Elimination of microfilaria in dogs infected with zoonotic Dirofilaria repens would be desirable to reduce further spread. Moxidectin has demonstrated efficacy against microfilariae and safety in dogs infected with Dirofilaria immitis and could be an option for controlling D. repens microfilariae. A field study with 64 dogs previously confirmed positive for D. repens microfilaria was conducted in Hungary, in which a spot-on product (Advocate, Bayer) was tested. Treatments were applied to 44 dogs once a month for 3 months (five dogs) or 6 months (22 dogs), alternatively every 2 weeks for 6 months (17 dogs). Twenty dogs remained untreated. Microfilaria counts were performed once a month and for a further 6 months following the last treatment. Two weeks after the first treatment, 38 of 44 dogs were microfilaria negative. Four weeks after the initial treatment, one dog still showed a low microfilaria count. Following the second treatment, all treated dogs were negative. This status was maintained during the 6-month observation period after the last treatment. These data demonstrate the successful long-lasting elimination of microfilariae. Moreover, it may be supposed that adult D. repens were killed based on the observation that no further microfilariae were seen up to 6 months after the end of the treatment period.
Abstract-The authors tested 123 genotypes described in 54 papers published in the journal Neurology between 1999 and 2002 to ascertain whether these genotype distributions deviated from Hardy-Weinberg equilibrium (HWE). Unreported deviations from HWE in 19 genotype distributions described in 11 of the papers were discovered. The authors also report additional information that could have been extracted after calculating HWE and conclude that HWE values should be mandatory in population genetic studies published in Neurology. NEUROLOGY 2004;63:357-358 The gene frequencies at a locus in a randomly interbreeding diploid population and population genotype frequencies remain constant from generation to generation if mating is random and if mutation, selection, and migration do not occur. A mathematical formula created by Hardy and Weinberg 1-4 allows for this equilibrium to be tested in studied populations.The Hardy-Weinberg law is suitable for testing the hypothesis of panmixia (random mating within a breeding population) and evolutionary stasis. It is a null hypothesis in genetic studies for testing the suitability of the enrolled reference population and for detecting even weak associations between genotype and disease. However, Hardy-Weinberg equilibrium (HWE) is not always calculated and published in papers investigating population genetics, as we found after reviewing a sample of papers published in recent volumes of Neurology.Subjects and methods. We reanalyzed genotypes described in papers published in Neurology between 1999 and 2002. Enrollment criteria were investigation of biallelic genetic polymorphisms with Mendelian inheritance and case-control study design. We calculated HWE values for each published genotype in each subject group using the Arlequin program (http://anthropologie. unige.ch/arlequin/). 6,7 The level of significance was set at p Ͻ 0.05.
5-fluorouracil (5-FU) is widely used in the treatment of gastric and colorectal cancer. Recent microrarray studies associated different gene lists with 5-FU resistance. A major challenge in the genomic era is to find the most validated genes, and to decipher the regulatory networks responsible for the expression changes in a set of co-regulated transcripts. Our aim was to find genes repeatedly associated with 5-FU resistance, and to identify transcription factors (TFs) having overrepresented binding sites (TFBSs) in the promoter regions of genes associated with 5-FU resistance. Materials and Methods: The analyzed data originated from 5 different publications describing genome-wide gene expression patterns associated with 5- FU resistance in gastric and colorectal cancer. First, a data warehouse containing all genes associated with resistance was set up. 39 genes were identified which were repeatedly associated with resistance. Of these, using the EZ-Retrieve web service, proximal promoter sequences were available for 33 genes. The MotifScanner software was used to detect TFBSs in this set of sequences. Results: A total of 200 different TFBSs were identified. Using the statistics tool of the Java program TOUCAN, 4 binding sites were found to be significantly overrepresented: NFKappaB50 (p = 0.01), EGR2 (p = 0.027), EGR3 (p = 0.007), and NGFIC (or EGR4) (p = 0.001). These genes intercept apoptotic pathways at multiple locations in the tumor cells. Conclusion: We identified a consensus gene list associated with 5-FU resistance, performed an in silico comparative promoter analysis, and highlighted the potential implication of some TFs in the development of chemoresistance.
Background: Some patients with inflammatory bowel disease (IBD) do not respond to infliximab (IFX) therapy. Gene expression studies revealed genes that may help to predict non-responding IBD patients. Our purpose was to validate the discriminating power of published genes. Methods:Microarray datasets of IBD patients responding or non-responding to IFX were downloaded from GEO database ('transcriptomic arm'). Published genes discriminating responding and non-responding patients were identified in PubMed ('biomarker arm'). Using ROC-analysis, the discriminating performance of genes in 'biomarker arm' were re-tested in each datasets of 'transcriptomic arm'. We also performed an independent analysis of colon biopsy datasets to identify novel discriminating genes. Results:The transcriptomic arm of four GEO datasets (3 and 1 from colon biopsies and blood cells, respectively) included 99 patients (of those, 59 and 40 were IFX responder and non-responder, respectively). Of the 65 candidate genes reported in biopsy specimens 25 genes discriminated significantly (p<0.05) infliximab responders and nonresponders in the three biopsy datasets consistently. Of the 39 candidate genes reported in peripheral blood 9 genes provided significant discrimination after re-testing. Independent analysis of three biopsy datasets identified the top five genes. Three genes (IL13RA2, PTGS2 and WNT5A) were highly effective discriminator in each analysis. Conclusion:This analysis identified IL13RA2, PTGS2 and WNT5A, three genes in colonic tissues of IBD patients as suitable to discrimination between patients responding and non-responding to IFX therapy. These genes encode proteins implicated in intestinal pathology; the high expression in non-responding patients may indicate important targets in IBD therapy.
Tourniquet application proved to be capable of inducing absolute lower limb ischemia, in contrast to infrarenal aortic ligation, where a rich collateral system is considered to help mitigate the injury.
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