Systemic lupus erythematosus: Association with KIR and SLC11A1 polymorphisms, ethnic predisposition and influence in clinical manifestations at onset revealed by ancestry genetic markers in an urban Brazilian population

Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belem, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3`UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations. Lupus (2011) 20, 265-273.

Analysis of five polymorphic DNA markers for indirect genetic diagnosis of haemophilia A in the Brazilian population

Hemophilia A is an X-linked, inherited, bleeding disorder caused by the partial or total inactivity of the coagulation factor VIII (FVIII). Due to difficulties in the direct recognition of the disease-associated mutation in the F8 gene, indirect diagnosis using polymorphic markers located inside or close to the gene is used as an alternative for determining the segregation of the mutant gene within families and thus for detecting carrier individuals and/or assisting in prenatal diagnosis. This study characterizes the allelic and haplotype frequencies, genetic diversity, population differentiation and linkage disequilibrium of five microsatellites (F8Int1, F8Int13, F8Int22, F8Int25.3 and IKBKG) in samples of healthy individuals from Sao Paulo, Rio Grande do Sul and Pernambuco and of patients from Sao Paulo with haemophilia A to determine the degree of informativeness of these microsatellites for diagnostic purposes. The interpopulational diversity parameters highlight the differences among the analyzed population samples. Regional differences in allelic frequencies must be taken into account when conducting indirect diagnosis of haemophilia A. With the exception of IKBKG, all of the microsatellites presented high heterozygosity levels. Using the markers described, diagnosis was possible in 10 of 11 families. The F8Int22, F8Int1, F8Int13, F8Int25.3 and IKBKG microsatellites were informative in seven, six, five and two of the cases, respectively, demonstrating the effectiveness of using these microsatellites in prenatal diagnosis and in carrier identification in the Brazilian population.

Mothers of children with cerebral palsy with or without epilepsy: a quality of life perspective

Methods. aEuro integral Thirty mothers of disabled children participated in the study. The control group comprised of 18 healthy mothers of children without disabilities. All mothers agreed to participate in the study. They completed the evaluation forms of the SF-36 health survey, a well-documented, self-administered QOL scoring system. Results. aEuro integral The results of our study support the premise that mothers of children with CP, as a group, have poorer QOL than mothers of not disabled children. Conclusions. aEuro integral We also observed that mothers of children with CP and epilepsy have poorer QOL than mothers of children with CP without epilepsy.

Interchangeability among therapeutics equivalents of lamotrigine in the treatment of refractory epilepsy patients: risks and benefits

Introduction. Epilepsy is a condition characterized by signs and symptoms of neurological disorder. Lamotrigine has been widely used, mainly due to their greater tolerability and lower rate of drug interactions with other antiepileptic drugs however the newest antiepileptic drugs have high cost to patient. In Brazil there are three different sort of pharmaceutical equivalents (reference, generic and similar), and the Brazilian health care authorities offers to users the possibility to receive them free of charge. Moreover these pharmaceutical equivalents can change during the treatment of epilepsy because this authorities buy the cheapest by public tender two or three times a year. Aim. To evaluate the clinical and laboratory findings related to the most frequently used therapeutic equivalents of lamotrigine (reference drugs and similar products). Patients and methods. Two similar formulations (A and B) and one reference (C) were tested in nine epileptic refractory patients. The study was divided into three periods of 42 days, one for each formulation, and medical data about the frequency of seizures, the occurrence of side effects and measurement of plasma concentrations of lamotrigine were collected. Results. The average number of seizures/week and plasma concentration of lamotrigine for formulations A, B and C were not statistically significant differences. Three patients during the use of the formulation C presented mild and transitory side effects. Conclusion. Similar or reference drugs showed satisfactory results, however the interchangeability among the formulations raise the difficulty for the management of seizures in refractory epilepsy.

Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids

Studies have provided evidence of the important effects of omega-3 fatty acid on the brain in neurological conditions, including epilepsy. Previous data have indicated that omega-3 fatty acids lead to prevention of status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy. Omega-3 fatty acid supplementation has resulted in extensive preservation of GABAergic cells in animals with epilepsy. This study investigated the interplay of these effects with neurogenesis and brain-derived neurotrophic factor (BDNF). The results clearly showed a positive effect of long-term omega-3 fatty acid supplementation on brain plasticity in animals with epilepsy. Enhanced hippocampal neurogenesis and BDNF levels and preservation of interneurons expressing parvalbumin were observed. Parvalbumin-positive cells were identified as surviving instead of newly formed cells. Additional investigations are needed to determine the electrophysiological properties of the newly formed cells and to clarify whether the effects of omega-3 fatty acids on brain plasticity are accompanied by functional gain in animals with epilepsy. (C) 2009 Elsevier Inc. All rights reserved.

Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: A case study

Epilepsy is the most common neurological disorder in both dogs and humans. Although the pharmacological options for treatment of epilepsies have increased. it has been reported that two-thirds of dogs with epilepsy are refractory to antiepileptic drug therapy. To our knowledge, there are no experimental Studies in the literature that show an effect of omega-3 supplementation oil epilepsy in dogs. Our case study describes the effectiveness of daily intake of a moderate amount of fish oil in a case of canine epilepsy. (C) 2009 Elsevier Inc. All rights reserved.

Could sudden death syndrome (SDS) in chickens (Gallus gallus) be a valid animal model for sudden unexpected death in epilepsy (SUDEP)?

Epilepsy is the most common serious neurological disorder and approximately 1% of the population worldwide has epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning fisk factors for SUDEP is conflicting, but potential risk factors include: young age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Similarly, sudden death syndrome (SDS) is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings and incidence of SDS these animals has recently increased worldwide. Moreover, the exactly cause of SDS in Gallus gallus is unknown, but is very probable that cardiac abnormalities play a potential role. Due the similarities between SUDEP and SDS and as Gallus gallus behavioral manifestation during SDS phenomenon is close of a tonic-clonic seizure, in this paper we suggest that epilepsy could be a new possible causal factor for SDS. (C) 2009 Elsevier Ltd. All rights reserved.

Isolation and genetic characterisation of Toxoplasma gondii from a red-handed howler monkey (Alouatta belzebul), a jaguarundi (Puma yagouaroundi), and a black-eared opossum (Didelphis aurita) from Brazil

Toxoplasma gondii isolates are highly diverse in domestic animals from Brazil. However, little is known about the genetics of this parasite from wild mammals in the same region. Reveal genetic similarity or difference of T. gondii among different animal populations is necessary for us to understand transmission of this parasite. Here we reported isolation and genetic characterisation of three T. gondii isolates from wild animals in Brazil. The parasite was isolated by bioassay in mice from tissues of a young male red handed howler monkey (Alouatta belzebul), an adult male jaguarundi (Puma yagouaroundi), and an adult female black-eared opossum (Didelphis aurita). The monkey and the jaguarundi had inhabited the Zoo of Parque Estadual Dois Irmaos, Pernambuco State, Northeastern Brazil, for 1 year and 8 years, respectively. The wild black-eared opossum was captured in Sao Paulo State, Southeastern Brazil, and euthanised for this study because it was seropositive for T. gondii (titre 1:100 by the modified agglutination test, MAT). Ten PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) markers, SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico, were used to genotype the isolates. T. gondii was isolated from the brain and heart homogenate of the monkey, the muscle homogenate of the jaguarundi, and the heart homogenate of the black-eared opossum. This was the first isolation of T. gondii from a neotropical fetid from Brazil. The isolate from the monkey (TgRhHmBr1) was not virulent in mice, whereas the isolates from the jaguarundi (TgJagBr1) and the black-eared opossum (TgOpBr1) were virulent in mice. The genotype of the isolate from the monkey has been identified in isolates from a goat and ten chickens in the same region of Brazil, suggesting that it may be a common lineage circulating in this region. The genotypes of the isolates from the jaguarundi and the black-eared opossum have not been previously reported. Although there are already 88 genotypes identified from a variety of animal hosts in Brazil, new genotypes are continuously being identified from different animal species, indicating an extremely high diversity of T. gondii in the population. (C) 2010 Elsevier B.V. All rights reserved.

Genetic analysis of ticks belonging to the Rhipicephalus sanguineus group in Latin America

Phylogenetic analyses based on mitochondrial 16S rDNA sequences were generated from Rhipicephalus sanguineus group specimens collected in 29 localities among 9 Latin-American countries, plus ticks collected in South Africa, Spain, and Italy. Sequences from Latin America generated six different haplotypes (A, B, C, D, E, and F). Phylogenetic analyses generated trees that segregated our tick sequences into two distinct clades: one is represented by haplotypes A-C, and South African R. sanguineus and Rhipicephalus turanicus ticks; the second clade is represented by haplotypes D-F, and European R. sanguineus and R. turanicus ticks. When haplotypes A-Fare plotted in the Latin America map according to their geographical coordinates, it is clearly seen that haplotypes D-F are restricted to the southern portion of this continent, whereas haplotypes A-C are distributed in areas between northern Mexico and Brazil (except for the extreme south of this last country, where haplotype E was present). Hence, our phylogenetic analyses separated New World specimens of R. sanguineus into two distinct clades, one represented by tropical and subtropical populations (haplotypes A-C), here designated as the `tropical` species. On the other hand, haplotypes D-F are here designated as the `temperate` species because of their distribution in the southern portion of South America. Until recently, it was assumed that the R. sanguineus group was represented by a single species in the New World, namely R. sanguineus. While the present results coupled with recent studies support the presence of at least two species under the taxon R. sanguineus in the New World, they also show that even in the Old World, the taxon R. sanguineus might be represented by more than one species, since our phylogenetic analysis segregated European and South African R. sanguineus ticks into two distinct clades. The same can be applied for Spanish and South African R. turanicus. (C) 2010 Elsevier B.V. All rights reserved.

Genetic diversity among Toxoplasma gondii isolates of small ruminants from Brazil: Novel genotypes revealed

Recent studies indicated that Toxoplasma gondii isolates of many domestic animal hosts from Brazil are genetically and biologically different from those in USA and Europe. Despite of high pathogenicity of this parasite to small ruminants, the epidemiology and genetic diversity of T. gondii in these animals are not well understood in Brazil. In this study, a total of 28 T. gondii samples (16 isolates from sheep in Sao Paulo state, and 12 isolates from goats in the states of Sao Paulo and Rio Grande do Norte) were genotyped using genetic markers SAG1, SAG2, SAG3, BTUB, CRAG, c22-8, c29-2, L358, PK1, Apico and CS3. Eleven genotypes were identified from these T. gondii isolates. Eight isolates (4 from sheep and 4 from goats) were grouped into the common clonal type Brl lineage. One sheep isolate was grouped to the type BrIII lineage. Five isolates grouped to three previously identified genotypes in Brazil, and 13 isolates grouped to six novel genotypes. Mixed genotype was found in one isolate from goat in Sao Paulo. No classical clonal Type I. II or III isolates were found, confirming previous reports that these clonal lineages are rare in Brazil. The allele types at the CS3 locus are strongly linked to mouse virulence of the parasite. The results of this study indicate that even though a large number of T. gondii genotypes have been identified from a variety of animal hosts in Brazil, high percentage of new genotypes are continuously identified from different animal species, suggesting extremely high diversity of T. gondii in the population. (C) 2010 Elsevier B.V. All rights reserved.

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

FAPESP (the Sao Paulo State research funding foundation)

Low genetic diversities of rabies virus populations within different hosts in Brazil

The low rates of nonsynonymous evolution observed in natural rabies virus (RABV) isolates are suggested to have arisen in association with the structural and functional constraints operating on the virus protein and the infection strategies employed by RABV within infected hosts to avoid strong selection by the immune response. In order to investigate the relationship between the genetic characteristics of RABV populations within hosts and the virus evolution, the present study examined the genetic heterogeneities of RABV populations within naturally infected dogs and foxes in Brazil, as well as those of bat RABV populations that were passaged once in suckling mice. Sequence analyses of complete RABV glycoprotein (G) genes showed that RABV populations within infected hosts were genetically highly homogeneous whether they were infected naturally or experimentally (nucleotide diversities of 0-0.95 x 10(-3)). In addition, amino acid mutations were randomly distributed over the entire region of the G protein, and the nonsynonymous/synonymous rate ratios (d(N)/d(S)) for the G protein gene were less than 1. These findings suggest that the low genetic diversities of RABV populations within hosts reflect the stabilizing selection operating on the virus, the infection strategies of the virus, and eventually, the evolutionary patterns of the virus. (C) 2009 Elsevier B.V. All rights reserved.

Socioeconomic causes of loss of animal genetic diversity: Analysis and assessment

The number of breeds of domesticated animals, especially livestock, have declined rapidly. The proximate causes and processes involved in loss of breeds are outlined. The path-dependent effect and Swanson's dominance-effect are discussed in relation to breed selection. While these help to explain genetic erosion, they need to be supplemented to provide a further explanation of biodiversity loss. It is shown that the extension of markets and economic globalisation have contributed significantly to genetic loss of breeds. In addition, the decoupling of animal husbandry from surrounding natural environmental conditions is further eroding the stock of genetic resources, particularly industrialised intensive animal husbandry. Recent trends in animal husbandry raise very serious sustainability issues, apart from animal welfare concerns.