Protein S Deficiency and Arterial Thromboembolism: A Case Report and Review of the Literature.

Protein S (PS) deficiency is associated with a well documented risk of venous thromboembolism. However, the relation between PS deficiency itself to arterial thrombotic events (ATEs) is not clearly established. In our case, we report an ATE in a patient with a documented novel PROS1 mutation and a family history of PS deficiency. Other etiologies for arterial thrombosis were excluded. The role of precise diagnosis with levels of PS and documentation for mutational analysis are discussed. We highlight the problems with diagnosis in previously reported cases with arterial thrombotic events and discuss the potential for treatment with antiplatelet therapy in a subset of patients with PS deficiency.

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues.

BACKGROUND: Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. OBJECTIVE: The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. METHODS: Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. RESULTS: Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. CONCLUSION: The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.

RESUMO Contexto Anti-inflamatórios não esteroidais induzem lesões da mucosa gástrica devido às suas propriedades ácidas. Ranitidina, um antagonista dos receptores H2, revelou-se benéfico em pacientes com úlceras gástricas. Objetivo - O presente estudo foi realizado para avaliar o efeito da administração de ranitidina em gastropatia induzida por anti-inflamatórios não esteroidais (diclofenaco, nimesulida) e seu efeito sobre a histopatologia do estômago, dos rins e fígado. Métodos Diclofenaco, nimesulida e ranitidina foram administradas em doses de 2, 4 e 6 mg/kg, p.o. uma vez diariamente por 14 dias e seu efeito sobre o volume gástrico, acidez, significam o número de úlcera e o pH gástrico. Além disso, o exame histopatológico também foi realizado em seções do estômago, dos rins e fígado. Resultados Após a administração de diclofenaco ou nimesulida, todos os parâmetros gástricos foram significativamente alterados assim como a histopatologia do estômago, fígado e rim. No grupo controle, as seções renais mostraram glomérulos normais sem espessamento da membrana basal glomerular, enquanto em diclofenaco isolado, nimesulida isolado e grupos com ranitidina e nimesulida, foi observado espessamento da membrana basal glomerular. Estas alterações observou-se serem revertidas no grupo ranitidina com diclofenaco. As seções do fígado, o grupo controle mostrou placas e cordões de hepatócitos cuboidais anastomosados com núcleos bem demarcados e citoplasma abundante. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, leve dilatação dos sinusoides é vista acoplados com proeminência de veia central. Nos grupos diclofenaco e nimesulida sozinhos, túbulos proximais e distais contorcidos mostram necrose tubular focal leve. Nas secções gástricas, o grupo controle mostrou várias dobras formando vilosidades e a superfície do revestimento epitelial da mucosa. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, o duodeno mostrou dispersas células inflamatórias predominantemente compostas por linfócitos. Nos grupos diclofenaco e nimesulida sozinhos, as secções de áreas gástricas mostraram necrose parcial e inflamação crônica moderada respectivamente. Conclusão - O estudo, portanto, forneceu o fundamento terapêutico para administração simultânea de bloqueador de receptor H2 (ranitidina) com diclofenaco, sendo mais benéfica em comparação com ranitidina com nimesulida para minimizar a intolerância gástrica de diclofenaco no tratamento a longo prazo de condições inflamatórias.

Toxicological assessment of Ricinus communis Linn root extracts.

Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000 mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000 mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.

PCR amplification of the IS6110 insertion element of Mycobacterium tuberculosis in fecal samples from patients with intestinal tuberculosis.

PCR amplification of insertion element IS6110 of Mycobacterium tuberculosis in fecal samples was evaluated in the diagnosis of intestinal tuberculosis (ITB). The numbers of samples that tested positive by PCR with SalI digestion were 16/18 untreated-ITB samples, 0/8 treated-ITB samples, 12/14 smear-positive pulmonary tuberculosis samples, and 0/30 control samples. The sensitivity, specificity, positive predictive value, and negative predictive value of fecal PCR were 88.8%, 100%, 100%, and 93.7%, respectively.

Anti-inflammatory and free radical scavenging activity of Ricinus communis root extract.

Anti-inflammatory and free radical scavenging activities of the methanolic extract of Ricinus communis (RCM) (Euphorbiaceae) Linn. root was studied in Wistar albino rats. The methanolic extract at doses 250 and 500 mg/kg p.o. exhibited significant (P<0.001) anti-inflammatory activity in carrageenan-induced hind paw edema model. The extract at the dose of 500 mg/kg p.o. also exhibited significant (P<0.001) anti-inflammatory activity in cotton pellet granuloma model. The methanolic extract showed significant free radical scavenging activity by inhibiting lipid peroxidation initiated by carbon tetrachloride and ferrous sulphate in rat liver and kidney homogenates. The extract enhanced free radical scavenging activity of stable radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH*), nitric oxide and hydroxyl radical in in vitro assay methods. The results of the study indicate that the methanolic extract of Ricinus communis root possess significant anti-inflammatory activity in acute and chronic inflammatory models in rats. The observed pharmacological activity may be due to the presence of phytochemicals like flavonoids, alkaloids and tannins present in the plant extract with various biological activities.

Risk of colorectal cancer in ulcerative colitis in India.

BACKGROUND: The risk for colorectal cancer (CRC) in ulcerative colitis (UC) in India is not known. METHOD: Retrospective cohort from a tertiary level hospital in South India. Analysis of archived records of all patients with UC who underwent colonoscopy and segmental biopsies over the last 25 years. Incidence densities and risk of developing high grade dysplasia or CRC was calculated and chi-squared test was performed for risk factors of interest. RESULTS: Complete records were available for 532 patients, 336 (63.2%) male. The mean (+/- SEM) duration of illness was 6.04 +/- 0.29 years. In total, 234 patients (44%) had pancolitis, 121 (22.7%) had left-sided colitis and 177 (33.3%) had proctitis or proctosigmoiditis. Overall, five (0.94%) patients developed carcinoma and one (0.19%) patient had high grade dysplasia. The incidence density and risk of developing either CRC or high grade dysplasia was zero in the first 10 years of disease. In those with disease duration of 10-20 years, incidence density was 2.34 per 1000 person years' duration (PYD) for all patients with colitis and 4.5 per 1000 PYD for patients with pancolitis alone. This corresponded to risks of 2.3% and 4.4%, respectively. For those with disease duration longer than 20 years, incidence density was 2.73 per 1000 PYD for all patients and 4.9 per 1000 PYD for patients with pancolitis. This corresponded to risks of 5.8% and 10.2%, respectively. Duration of disease beyond 10 years and extent of colitis were the only risk factors significantly associated with CRC. CONCLUSIONS: The risk of developing CRC is Indian patients with UC is lower than that reported from the West. Strategies for cancer surveillance in Indian patients with UC need to be tailored accordingly.

Antioxidant activity of Thespesia populnea bark extracts against carbon tetrachloride-induced liver injury in rats.

Antioxidant activity of the aqueous (AET) and methanolic extracts (MET) of the Thespesia populnea bark was investigated in rats by inducing liver injury with carbon tetrachloride:olive oil (1:1). The extracts exhibited significant antioxidant activity showing increased levels of glutathione peroxidase (GPX), glutathione S-transferase (GST), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) and decreased level of lipid peroxidation (LPO). Thespesia populnea bark extracts, AET and MET, at a dose level of 500mg/kg showed significant antioxidant activity against carbon tetrachloride-induced liver injury in rats.