Rupatadine effectively prevents the histamine-induced up regulation of histamine H1R and bradykinin B2R receptor gene expression in the rat paw.

BACKGROUND: Activation of histamine H1 receptor (H1R) is a well-known hallmark of allergic and inflammatory pathology. Both types of bradykinin receptors (B1R and B2R) are also known to contribute significantly to the latter and some sort of functional interaction between them and H1R has been alluded to in the past. Here we use an experimental model of rat paw oedema formation to examine the effect of exogenously added histamine on the gene expression of H1R and bradykinin receptors B1R and B2R, alone or in combination to rupatadine, a second generation antihistamine agent. METHODS: Histamine-induced oedema formation was monitored with a plethysmometer. The gene expression of H1R, B1R and B2R was analyzed with both conventional and real-time PCR. Rupatadine fumarate was used in pure form and administered intraperitoneally, prior to histamine injection into the paw. Microscopy of haematoxylin and eosin-stained sections of paw tissue was used to examine effects on tissue architecture. RESULTS: Histamine injection into the paw resulted in significant up regulation of H1R and B2R without inducing significant cellular infiltration, but appears to affect less the expression of B1R. Rupatadine was, under the conditions used in this study, very effective in preventing this effect and in suppressing oedema formation through its antihistamine action. CONCLUSION: Rupatadine has a suppressing effect on H1R and B2R gene expression which could add to its efficacy towards allergy and allergy-like conditions.

Methylenetetrahydrofolate reductase C677T polymorphism: association with risk for childhood acute lymphoblastic leukemia and response during the initial phase of chemotherapy in greek patients.

BACKGROUND: As of late, a number of studies have focused on the association of the gene for methyletetrahydrofolate reductase (MTHFR) with risk for acute lymphoblastic leukemia (ALL) in children and in adults, as well as with response to chemotherapy. The degree of this association may vary according to the ethnic background and geographic localization of the population under study, or the phase of treatment when response to chemotherapy is concerned. PROCEDURE: We have analyzed the MTHFR C677T polymorphism in 52 patients and 88 control individuals, all ethnic Greek residents of northern Greece, and examined the association of this polymorphism with (a) susceptibility to childhood ALL and (b) the distribution of average plasma alanine aminotransferase (ALT) levels, white blood cell counts (WBC), and hemoglobin levels (Hb) during the induction and consolidation phases of treatment. RESULTS AND CONCLUSIONS: We were able to detect a statistically significant protective effect, with respect to ALL, associated with carriage of the MTHFR 677T allele [OR = 0.387 (95% CI = 0.193-0.776)]. In addition, we observed a general tendency towards lower values in all three parameters studied, associated with the MTHFR 677CC genotype, which was more evident in the transition from the induction to the consolidation phase, indicating that MTHFR genotyping may be of prognostic value in the early phase of treatment for childhood ALL, in our population.

An association study of a functional catalase gene polymorphism, -262C-->T, and patients with Alzheimer's disease.

According to the oxidative stress hypothesis which has been proposed as one of a number of possible mechanisms underlying pathogenesis of Alzheimer's disease (AD), accumulation of hydrogen peroxide in the brain of affected individuals, due to overproduction and/or insufficient detoxification, can trigger a cascade of neurotoxic events, thus contributing to the neuronal damage characteristic of the disease. The upregulation of enzymes that are able to neutralize hydrogen peroxide (catalase, peroxidases) would then be conceivably able to offer at least some protection from the damaging effects of this agent. In this study we examined the distribution of a functional polymorphism in the gene for catalase, -262C-->T, in an independent population of 137 AD patients and 130 control individuals. The presence of the polymorphism, which results in the elimination of a SmaI restriction site, was tested with a PCR amplification/SmaI digestion-based assay. No significant difference has emerged from the comparison of either genotype or allele frequencies (P>0.5). We conclude that the catalase gene -262C-->T polymorphism does not confer a protective effect with respect to AD.

Interleukin-1A polymorphism is not associated with late onset Alzheimer's disease.

Over the past few years, association studies have proposed a number of potential genetic risk factors for Alzheimer's disease (AD). With the exception of the varepsilon4 allele of the apolipoprotein E gene, whose association with the late onset type of AD (LOAD) has been confirmed, the relative significance of most of these associations is still in question. A polymorphism in the interleukin-1A gene (IL-1A2) has been suggested as a risk factor for the early onset as well as for LOAD. In this study, the distribution of IL-1A alleles was examined in a cohort of predominantly LOAD patients and in control individuals. No significant difference was detected in genotype or allele frequencies (odds ratios of 0.929 and 0.743, respectively; P>0.5). We conclude that IL-1A genotype is not a major risk factor for LOAD.

No association between the lipoprotein lipase S447X polymorphism and Alzheimer's disease.

Results from various genetic association studies of the lipoprotein lipase (LPL) S447X polymorphism and Alzheimer's disease (AD), range from a statistically significant negative association of clinically examined patients to a non-significant but consistent trend for under-representation of the X447 allele in neuropathologically confirmed subjects. In this report we have compared the distribution of the above polymorphism in an independent group of clinically diagnosed AD patients, including a subgroup where the disease was pathologically confirmed, and a spousal control group. No statistically significant differences emerged from this comparison. We conclude that LPL cannot be a major factor in pathogenesis of AD.