Variation in The Vitamin D Receptor Gene is Associated With Multiple Sclerosis in an Australian Population

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population, one hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age-, sex-, and ethnicity-matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p_Gen = 0.016) and interestingly, a stronger difference for the allelic frequency (p_All = 0.0072). The Apa I alleles were also found to be associated with MS (p_All = 0.04) but genotype frequencies were not significantly different from controls (p_Gen = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D' = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Our results support a role for the VDR gene increasing

Hipervitaminose D em animais

Por meio de revisão da literatura, são apresentados dados referentes ao metabolismo da vitamina D, bem como aos principais aspectos toxicológicos, clínicos, bioquímicos, macroscópicos, microscópicos, ultraestruturais, imuno-histoquímicos e radiográficos de animais intoxicados natural e experimentalmente por essa vitamina, em diferentes espécies. Este estudo objetiva demonstrar a existência de muitas lacunas no conhecimento sobre mineralização fisiológica e patológica, em especial na mediação hormonal do fenômeno, bem como alertar para os riscos de ocorrência dessa intoxicação

Pathogenic mechanism in lung fibrosis. [Synergistic effects of BHT, O/sub 2/, and x rays in mice]

The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O/sub 2/ or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O/sub 2/ or x rays was synergistic. If exposure to O/sub 2/ or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed

Drug metabolizing enzyme systems and their relationship to toxic mechanisms

The metabolism and toxicity of 3-methylfuran (3-MF) are described. The major product of metabolic activation of 3-MF appears to be disemicarbazones. Cursory description of toxic effects of 3-MF on lung and kidneys are provided. 18 refs