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.     

Synergic effects of nanofiber alignment and electroactivity on myoblast differentiation

The interactions between cells and materials play critical roles in the success of new scaffolds for tissue engineering, since chemical and physical properties of biomaterials regulate cell adhesion, proliferation, migration, and differentiation. We have developed nanofibrous substrates that possess both topographical cues and electroactivity. The nanofiber scaffolds were fabricated through the electrospinning of polycaprolactone (PCL, a biodegradable polymer) and polyaniline (PANi, a conducting polymer) blends. We investigated the ways in which those properties influenced myoblast behaviors. Neither nanofiber alignment nor PANi concentration influenced cell growth and proliferation, but cell morphology changed significantly from multipolar to bipolar with the anisotropy of nanofibers. According to our analyses of myosin heavy chain expression, multinucleate myotube formation, and the expression of differentiation-specific genes (myogenin, troponin T, MHC), the differentiation of myoblasts on PCL/PANi nanofibers was strongly dependent on both nanofiber alignment and PANi concentration. Our results suggest that topographical cues and the electroactivity of nanofibers synergistically stimulate muscle cell differentiation to make PCL/PANi nanofibers a suitable scaffold material for skeletal tissue engineering.     

The effect of epidermal growth factor (EGF) conjugated with low-molecular-weight protamine (LMWP) on wound healing of the skin

This study was designed to develop a skin permeable recombinant low-molecular-weight protamine (LMWP) conjugated epidermal growth factor (EGF) (rLMWP-EGF) by linking a highly positive charged LMWP to the N-terminal of EGF through genetic recombination. We evaluated its biological activity, skin permeability, and wound healing efficacy in?vivo. The cDNA for rLMWP-EGF was prepared by serial polymerase chain reaction for encoding amino acids of LMWP to the vector for EGF. After expression and purification, recombinant EGF site-specifically conjugated with LMWP was obtained. The in?vitro cell proliferation activity was well preserved after LMWP conjugation and was comparable to that of rEGF. rLMWP-EGF showed markedly improved permeability through the three-dimensional artificial human skin constructs, and the cumulative permeation of rLMWP-EGF across the excised mouse skin was about 11 times higher than that of rEGF. Topically applied rLMWP-EGF significantly accelerated the wound closure rate in full thickness as well as a diabetic wound model most probably due to its enhanced skin permeation. These findings demonstrate the therapeutic potential of rLMWP-EGF as a new topical wound healing drug and the site-specific conjugation of LMWP to peptides or proteins by genetic recombination as a useful method for preparing highly effective biomedicines.     

An in vitro study of the antimicrobial activity of some endodontic medicaments against Enteroccus faecalis biofilms

Background: The in vitro antimicrobial activity of a series of endodontic medicaments and their bases against biofilms of Enterococcus faecalis was investigated. Methods: The medicaments tested were Pulpdent paste, Ledermix paste, a 50:50 Ledermix and Pulpdent mixture, and a replica of Ledermix paste. Bases included methyl cellulose with water, polyethylene glycol (PEG), and PEG with zinc oxide, calcium chloride and the other components (inactives) that make up the Ledermix paste base. Biofilms grown on cellulose nitrate membrane filters were exposed to the medicaments for up to 5 days. The number of surviving colony forming units (CFU) was determined at days 1, 3 and 5. The results were expressed as a bacterial survival index (BSI) when compared to the unexposed control. Results: Pulpdent produced the greatest reduction of BSI, followed by the 50:50 mixture of Pulpdent and Ledermix pastes. Ledermix paste, its replica and the individual bases showed no significant reductions in the BSI for E. faecalis. Conclusions: Within the limitations of this laboratory study, calcium hydroxide containing preparations had greater potential for reducing the survival of E. faecalis in a biofilm environment.     

Human Cord Blood Stem Cell Therapy for Treatment of Stress Urinary Incontinence

Our objective in this study was to evaluate the safety and efficacy of transurethral cord blood stem cell injection for treatment of stress urinary incontinence in women. Between July 2005 and July 2006, 39 women underwent transurethral umbilical cord blood stem cell injection performed by one operator at a single hospital. All patients had stress urinary incontinence. The patients were evaluated 1, 3, and 12 months postoperatively. No postoperative complications were observed. 28 patients (77.8%) were more than 50% satisfied according to the Patient''s Satisfaction results after 1 month, 29 patients (83%) were more than 50% satisfied according to the Patient''s Satisfaction results after 3 months, and 26 (72.2%) continuously showed more than 50% improvement after 12 months. Intrinsic sphincter deficiency and mixed stress incontinency improved in the ten patients evaluated by urodynamic study. Our results suggest that transurethral umbilical cord blood stem cell injection is an effective treatment for women with all types of stress urinary incontinence.