New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice

Experimental allergic encephalomyelitis (EAE), the principal animal model of multiple sclerosis, is a genetically determined phenotype. In this study, analyses of the cumulative disease frequencies in parental, F1 hybrid, and F2 mice, derived from the EAE-susceptible SJL/J strain and the EAE-resistant B10.S/DvTe strain, confirmed that susceptibility to EAE is not inherited as a simple Mendelian trait. Whole genome scanning, using 150 informative microsatellite markers and a panel of 291 affected and 390 unaffected F2 progeny, revealed significant linkage of EAE susceptibility to marker loci on chromosomes 7 (eae4) and 17, distal to H2 (eae5). Quantitative trait loci for EAE severity, duration, and onset were identified on chromosomes 11 (eae6, and eae7), 2 (eae8), 9 (eae9), and 3 (eae10). While each locus reported in this study is important in susceptibility or disease course, interactions between marker loci were not statistically significant in models of genetic control. One locus, eae7, colocalizes to the same region of chromosome II as Orch3 and Idd4, susceptibility loci in autoimmune orchitis and insulin-dependent diabetes mellitus, respectively. Importantly, eae5 and eae7 are syntenic with human chromosomes 6p21 and 17q22, respectively, two regions of potential significance recently identified in human multiple sclerosis genome scans.     

Ochratoxin A: a naturally occurring mycotoxin found in human milk samples from Norway

The presence of ochratoxin A (OA) in human milk samples from different regions in Norway was investigated to determine the level of infant exposure to OA from human milk. OA was found in 38 (33%) of 115 human milk samples (range 10-130 ng l(-1)). It was found that 2-26% of the samples contained more than 40 ng l(-1) OA, which will cause a daily intake of OA from human milk exceeding the suggested tolerable dose of 5 ng kg(-1) body weight. Significant regional differences were found.     

Bone transplantation and bone replacement materials

There is a growing need for immediately available material with appropriate qualities for reconstruction of large bone defects. Autologous spongy bone grafts are optimal as to biocompatibility, but are in short supply. Allogenic and xenogenic bone grafts evoke an immunological reaction after implantation and are not biocompatible. In the last thirty years ceramic implants and composites have been developed for bone substitution. New calcium phosphate bone substitutes undergo processes of resorption and precipitation of carbonate apatite that play a part in formation of new bone. These materials are easy to use because of their pastelike consistence. Resorption properties are influenced by particle size, crystallinity and composition. So far, no serious adverse reactions were reported. More clinical experience is necessary especially with composites and combinations with antibiotics, bone growth factors and collagen, to specify the place of these modern calcium phosphates in bone replacement and bone substitution.     

Synthesis and antiplatelet, antiinflammatory, and antiallergic activities of substituted 3-chloro-5,8-dimethoxy-1,4-naphthoquinone and related compounds

2-Amino (6), 2-alkylamino (7-8), 2-methoxy (9), 2-acetamido (10), and 5,8-diacetoxy (11) derivatives of the lead compound 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (4) were synthesized, together with 6,7-dichloro-5,8dimethoxy-1,4-naphthoquinone (5), a positional isomer of 4. Antiplatelet, antiinflammatory, and antiallergic activities were evaluated, and most compounds were quite potent in all assays. Compounds 5 and 9-11 were especially active; however, 5 was ineffective against neutrophil superoxide formation, and 10 was ineffective against mast cell degranulation.     

Evaluation of the injured wrist on the field and in the office

The wrist is a common site of injury in sports, both acute and chronic. Evaluation of wrist injuries requires knowledge of anatomy kinematics, attention to the mechanism of injury, the intensity of training, and a focus on the physical examination for specific injuries.     

The role of hyperglycemia and hyperinsulinemia in the pathogenesis of diabetic angiopathy

The small and large vessel disease associated with diabetes mellitus is responsible for its morbidity and mortality. Although much of the pathogenesis remains to be clarified, the role of hyperinsulinemia and hyperglycemia per se in the progression of vascular disease is beginning to emerge. Hyperinsulinemia increases the release of very low density lipoprotein (VLDL) and may also be responsible for the low HDL cholesterol levels in patients with diabetes. Hyperinsulinemia also contributes to increased blood pressure, which independently promotes vascular disease. High glucose concentrations have direct influence on intracellular signal transduction, including effects on sorbitol pathway and associated changes of pyridine nucleotides, the de novo synthesis of diacylglycerol with subsequent stimulation of protein kinase C, and possibly changes in the cellular generation of myoinositol. Hyperglycemia also exerts long-lasting changes in cellular function, which result from non-enzymatic glycosylation of matrix and membrane proteins with subsequent binding of these proteins to specific receptors. These receptors are termed the advanced glycosylation end-products (AGE) receptors. Their activation leads to an increased release of cytokines and growth factors including PDGF, interleukins, TNF-alpha, and TGF-beta, all of which may act concomitantly in the disease process.     

Changes in dental caries prevalence of school children in Araraquara, SP, Brazil

Previous reports indicate that venous thrombosis is an infrequent problem in patients with HIV infection. Despite this, various HIV-related factors have been proposed as potentially thrombogenic and an HIV-related hypercoagulability has been suggested. At the present time, there exists no consensus of opinion regarding prophylaxis against venous thrombosis for hospitalized patients with HIV. This article aims to provide an overview of venous thrombosis in HIV infection with particular reference to published and personal evidence for possible risk factors and their implications for prophylaxis.     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.