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.     

Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors

OBJECTIVE: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). DESIGN: CD4 cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. METHODS: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. RESULTS: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50% effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. CONCLUSION: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function.     

Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine

In the present prospective, census-based study we have investigated the prevalence of organ-specific and non-organ-specific autoantibodies (AAb) in 152 unselected Cameroonians aged 60 years and older living in the community. AAb were detected in 49% of the participants. Non-organ-specific AAb (47%) predominated over organ-specific AAb (7%). Anti-TPO, anti-Tm, anti-Tg and anti-PC AAb were completely absent. RF was the most frequent AAb, being found in 57 (38%) cases. The prevalences of anti-SMA and RF were significantly higher in women than in men (respectively, P=0.023 and P=0.016). Higher serum concentrations of gammaglobulins were accompanied by a higher prevalence of RF (P < 0.0001) and a lower prevalence of ANA (P=0.036). The overall prevalence of AAb was higher in the filaria-infected (60%) compared to the non-infected (42%) participants (P=0.046). There was no significant influence of the vitamin D status, number of pregnancies, physical activity or medication use on the prevalence of AAb. In this study a heterogeneous pattern for the presence of the various AAb was found. Some AAb, which are commonly encountered in other studies on elderly subjects, were completely absent in this population. This diversified pattern of AAb prevalence therefore argues in favour of exogenous influences in the occurrence of AAb in elderly populations.     

Neuropathological Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD) and Other Human Spongiform Encephalopathies (Prion Diseases)

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD - sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immuno-reactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spon-giosis. This includes status spongiosus (“spongiform state”), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of “burnt-out” CJD), “spongy” changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.     

Herion addicts infected by HBV and HIV have a low prevalence of HBV DNA in peripheral blood mononuclear cells

Several reports show that the prevalence of HBV (hepatitis B virus) carriers in HIV (human immunodeficiency virus) infected populations is significantly higher than in HIV seronegative individuals, independent of the risk group for HIV, that is, homosexuals or drug abusers. In this context, evaluation of the simultaneous presence of HBV and HIV in PBMCs (peripheral blood monuclear cells) is of particular interest for at least 2 reasons: 1) the possible reciprocal influence of the 2 viruses when they infect the same cell; 2) the possibility that HIV-iduced hematological disorders could indirectly influence the settling of HBV in blood cell populations. We report data on the frequency of PCR positivity for HBV DNA in PBMCs from 62 HIV infected patients, rigorously selected by risk group, that is, intravenous use of heroin for at least 3 years and syringe promiscuity. Sixtyseven HIV negative individuals who never used any drug formed the control group. The analysis of the cases positive for HBV DNA in PBMCs showed that 1) the overall prevalence of PCR positivity found in HIV infected patients was significantly lower than that registered in the control group; 2) PCR positivity among the subjects who were HBsAg negative and anti-HBV positive was extremely low in the HIV infected patients (3.7%) but quite frequent in the HIV negative subjects (37.0%). The results support the hypothesis that, unlike the HIV negative individuals, our HIV infected patients exhibited HBV DNA in PBMCS almost exclusively when they presented with active HBV replication.     

Viral load,CD4 percentage,and delayed-type hypersensitivity in subjects receiving the HIY-1 Immunogen and antiviral drug therapy

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.