Multifunctional microcapsules for pancreatic islet cell entrapment: design,preparation and in vitro characterization

Great advances in cell transplantation have been made, including the recent, remarkable success in pancreatic islet transplantation for the treatment of type 1 diabetes mellitus. Unfortunately, the transplanted cells are very susceptible to oxidative stress that cause severe damage to either allo- or xenogeneic islets upon graft in diabetic patients. Consequently, the transplanted islet functional life span is significantly shortened. The aim of this study was to examine the possible effects of antioxidants on in vitro cultured adult rat islets, and to evaluate the effects of a prolonged-release formulation, in form of cellulose acetate (CA) microspheres, on Vitamin D(3) activity. Isolated rat islets, both free and entrapped in microspheres were treated with Vitamin D(3). The effects of the vitamin were studied at 3, 6 and 9 days of in vitro cell culture. According to insulin secretory patterns, treatment with Vitamin D(3) of both free and CA entrapped microspheres, increased the insulin output as compared to untreated controls. Such positive effects were confirmed under islet static incubation with glucose at day 6. These results suggest that pancreatic islets can be advantageously treated with anti-oxidising vitamins before implantation, and speculatively, with the help of special delivery systems, throughout the islet cell life span, in the post-transplant time period.     

The Facioscapulohumeral muscular dystrophy region on 4qter and the homologous locus on 10qter evolved independently under different evolutionary pressure

Background  

The homologous 4q and 10q subtelomeric regions include two distinctive polymorphic arrays of 3.3 kb repeats, named D4Z4. An additional BlnI restriction site on the 10q-type sequence allows to distinguish the chromosomal origin of the repeats. Reduction in the number of D4Z4 repeats below a threshold of 10 at the 4q locus is tightly linked to Facioscapulohumeral Muscular Dystrophy (FSHD), while similar contractions at 10q locus, are not pathogenic. Sequence variations due to the presence of BlnI-sensitive repeats (10q-type) on chromosome 4 or viceversa of BlnI-resistant repeats (4q-type) on chromosome 10 are observed in both alleles.     

Chromosome abnormalities in breast fibroadenomas

A cytogenetic study on 25 breast fibroadenomas from 17 women is reported. Seven tumors in five patients showed clonal structural chromosome changes. In three patients the breaks involved chromosome 12, occurring in two tumors in band 12p12 and in band 12q15 in all three tumors of one patient. The finding of an identical aberration, t(11;12)(q21;q15), in three adenomas from the same patient strongly suggests a clonal origin of multiple fibroadenomas of the breast.     

Helicobacter pylori infection affects eosinophilic cationic protein in the gastric juice of patients with idiopathic chronic urticaria

BACKGROUND: Helicobacter pylori, the main cause of gastritis and peptic ulcer, has been associated with idiopathic chronic urticaria (ICU), an immunological skin disorder of unknown origin. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils involved in the pathogenesis of ICU. We assessed serum/gastric juice ECP levels and gastric mucosal eosinophil infiltration in ICU patients infected or not with H. pylori and evaluated the modification after bacterium eradication. METHODS: 33 patients with ICU and 25 dyspeptic controls underwent upper gastrointestinal endoscopy for histological evaluation and assessment of H. pylori infection. One-week triple therapy was given to H. pylori-positive patients. Serum and gastric juice ECP levels, eosinophil infiltration from gastric mucosal sections and urticaria symptoms were evaluated in all patients at enrollment and 8 weeks after eradication. RESULTS: 19 of 33 (57%) ICU patients and 16 of 25 (64%) controls were found to be infected with H. pylori. Serum ECP was significantly higher in ICU patients compared to controls, regardless of infectious status. Gastric juice ECP and gastric eosinophil infiltration were significantly higher in infected ICU patients when compared both to uninfected ICU patients and controls. H. pylori eradication determined a significant decrease in gastric juice ECP and gastric eosinophil infiltration only in ICU patients. Moreover, a total or partial remission of urticaria symptoms was observed only in ICU patients in whom the bacterium was eradicated. CONCLUSIONS: Although H. pylori infection affects gastric juice ECP and eosinophil infiltration of ICU patients, the role of the bacterium in the pathogenesis of this skin disorder still remains uncertain.     

Incidence and determinants of bacterial infections in HIV-positive patients receiving anti-Pneumocystis carinii/Toxoplasma gondii primary prophylaxis within a randomized clinical trial

We assessed the incidence and determinants of bacteremia, pneumonia, and sinusitis/otitis in HIV-positive people receiving cotrimoxazole (CTX) or dapsone-pyrimethamine (DP) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) within a randomized clinical trial. In total, 244 patients were randomized: 122 were assigned to CTX and 122 to DP. In the cohort, 22 bacteremia, 63 pneumonia, and 39 sinusitis/otitis cases were observed. Incidence rates of bacteremia, pneumonia, and sinusitis/otitis as well as the 2-year probability of remaining free from any bacterial infection were not significantly different between the two groups. At multivariate analysis, the risks of developing bacteremia and pneumonia were found to be independently increased by the use of a central venous catheter (hazard ratio [HR], 4.48; p <.05 and HR, 4.13; p <.01, respectively) and by hospitalization (HR, 28.82; p <.05 and HR, 10.15; p <.05, respectively). In conclusion, CTX at the dosage employed for primary PCP/TE prophylaxis does not seem to protect against bacterial infections more than second-line DP.     

Long-term ethanol administration enhances age-dependent modulation of redox state in brain and peripheral organs of rat: protection by acetyl carnitine

Evidence is accumulating that intermediates of oxygen reduction may be associated with the development of alcoholic disease. Free radical-induced perturbation of the oxidant/antioxidant balance in the cell is widely recognized as the main causative factor of age-related disorders. In the present study we investigated the effects of 20 months of ethanol consumption on the antioxidant defense system in different rat organs compared with normal aging in the absence and presence of treatment with L-acetyl carnitine. We demonstrate that aged rats underwent significant perturbation of the antioxidant defense system, as indicated by depletion of reduced glutathione (GSH) content, increased oxidized GSH, free radical-induced luminescence associated with increased hydroxynonenal content and decreased GSH reductase activity. These modifications, observed particularly in brain and liver compared with other organs, were enhanced by long-term alcohol exposure and, interestingly, were significantly reduced with acetyl carnitine supplements. Our results indicate that decreased GSH reductase activity and thiol depletion are important factors in effecting a pathogenic role for oxidative stress in aging and in all situations in which age-correlated and oxidant-induced changes occur, such as in alcoholism. Administration of acetyl carnitine greatly reduces these metabolic abnormalities. Our findings support its pharmacological potential in the management of alcoholic disturbances.     

Immunology: Mitogen-induced lymphocyte proliferation and peripheral blood mononuclear cell {beta}-endorphin concentrations in primary dysmenorrhoea

Dysmenorrhoea is a recurrent painful disease which causes physicaland psychological stress. The purpose of the present study wasto investigate whether there was a measurable derangement ofimmune cells and immune responses in women with severe primarydysmenorrhoea. On day 26 of one cycle and on days 1 and 3 ofthe following cycle we measured polyclonal, mitogen-inducedlymphocyte proliferation and -endorphin concentration in peripheralblood mononuclear cells obtained from 16 infertile women withnormal pelvis, of whom eight had and eight did not have thedisorder. In women with dysmenorrhoea, polyclonal mitogen-inducedlymphocyte proliferation was lower than in controls on all 3days considered, but the difference was statistically significantonly on day 26 (43 605 ± 9876 µg/ml versus 67 305± 15 249 µg/ml; P < 0.01). Monocyte -endorphinconcentrations in the patients with dysmenorrhoea were significantlyelevated on day 3 compared to controls (67.8 ± 24.3 pg/10⁶cells versus 29.7 ± 6.9 pg/10⁶ cells; P < 0.05). Ourresults demonstrate that immune responses are modified in patientswith primary dysmenorrhoea. These effects are independent ofcirculating hormone concentrations and are consistent with therole of dysmenorrhoea as a stressful event.     

Two-center collaborative evaluation of the performance of the BD Phoenix automated microbiology system for identification and antimicrobial susceptibility testing of Enterococcus spp. and Staphylococcus spp

The performance of the BD Phoenix Automated Microbiology System (BD Diagnostic Systems, Sparks, Md.) was assessed for identification (ID) and antimicrobial susceptibility testing (AST) for the majority of clinically encountered bacterial isolates in a European collaborative two-center trial. A total of 469 bacterial isolates of the genera Staphylococcus (275 isolates), Enterococcus (179 isolates), and Streptococcus (15 isolates, for ID only) were investigated; of these, 367 were single patient isolates, and 102 were challenge strains tested at one center. Sixty-four antimicrobial drugs were tested, including the following drug classes: aminoglycosides, beta-lactam antibiotics, beta-lactam-beta-lactamase inhibitors, carbapenems, cephems, folate antagonists, quinolones, glycopeptides, macrolides-lincosamides-streptogramin B (MLS), and others. Phoenix ID results were compared to those of the laboratories' routine ID systems (API 32 Staph, API 32 Strep, and VITEK 2 [bioMérieux, Marcy l'Etoile, France]); Phoenix AST results were compared to those of frozen standard broth microdilution (SBM) panels according to NCCLS guidelines (NCCLS document M 100-S 9, approved standard M 7-A 4). Discrepant results were repeated in duplicate. Concordant IDs of 97.1, 98.9, and 100% were observed for staphylococci, enterococci, and streptococci, respectively. For AST results the overall essential agreement was 93.3%; the category agreement was 97.3%; and the very major error rate, major error rate, and minor error rate were 1.2, 1.9, and 1.3%, respectively. In conclusion, the Phoenix ID results showed high agreement with results of the systems to which they were being compared; the AST performance was highly equivalent to that of the SBM reference method.