Antibodies to Ro/La, Cenp-B, and snRNPs Antigens in Autoimmune Hepatitis of North America versus Asia: Patterns of Immunofluorescence, ELISA Reactivities, and HLA Association

To assess whether demography is one of theimportant factors determining antibody response tonuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La,snRNPs (A, 70K, B/B), and Cenp-B], weinvestigated 95 and 47 sera of autoimmune hepatitis (AIH) fromNorth America and Asia, respectively, byimmunofluorescent (IF) and recombinant ELISA.Correlations among nuclear IF patterns, ELISA, anddisease indices were analyzed. The frequency and titer of individualantibodies differed significantly between the groups.Patients with speckled patterns were younger in bothregions and had higher aspartate aminotransferase levels only in North America. HLA-A1, B8, DQ2,and DR4 or DR3 or both in North America, and A2, B61,DQ7, and DR4 in Asia were predominant. In Asia, B61correlated with anti-70K, and DQ7 correlated with antibodies to 52K, Cenp-B, and B/B. InNorth America, A1, B8, DR3 haplotype, and DQ2 correlatedwith antibodies to A and 70K. Anti-B/B and DR4 inNorth America, and A2 in Asia, were associated withconcurrent immunologic disorder. Individual ANA clusterscorrelated with individual HLA in the demography, anddifferent HLA alleles might determine disease expressionas well as different ANA being produced inAIH.     

The dental implications of chronic use of acidic medicines in medically compromised children

Objective: Liquid oral medicines form a significant proportion (11%) of the medicines used by the population as a whole, either prescribed or over the counter. The active agent, as well as some of the other ingredients, can pose a threat to oral health. Method: Eight liquid oral medicines and two effervescent preparations routinely prescribed for longterm use by paediatric renal patients were assessed for titratable acidity and pH values. Results: All of the medicines tested were acidic and the majority were well below the critical pH of 5.5 at which enamel demineralisation takes place. The titratable acidity values, at a pH of 6.7, ranged between 0.01 and 1.54 for the liquid preparations but were 8.4 and 10.6 for the two effervescent tablets tested. Conclusion: Surplus acid in effervescent preparations while ensuring palatability of medicines and thus compliance, may produce unwanted dental side effects in children who are already medically compromised.     

Cytotoxic activity of moronic acid and identification of the new triterpene 3,4-seco-olean-18-ene-3,28-dioic acid from Phoradendron reichenbachianum

The cytotoxic compound moronic acid (1) and the new tetracyclic triterpene 3,4-seco-olean-18-ene-3,28-dioic acid (2), were isolated from the aerial parts of the medicinal plant Phoradendron reichenbachianum (mistletoe, Loranthaceae) through a bioassay-guided fractionation. In addition, squalene, glycerol trilinoleate, morolic acid, betulonaldehyde, betulinaldehyde, alpha-germanicol, lupeol, beta-sitosterol and beta-sitosteril glucopyranoside, were identified in this plant species. The structures were elucidated on the basis of chemical and spectroscopic evidence.     

Observation of spontaneous cerebrospinal fluid rhinorrhoea to body mass index: a preliminary report

The purpose of this retrospective study is to determine whether there is a correlation among overweight, gender and the risk of development of spontaneous cerebrospinal fluid (CSF) rhinorrhoea. The clinical data of eight patients diagnosed with spontaneous cerebrospinal fluid rhinorrhoea who had been treated at our tertiary referral centre between 1998 and 2007 were assessed. Demographically, seven patients were female and one male with ages ranging from 14 to 53 years with a mean age of 43.6 years. This observation revealed that all patients were overweight with a mean body mass index (BMI) of 32.5 kg/m2. This study suggests that there is a trend of increasing BMI to the risk of developing a spontaneous CSF rhinorrhoea.     

Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of human lymphoblastoid cells or in utero exposure of CD-1 mice to single agents or drug combinations

Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using cell cloning assays for assessing the effects of individual drugs/drug combinations in (1) TK6 human lymphoblastoid cells exposed in vitro and (2) splenic lymphocytes from male CD-1 mice exposed transplacentally on days 12-18 of gestation. In TK6 cells, dose-related increases in HPRT and TK mutant frequencies were found following 3 days of exposure to AZT or 3TC alone (33, 100, or 300 microM), or to equimolar amounts of AZT-3TC. Compared with single drug exposures, AZT-3TC coexposures generally yielded enhanced elevations in HPRT and TK mutant frequencies. Mutagenicity experiments with ABC alone, or in combination with AZT-3TC, were complicated by the extreme cytotoxicity of ABC. Exposure of cells either to relatively high levels of AZT-3TC short-term (100 microM, 3 days), or to peak plasma-equivalent levels of AZT-3TC for an extended period (10 microM, 30 days), resulted in similar drug-induced mutagenic responses. Among sets of mice necropsied on days 13, 15, or 21 postpartum, Hprt mutant frequencies in T-cells were significantly elevated in the AZT-only (200 mg/kg bw/day) and AZT-3TC (200 mg AZT + 100 mg 3TC/kg bw/day) groups at 13 days of age. These results suggest that the mutagenicity by these nucleoside analogs is driven by cumulative dose, and raises the question of whether AZT-3TC has greater mutagenic effects than AZT alone in perinatally exposed children.     

New 2-Thiopyridines as Potential Candidates for Killing both Actively Growing and Dormant Mycobacterium tuberculosis Cells

From in vivo observations, a majority of M. tuberculosis cells in latently infected individuals are in a dormant and probably nonculturable state, display little metabolic activity, and are phenotypically resistant to antibiotics. Despite many attempts, no specific antimicrobials effective against latent tuberculosis have yet been found, partly because of a lack of reliable and adequate in vitro models for screening of drug candidates. We propose here a novel in vitro model of M. tuberculosis dormancy that meets the important criteria of latency, namely, nonculturability of cells, considerable reduction of metabolic activity, and significant phenotypic resistance to the first-line antibiotics rifampin and isoniazid. Using this model, we found a new group of 2-thiopyridine derivatives that had potent antibacterial activity against both actively growing and dormant M. tuberculosis cells. By means of the model of M. tuberculosis nonculturability, several new 2-thiopyridine derivatives were found to have potent antitubercular activity. The compounds are effective against both active and dormant M. tuberculosis cells. The bactericidal effects of compounds against dormant M. tuberculosis was confirmed by using three different in vitro models of tuberculosis dormancy. The model of nonculturability could be used as a reliable tool for screening drug candidates, and 2-thiopyridine derivatives may be regarded as prominent compounds for further development of new drugs for curing latent M. tuberculosis infection.     

Reduction of autogenous bone graft resorption by means of bio-oss coverage: a prospective study

Bone grafting may be required prior to implant placement, at the time of implant placement, or subsequent to it. The aim of this study was to compare the healing of onlay block grafts when deproteinized bovine bone coverage was used with the healing of the grafts without such coverage. The purpose was a clinical evaluation of deproteinized bovine bone's ability to reduce grafted bone resorption. The results indicated that bovine bone can be placed over grafted areas, taking advantage of its osteoconductive properties and compensating for the natural bone resorption caused by remodeling.