Comparative evaluation of ulcer prevention efficacy of orally, rectally and sublingually administered omeprazole in three acute gastric ulcer models in rats

Summary— Ulcer prevention efficacy of orally, rectally and sublingually administered omeprazole was evaluated and compared using ulcer index and percentage inhibition of ulcerogenecity in three different acute gastric ulcer models viz, indomethacin, 0.6N HCl and aspirin (after pylorus ligation) induced ulcers in rats. The ulcer prevention efficacy after oral, rectal and sublingual administration were statistically significant ( P < 0.01) in all the models. The differences in ulcer index and percentage inhibition of ulcerogenecity for rectal and sublingual administration were insignificant ( P < 0.05) in indomethacin and HCl induced ulcers and were significant ( P < 0.05) in aspirin induced ulcers. The ulcer prevention activity was significantly higher ( P < 0.05) after rectal and sublingual routes when compared to oral administration in all three models evaluated. Results revealed a faster onset and higher extent of pharmacodynamic activity of omeprazole after rectal and sublingual administration.     

Host microenvironment in breast cancer development: Extracellular matrix–stromal cell contribution to neoplastic phenotype of epithelial cells in the breast

Epithelial–mesenchymal interactions play an important role both in normal mammary gland development and during neoplastic transformation. Perturbations in the production, deposition and degradation of the extracellular matrix occurring during neoplastic transformation and progression have been implicated to arise from alterations in the stromal response. These changes in the stroma exhibit a dominant regulatory role, via microenvironmental epigenetic effectors, to contribute to the development of the tumorigenic epithelial phenotype. The role of stromally derived microenvironmental epigenetic effectors in modulating epithelial growth, hormonal response, morphogenesis and epithelial plasticity is discussed.     

Risk of leukemic transformation in PV and ET patients

Despite a prolonged survival of around 15 years linked to a prolonged complete remission induced by myelosuppression, myeloproliferative syndromes such as polycythemia vera (PV) and essential thrombosis (ET) remain at risk of lethal adverse affects such as thrombotic events and acute transformation. The major risk at diagnosis, in the absence of treatment, is essentially thrombosis. Different therapeutic trials have shown the necessity to maintain circulating blood cells (RBC and platelets counts) near normal levels to avoid thrombosis. Phlebotomies alone in PV lead in the long run to metaplasia and increased platelet counts and should only be kept for emergency cell count reduction. Myelosuppression is thus until recently the most widely accepted effective alternative. However, the effects of long term chronic administration of myelosuppresive agents needs to be analyzed and monitored as the biological changes which appear during the course of these diseases linked or not to the intrinsic clonal haematopoietic abnormality may lead to malignant transformation. Thus, alternative therapies need to be evaluated and predisposition factors taken in account.     

An in vitro study of the antimicrobial activity of some endodontic medicaments and their bases using an agar well diffusion assay

Background:  The aim of this study was to determine the in vitro antimicrobial activities of various endodontic medicaments and their bases against selected organisms using an agar diffusion assay.
Methods:  An agar well diffusion assay was used to test the antimicrobial action of some commonly used endodontic medicaments (Ledermix paste, Pulpdent paste, Ultracal paste, and a 50:50 mix of Ledermix and Pulpdent pastes) and their bases. Three bacterial species ( E. faecalis, P. micros, P. intermedia ) and one yeast ( C. albicans ) were selected. The diameters of growth inhibition zones and pH were assessed.
Results:  P. micros demonstrated the highest level of in vitro resistance. Pulpdent and Ultracal pastes had the highest pH (12.64 and 12.53, respectively). The addition of Pulpdent to Ledermix did not increase the zone sizes significantly.
Conclusions:  All the commercial products showed some in vitro antimicrobial activity. Ledermix paste and the 50:50 Ledermix/Pulpdent mixture being the most effective in this model. The known anti-inflammatory/analgesic properties of Ledermix and the results from this agar model suggest that the 50:50 Ledermix/Pulpdent combination would be the preferred medicament for clinical use in symptomatic cases, even though the addition of calcium hydroxide to Ledermix did not appear to be synergistic in terms of enhancing the antimicrobial action.     

Timing of laparoscopic cholecystectomy in acute cholecystitis

Background Laparoscopic cholecystectomy is associated with an increased conversion rate in acute cholecystitis. Aim To review the operative management of symptomatic cholelithiasis with particular reference to conversion rates and morbidity for laparoscopic cholecystectomy for acute cholecystitis. Methods Patients undergoing cholecystectomy between January 1994 and December 1998 were recruited. Demographic details, diagnosis, duration of symptoms, treatment, outcome, post-operative stay and complications were recorded. Results Complete data were available on 482 patients (84%). Laparoscopic cholecystectomy was attempted in 120 of 132 patients (91%) with acute cholecystitis and 329 of 350 patients (94%) with non-acute gallbladder disease. Conversion rates were 27% (33/120) and 6.7% (22/329) for acute and non-acute gallbladder disease, respectively (p<0.001 x² test). Relating the interval from onset of symptoms to surgery, conversion rates for acute cholecystitis were: <3 days, 5/17 (29%); 4 to 42 days, 14/59 (23%) and >42 days, 14/44 (31%). There were three bile duct injuries, two in the delayed (>45 days) acute group and one in the non-acute group. Conclusion Early laparoscopic cholecystectomy is the treatment of choice for acute cholecystitis, but is associated with a high conversion rate independent of the timing of surgery.     

CCR5△32 mutation does not influence the susceptibility to HCV infection, severity of liver disease and response to therapy in patients with chronic hepatitis C

AIM: To study whether CCR5△32 mutation was associated with viral infection and severity of liver disease.METHODS: Two hundred and fifty two histologically proven, chronic HCV patients (mean age: 41 ± 14 years;M/F: 164/88) were genotyped. PCR based genotyping of 32 bp deletion at the CCR5 locus was done. Fourhundred and eight matched healthy controls were studied to assess susceptibility to HCV infection. To assess correlation of immune gene polymorphism with severity of HCV related liver disease, patients with chronic HCV infection were divided into those with a fibrosis score of ≤ 2 (mild) or ＞ 2 (severe) and histological activity index (HAI) of ≤ 5 or ＞ 5. For correlation between CCR5△32 mutations and response to therapy, 129 patients who completed therapy were evaluated.RESULTS: The majority (89.4%) of the patients were infected with genotype 3. The frequency of homozygous CCR5△32 mutants was comparable to HCV patients as compared to the healthy controls (0.7% vs 0%, P = 0.1).Further more, the frequency of CCR5△32 mutation was comparable in patients with mild or severe liver disease.(P = NS). There was also no association observed with response to therapy and CCR5△32 mutation.CONCLUSION: CCR5△32 mutation does not have a role in disease susceptibility, severity or response to therapy in patients with chronic hepatitis C infection.     

Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression

Prostacyclin (PGI(2)), a potent smooth muscle relaxant, is a major prostaglandin secreted from human myometrium. The concentrations of PGI(2) metabolites in the maternal plasma were reported to be elevated during pregnancy, especially in labor. To clarify the mechanism in PGI(2) secretion from the myometrium, we first investigated the protein expression of cytosolic phospholipase A(2), cyclooxygenase (COX)-1, COX-2, and prostacyclin synthase (PGIS) in the human uterine myometrium at various gestational ages before labor. To elucidate the involvement of labor in the increase in PGI(2) production during labor, we next examined the effect of labor-like cyclic mechanical stretch on PGI(2) production by cultured human myometrial cells. Pregnancy specifically increased COX-1 and PGIS protein expression in the myometrial tissues before labor (P < 0.01 for both). Cyclic mechanical stretch augmented PGIS promoter activity, via activation of activator protein-1 site, and PGIS mRNA and protein expression in cultured human myometrial cells and resulted in a 3.5-fold increase in the concentration of 6-keto-prostaglandin F(1alpha), the stable metabolite of PGI(2), in the culture medium (P < 0.05). However, stretch did not affect the levels of prostaglandin E(2), prostaglandin F(2alpha), or thromboxane A(2) secreted into the same culture media. These results suggest that cyclic mechanical stretch during labor may contribute to the increase in the PGI(2) concentration in the maternal plasma during parturition.     

Factors affecting oral health-related quality of life among pregnant women

Abstract: Objectives: To assess oral health status and to describe the possible factors that could affect the oral health‐related quality of life (OHRQoL) among a group of pregnant rural women in South India. Materials and methods: A total of 259 pregnant women (mean age 26 ± 5.5 years) who participated in the cross‐sectional study were administered the Oral Health Impact Profile (OHIP‐14) questionnaire and were clinically examined for caries and periodontal status. Results: The highest oral impact on quality of life was reported for ‘painful mouth’ (mean: 1.7) and ‘difficulty in eating’ (mean: 1.1). On comparing the mean OHIP‐14 scores against the various self‐reported oral problems, it was seen that the mean OHIP‐14 scores were significantly higher among those who reported various oral problems than those who did not. Those with previous history of pregnancies had more severe levels of gingivitis than those who were pregnant for the first time. Also gingival index scores, community periodontal index of treatment needs scores and previous pregnancies was associated with poorer OHRQoL scores. Conclusion: Increased health promotion interventions and simple educational preventive programmes on oral self‐care and disease prevention during pregnancy can go a long way in improving oral health and lessening its impact on the quality of life in this important population.