggesting that different mechanism(s) mediate these actions. The potent antimitogenic action of fucoidan and its efficacy in heparin resistant VSMC emphasise the need to further investigate its mechanism of action in human VSMC and suggest this agent could have therapeutic potential.