Release of naltrexone on buccal mucosa: permeation studies, histological aspects and matrix system design.

Transbuccal drug delivery has got several well-known advantages especially with respect to peroral way. Since a major limitation in buccal drug delivery could be the low permeability of the epithelium, the aptitude of NLX to penetrate the mucosal barrier was assessed. Ex vivo permeation across porcine buccal mucosa 800 microm thick was investigated using Franz type diffusion cells and compared with in vitro data previously obtained by reconstituted human oral epithelium 100 microm thick. Both fluxes (Js) and permeability coefficients (K(p)) are in accordance, using either buffer solution simulating saliva or natural human saliva. Permeation was evaluated also in presence of chemical enhancers or iontophoresis. No significant differences in penetration rate were observed using chemical enhancers; in contrast, Js and K(p) were extensively affected by application of electric fields. Tablets, designed for Naltrexone hydrochloride (NLX) administration on buccal mucosa, were developed and prepared by direct compression of drug loaded (56%) poly-octylcyanocrylate (poly-OCA) matrices. NLX is slowly discharged from buccal tablets following Higuchian kinetic. Histologically, no signs of flogosis ascribable to NLX and/or poly-OCA were observed, while cytoarchitectural changes due to iontophoresis were detected. Buccal tablets containing NLX may represent a potential alternative dosage form in addiction management.     

Bioavailability, biodistribution, and toxicity of BioZn-AAS(1): a new zinc source. comparative studies in rats

Food fortification with a proper zinc compound is an economic and effective strategy to prevent zinc deficiency. BioZn-AAS, a zinc gluconate stabilized with glycine, was compared with zinc sulfate (reference standard), zinc hydroxide, and zinc gluconate, all of them labeled with (65)Zn. This preclinical study was performed on Sprague-Dawley rats of both sexes, and the administered dose was 85 microg/kg of zinc. Bioavailability studies showed that absorption of BioZn-AAS was not statistically different than absorption from other sources in female rats (25.65% +/- 2.20% for BioZn-AAS, 28.24% +/- 4. 60% for ZnSO(4), 24.91% +/- 4.02% for Zn[OH](2), and 25.51% +/- 2. 70% for Zn-gluconate). In the case of the male rats, absorption of BioZn-AAS (27.97% +/- 4.20%) was higher (P<0.05) than that from the other compounds (23.15% +/- 2.90% for ZnSO(4), 22.62% +/- 3.90% for Zn[OH](2), and 22.30% +/- 3.90% for Zn-gluconate). Biodistribution studies demonstrated that the zinc from BioZn-AAS followed the same metabolic pathway as zinc from the other sources. Toxicity studies were performed with 50 female and 50 male rats. The value of oral lethal dose 50 (LD(50)) was 2000 mg/kg for female rats and 1900 mg/kg for male rats. Therefore, we conclude that BioZn-AAS has adequate properties to be considered a proper zinc compound for food fortification or dietary supplementation.     

Performance-based home care for the elderly: the quality of circumstance protocol

The paper introduces a performance-based protocol for use by case managers in home care programs for the elderly. Drawing upon the goal attainment approach to service planning and evaluation, the protocol specifies a set of five observable conditions ranging from the highly desirable to the highly undesirable that correspond to each ADL and IADL dimension plus five other dimensions of importance to community residing frail elders. The conditions documented through the protocol provide a basis for setting explicit expectations of what can be achieved through home care interventions. The paper describes a pilot effort to test the protocol in the Massachusetts state funded home care program. Both the protocol's client assessment form and data collection guide are included as appendices.     

Spontaneous abortion following mid-trimester amniocentesis. Clinical significance of placental perforation and blood-stained amniotic fluid

Summary. The clinical significance of placental perforation and bloodstained amniotic fluid was studied in a group of 7238 Danish women undergoing mid-trimester amniocentesis for prenatal diagnosis under ultrasound guidance. The risk of spontaneous abortion was significantly increased both in pregnancies where the placenta was perforated and in those with blood-stained amniotic fluid. The risk estimate nearly doubled after placental perforation and more than doubled with a bloody tap. It is concluded that for women at relatively low risk of a fetal genetic abnormality, the indication of the amniocentesis should be reconsidered if a placental perforation is unavoidable.     

Function of neutrophilic polymorphonuclear leukocytes in pediatric patients with intrinsic and extrinsic asthma during the intercrisis period

Polymorphonuclear leukocyte function: chemotaxis, NBT and myeloperoxidases activity, was investigated in a group of asthmatic pediatric patients, 26 with intrinsic and 27 with extrinsic asthma, during intercrisis. There was no difference between the extrinsic asthma group and the control one while the group with intrinsic asthma showed an increase of chemotaxis activity (p less than 0.001) and NBT reduction (p less than 0.01); myeloperoxidases activity was similar to the control group. The comparative study of the two types of asthma shows a significant increase of NBT reduction (p less than 0.02) and chemotaxis activity (p less than 0.001) in the intrinsic group. These findings demonstrate that polymorphonuclear function is different in the two main types of asthma during the asymptomatic period.     

Mono, dual and triple moxifloxacin-based therapies for Helicobacter pylori eradication

BACKGROUND: Moxifloxacin is a broad spectrum fluoroquinolone with single daily administration, currently used, above all, for respiratory tract infections. AIM: To compare the efficacy of different 1-week moxifloxacin-based Helicobacter pylori eradication regimens. METHODS: One hundred and twenty H. pylori-positive subjects were randomized to receive moxifloxacin (400 mg/day), moxifloxacin (400 mg/day) and lansoprazole (30 mg/day) or moxifloxacin (400 mg/day), lansoprazole (30 mg/day) and clarithromycin (500 mg b.d.). H. pylori status was reassessed 6 weeks after the end of therapy, and both intention-to-treat and per protocol analyses were performed. RESULTS: One hundred and nineteen of the 120 patients completed the study. H. pylori eradication was achieved in 22.5% of patients treated with moxifloxacin, in 33.3% of subjects treated with moxifloxacin and lansoprazole and in 90% of patients treated with moxifloxacin, clarithromycin and lansoprazole. CONCLUSIONS: Mono and dual moxifloxacin-based therapies are not acceptable for H. pylori eradication; conversely, moxifloxacin-based triple therapy may be considered as a new, effective, first-line therapy option.     

Cost effectiveness of tinzaparin sodium versus unfractionated heparin in the treatment of proximal deep vein thrombosis

OBJECTIVE: To evaluate economic and health implications of tinzaparin sodium, a once a day low-molecular-weight heparin (LMWH), versus unfractionated heparin (UFH) in the treatment of acute deep vein thrombosis (DVT) from a US healthcare payer perspective. STUDY DESIGN: An economic model, composed of two submodules, was created: A short-term module based on clinical trial data covering the first 3 months and a long-term module that projects trial results based on published data for up to 50 years. METHODS: Clinical trial results were combined with data from long-term follow-up studies of DVT in a model that estimates the health and economic consequences of treatment. Both short- and long-term costs with tinzaparin sodium were compared with UFH, as were health outcomes and quality-adjusted life-years (QALYs). RESULTS: Patients treated with tinzaparin sodium are estimated to live a mean of 0.9 years longer on average (0.6 discounted), resulting in an increase of 0.8 QALYs (0.5 discounted). At the same time, lifetime savings are US dollars 621 per patient (1999 values), even when all patients receiving tinzapirin sodium are treated as inpatients. Early discharge of patients receiving tinzaparin sodium, or outpatient treatment, would save between US dollars 3000 and US dollars 5000 per patient. CONCLUSION: Tinzaparin sodium leads to better health outcomes and substantial economic savings compared with UFH treatment when all management costs are considered.