Whole genome analysis of the action of interferon-beta.

OBJECTIVES: To characterize the IFNbeta1a-regulated gene expression on leukocytes of Multiple Sclerosis (MS) patients using microarrays with whole human genome representation. METHODS: Genes differentially expressed by interferon-beta were identified by a microarray in vitro study performed in leukocytes obtained from 5 MS relapsing-remitting patients. RESULTS: Following the culture of peripheral blood mononuclear cells from MS relapsing-remitting patients for 24 hs with IFNbeta1a, the expression of 868 genes was modified: 545 increased (including CXCL11, CCL8, INDO, IFI27, CFB, CXCL10 and IFIT1) and 323 diminished (including RBP7, SEPT5, RNF8, ADORA2B and FOS). CONCLUSIONS: Since many of them were previously recognized as involved in MS pathogenesis, the IFNbeta1a mechanism of action could imply a compensatory regulation of systems deregulated in MS.

Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis.

OBJECTIVES: Recombinant human interferon-beta (IFN-b) is a well-established treatment for multiple sclerosis (MS). The regulatory process for marketing authorization of biosimilars is currently under debate in certain countries. In the EU, EMEA has clearly defined the process including overarching and product-specific guidelines, which includes clinical testing. Biosimilarity needs to be based on comparability criteria, including at least molecular characterization, biological activity relevant for the therapeutic effect and relative bioavailability ("bioequivalence"). In the case of such complex diseases as MS, where the effect of treatment is not so directly measurable, in vitro tools can provide additional data to support comparability. Genomic microarrays assays might be useful to compare multisource biopharmaceuticals. The aim of the present study was to compare the pharmacodynamic genomic effects (in terms of transcriptional regulation) of two recombinant human IFN-I(2)1a preparations on lymphocytes of multiple sclerosis patients using a whole genome microarray assay. METHODS: We performed an ex vivo whole genome expression profiling of the effect of two preparations of IFN-I(2)1a on non-adherent mononuclears from five relapsing-remitting MS patients analyzing microarrays (CodeLink Human Whole Genome). Patients blood was drawn, PBMCs isolated and cultured in three different conditions: culture medium (control), 1,000 U/ml of IFN-I(2)1a (BLA- (STOFERON, Bio Sidus) and 1,000 U/ml of IFN-I(2)1a (REBIF, Serono) RNA was purified from non-adherent cells (mostly lymphocytes), amplified and hybridized. Raw data were generated by CodeLink proprietary software. Data normalization, quality control and analysis of differential gene expression between treatments were done using linear model for microarray data. Functional annotation analysis of IFN-I(2)1a MS treatment transcription was done using DAVID. RESULTS: Out of the approximately 45,000 human sequences examined, no evidence of differential regulation was found when both treatments were compared (minimum adjusted p-value > 0.999). The IFN-I(2)1a effect differentially regulated the expression of 868 genes. The expression of standard markers such as GTP cyclohidrolase, MxA, and OAS isoenzymes A and B changed as a consequence of the action of IFN-I(2)1a. CONCLUSIONS: This exhaustive and highly sensitive assay did not show differences in the genomic expression profile of these two products under the assayed experimental conditions. These results suggest that this technology might be useful for the initial comparison of biosimilars, being part of a comprehensive comparability program that includes clinical testing.

Improvement of the immune response to foot and mouth disease virus vaccine in calves by using Avridine as adjuvant.

The epidemiological analysis of the cattle population during the eradication plan of foot and mouth disease (FMD) in Argentina clearly indicated a higher incidence of the disease in animals within their first year of age. It is important to improve the efficacy of the vaccination in those animals. In a previous report, we have shown the effect of an immunomodulator, Avridine (Avr), in the enhancement of the immune response elicited by FMD virus (FMDV) vaccines in experimental hosts [Berinstein, A., Pérez Filgueira, M., Schudel, A., Zamorano, P., Borca, M., Sadir, A.M., 1993. Avridine and LPS from Brucella ovis: effect on the memory induced by foot-and-mouth disease virus vaccination in mice. Vaccine 11, 1295-1301]. In this report, we analyze the effect of Avr in the improvement of the anti-FMDV immune response elicited in young animals immunized with a tetravalent vaccine. The anti-FMDV antibody response was evaluated using a liquid-phase blocking sandwich ELISA (LPBE) [Smitsaart, E.N., Zanelli, M., Rivera, I., Fondevila, N., Compaired, D., Maradei, E., Bianchi, T., O'Donnell, V., Schudel, A.A., 1998. Assessment using ELISA of the herd immunity levels induced in cattle by foot and mouth disease oil vaccines. Prev. Vet. Med 33, 283-296] while the cellular response was detected using an antigen specific lymphoproliferative test [Zamorano, P., Wigdorovitz, A., Chaher, M., Fernández, F., Sadir, A., Borca, M., 1994. Localization of B and T cell epitopes on a synthetic peptide containing the major immunogenic site of FMDV O1 Campos. Virology 201, 383-387]. The results show that, while no differences were detected in the cellular response, the anti-FMDV antibody reaction was significantly (<0.05) higher in animals immunized with the immunogen containing Avr. At 90 days post vaccination, 89-100% of the animals immunized with Avr presented predicted protection (PP) higher than 82% while just 50-61% of the animals immunized with vaccine without immunomodulator presented that characteristic. Also, it is shown that the increase in the anti-FMDV antibody titre in animals immunized with the vaccine containing Avr was mediated by an increase in the levels of both IgG1 and IgG2 which presented a significative correlation with LPELISA antibodies titres. It is concluded that the addition of Avr in the FMDV vaccines improve the immune status of the calves, the cattle population that suffers the highest epidemiological risk.

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Argentina.

Sixty-five sheep farms in the northern provinces of Buenos Aires, Entre Rios, Corrientes, Cordoba and Sante Fe were used in this survey on anthelmintic resistance. Anthelmintic groups tested were the benzimidazoles, levamisole, the combination levamisole + benzimidazole product and the avermectins. The overall level of resistance was 46% of properties, with resistance to the individual drug groups being 40%, 22%, 11% and 6%, respectively. On a large proportion of farms the resistance recorded was to two, or more, anthelmintic groups. Haemonchus contortus, Ostertagia spp. and Trichostrongylus spp. were the most abundant parasite species recorded. Resistance was greatest in the province of Corrientes where the frequency of treatment is generally high due to the endemic nature of H. contortus. Management practices were also important with resistance greatest on farms where frequent drenching is carried out and on farms carrying only sheep.

[Migration and mental disorders in the Chiraguano civilization]. / Migración y patología mental en la civilización de los chiriguanos.

The ethnographic characteristics of the Chiriguanos allowed us to make up an experimental design to show the relationship between migration and mental pathology. The Chiriguanos are a South American ethnographic population characterized by a traditional migratory tendency. The Chiriguanos group is a resultant of the Tupi-Guaraní migrations. From the 15th century up to the 19th aboriginal guaraníes moved from the current area of Paraguay to the East zone of Bolivia; they conquered and mixed with the group that lived there and after that they resisted the European forces. The Chiriguanos history can be divided in different phases: 1) The establishment in the new zone; 2) The "Chiriguana war" with the dominant group; 3) The grouping with Franciscan missions and its community organization. This study of Transcultural Psychiatry can be considered as an ex post facto experiment in the field of Psychiatric Epidemiology. It allows us to analyse population phenomena related to changes in the prevalence of mental pathology. The facts presented in this report have been established thanks to the use of sampling techniques adequated to each population being studied (original and migratory groups): demographic structure, total fertility Grow's "evolutional intensity index", and mental prevalence rates in both groups. Differences in the biennial prevalence rates of mental morbidity were found. In the original Chiriguana community there is an evident "group endogamy"; on the contrary, the migratory groups integrated by individuals of different aboriginal culture, are really melting-pots, that originate a new genetic groupal structure. We have worked with human situations created by a natural social and cultural reality. We have worked with two ethnographic homogeneous populations, one of them stable and the other a migratory one. We intended to demonstrate: 1) migration changes the rates of mental pathology; 2) those changes are followed by changes in the genetic structure of the individuals.

Migracion y patologia mental en la civilizacion de los chiriguanos. / Migration and mental pathology in the Chiriguanos civilization

Las caracteristicas etnograficas especiales de los aborigenes chiriguanos del Gran Chaco han permitido confeccionar un diseno de experimentos sobre migracion y patologia mental, mediante el cual se analizan algunos factores de genetica poblacional, poco estudiados en el campo de la investigacion psiquiatrica

Migración y patología mental en la civilización de los chiriguanos. / [Migration and mental disorders in the Chiraguano civilization]

The ethnographic characteristics of the Chiriguanos allowed us to make up an experimental design to show the relationship between migration and mental pathology. The Chiriguanos are a South American ethnographic population characterized by a traditional migratory tendency. The Chiriguanos group is a resultant of the Tupi-Guaraní migrations. From the 15th century up to the 19th aboriginal guaraníes moved from the current area of Paraguay to the East zone of Bolivia; they conquered and mixed with the group that lived there and after that they resisted the European forces. The Chiriguanos history can be divided in different phases: 1) The establishment in the new zone; 2) The [quot ]Chiriguana war[quot ] with the dominant group; 3) The grouping with Franciscan missions and its community organization. This study of Transcultural Psychiatry can be considered as an ex post facto experiment in the field of Psychiatric Epidemiology. It allows us to analyse population phenomena related to changes in the prevalence of mental pathology. The facts presented in this report have been established thanks to the use of sampling techniques adequated to each population being studied (original and migratory groups): demographic structure, total fertility Grows [quot ]evolutional intensity index[quot ], and mental prevalence rates in both groups. Differences in the biennial prevalence rates of mental morbidity were found. In the original Chiriguana community there is an evident [quot ]group endogamy[quot ]; on the contrary, the migratory groups integrated by individuals of different aboriginal culture, are really melting-pots, that originate a new genetic groupal structure. We have worked with human situations created by a natural social and cultural reality. We have worked with two ethnographic homogeneous populations, one of them stable and the other a migratory one. We intended to demonstrate: 1) migration changes the rates of mental pathology; 2) those changes are followed by changes in the genetic structure of the individuals.

Migracion y patologia mental en la civilizacion de los chiriguanos. / Migration and mental pathology in the Chiriguanos civilization

Las caracteristicas etnograficas especiales de los aborigenes chiriguanos del Gran Chaco han permitido confeccionar un diseno de experimentos sobre migracion y patologia mental, mediante el cual se analizan algunos factores de genetica poblacional, poco estudiados en el campo de la investigacion psiquiatrica

Effect of body fat distribution on the fatty acid composition of the depot fat of cattle.

The influence of liveweight, total carcass fat and the amount of fat at five specific anatomical locations on the fatty acid composition of the depot fat of adult ruminants was examined. The total carcassfat and the amount offat at specific locations seem to affect the fatty acid composition significantly. No important significant correlation between liveweight and fatty acid composition was found. There was an increase in odd, even and branched chain fatty acids, and a decrease in linoleic acid, with increase in animal age.