Metal loads and biomarker suite responses in a tropical carnivorous fish indicative of anthropogenic impacts in a Southeastern Brazilian lagoon.

Tropical coastal lagoons are highly productive environments exhibiting high biodiversity. However, the use of these ecosystems by local communities is of concern, since this generally leads to environmental degradation. The Imboassica coastal lagoon, located in Macaé city, in Northern Rio de Janeiro, is an important ecosystem in the state, however, already displaying signs of anthropogenic impacts. Carnivorous fish Hoplias malabaricus specimens were sampled from this impacted site, as well as from a reference area. Fish from Imboassica Lagoon presented lower condition factor, lower cholinesterase activity, and higher percentage of erythrocyte micronuclei when compared to fish from the reference site. Metals in fish from Imboassica Lagoon were always higher than Encantada Lagoon, with some seasonal differences, where some metals were higher in the rainy season compared to the dry season in muscle tissue, with the exception of Cu, Fe, Sr, and Zn; and in the liver, except for Ba, Cd, Cr, Ni, and Sr. Cr and Mn in the edible muscle portion of the fish were higher than the limits established by Brazilian and International legislations as permissible for human consumption, thus leading to concerns regarding public health risks for the local population that use fish as their main protein source.

Drought promotes increases in total mercury and methylmercury concentrations in fish from the lower Paraíba do Sul river, southeastern Brazil.

Bioaccumulation of mercury and methylmercury in fish represents a serious risk to human beings. Extreme climate events like droughts may increase the trophic transfer of contaminants and net methylation of mercury. The present study assessed the influence of the 2014 drought on total mercury and methylmercury levels in fish from the lower Paraiba do Sul river basin. Contaminant levels were compared for Pimelodus fur, Pachyurus adspersus, Pimelodella lateristriga, Oligosarcus hepsetus, and Crenicichla lacustris captured in five sites in 2013 (N = 212) and 2014 (N = 231). The results indicate that levels of contaminants were higher during the drought in most species. Rainfall was weakly and negatively correlated with total mercury levels in most of the species. The weak relationship between these two variables was due to the indirect influence of rainfall on mercury bioaccumulation. In summary, drought increased the levels of two contaminants in fish.

Organotropism of methylmercury in fish of the southeastern of Brazil.

This is one of the first studies to evaluate the effect of biometric variables (total length and weight), diet, and abiotic matrices (sediment and water column) on the bioaccumulation of methylmercury in tissues (muscle, liver, and gills) of four fish (two carnivore-invertivores, Pimelodus fur and Pachyurus adspersus; one carnivore-piscivore, Oligosarcus hepsetus; and one omnivore, Pimelodella lateristriga) in the lower section of a river in southeastern Brazil. Samples of fish (n = 120), water (n = 5) and sediment (n = 5) were collected at five sites characterized by pollution with mercury due to the use of organomercury fungicides and stream bed gold mining, commonly carried out in that section of the river in the 1980s. The results show that biometric variables are strongly correlated with methylmercury levels in muscle (r = 0.61, p < 0.0005) of P. fur. As a rule, concentrations of total mercury and methylmercury did not vary considerably between the organs of the species of different food habits, because of the environmental conditions in the study area. Despite the low concentrations of mercury in sediments (<0.05 mg kg-1 wet. wt), this compartment is a representative source of this pollutant for the organisms investigated, due to the close contact these animals keep with it in view of the low water columns in that section of the river.

Risk of ingesting As, Cd, and Pb in animal products in north Rio de Janeiro state, Brazil.

This study evaluated the levels of As, Cd, and Pb in muscle and liver the cattle and chicken. The risk was estimated for the adult population of a midsized city in southeast Brazil, concerning the tolerable ingestion and cancer risk. Samples of muscle and liver (cattle and chicken) were collected (n = 250). Samples of mineral supplements for cattle (n = 4) and chicken feed samples (n = 4) were evaluated as one of many potential source of contamination. Muscle, liver, mineral supplement, and feed samples were dissolved in acid medium and analyzed by ICP-OES. Daily muscle and liver intake was estimated using a questionnaire (N = 427). Daily intake of trace elements by the population based on the consumption of cattle muscle, cattle liver, chicken muscle, and chicken liver was low, corresponding to 2.76%, 0.33%, 2.12%, and 0.22% of the Tolerable Intake defined by the WHO for As; 0.54%, 0.29% 0.55%, 0.01%, for Cd; and 0.80%, 0.07%, 0.62%, 0.02%, for Pb. The mean of total ingestion of As, Cd and Pb was 5.43%, 1.18% and 1.51%, respectively of Tolerable Intake defined by WHO. Cancer risk was lower than 5 × 10-5 year-1. The results indicate that the muscle and liver consumption is a source of As, Cd, and Pb. Consumers that ingest cattle and chicken muscle need attention in terms the risk of cancer related to intake of As and Cd. Feed and mineral supplementation remain as one of many sources of exposure of As, Cd, and Pb.

Spatial-temporal dynamics and sources of total Hg in a hydroelectric reservoir in the Western Amazon, Brazil.

Damming rivers to construct hydroelectric reservoirs results in a series of impacts on the biogeochemical Hg cycle. For example, modifying the hydrodynamics of a natural watercourse can result in the suspension and transport of Hg deposits in the water column, which represents an exposure risk for biota. The objective of this study was to evaluate the influences of seasonality on the dispersion of total Hg in the Hydroelectric Power Plant (HPP)-Samuel Reservoir (Porto Velho/Brazil). Sampling campaigns were performed during the three following hydrological periods characteristic of the region: low (Oct/2011), ebbing (May/2012), and high (Feb/2013) water. Sediment profiles, suspended particulate matter (SPM), and aquatic macrophytes (Eicchornia crassipes and Oryza spp.) were collected, and their Hg concentrations and isotopic and elemental C and N signatures were determined. The drainage basin significantly influenced the SPM compositions during all the periods, with a small autochthonous influence from the reservoir during the low water. The highest SPM Hg concentrations inside the reservoir were observed during the high water period, suggesting that the hydrodynamics of this environment favor the suspension of fine SPM, which has a higher Hg adsorption capacity. The Hg concentrations in the sediment profiles were ten times lower than those in the SPM, indicating that large particles with low Hg concentrations were deposited to form the bottom sediment. Hg concentrations were higher in aquatic macrophyte roots than in their leaves and appeared to contribute to the formation of SPM during the low water period. In this environment, Hg transport mainly occurs in SPM from the Jamari River drainage basin, which is the primary source of Hg in this environment.

The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes.

Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.

Mutational characterization of the P3H1/CRTAP/CypB complex in recessive osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone deformities and fractures. Most cases are caused by autosomal dominant mutations in the type I collagen genes COL1A1 and COL1A2; however, an increasing number of recessive mutations in other genes have been reported. The LEPRE1, CRTAP, and PPIB genes encode proteins that form the P3H1/CRTAP/CypB complex, which is responsible for posttranslational modifications of type I collagen. In general, mutations in these genes lead to severe and lethal phenotypes of recessive OI. Here, we describe sixteen genetic variations detected in LEPRE1, CRTAP, and PPIB from 25 Brazilian patients with OI. Samples were screened for mutations on single-strand conformation polymorphism gels and variants were determined by automated sequencing. Seven variants were detected in patients but were absent in control samples. LEPRE1 contained the highest number of variants, including the previously described West African allele (c.1080+1G>T) found in one patient with severe OI as well as a previously undescribed p.Trp675Leu change that is predicted to be disease causing. In CRTAP, one patient carried the c.558A>G homozygous mutation, predicted as disease causing through alteration of a splice site. Genetic variations detected in the PPIB gene are probably not pathogenic due to their localization or because of their synonymous effect. This study enhances our knowledge about the mutational pattern of the LEPRE1, CRTAP, and PPIB genes. In addition, the results strengthen the proposition that LEPRE1 should be the first gene analyzed in mutation detection studies in patients with recessive OI.

Food preferences and Hg distribution in Chelonia mydas assessed by stable isotopes.

Mercury (Hg) is a highly toxic pollutant that poses in risk several marine animals, including green turtles (Chelonia mydas). Green turtles are globally endangered sea turtle species that occurs in Brazilian coastal waters as a number of life stage classes (i.e., foraging juveniles and nesting adults). We assessed total Hg concentrations and isotopic signatures ((13)C and (15)N) in muscle, kidney, liver and scute of juvenile green turtles and their food items from two foraging grounds with different urban and industrial development. We found similar food preferences in specimens from both areas but variable Hg levels in tissues reflecting the influence of local Hg backgrounds in food items. Some juvenile green turtles from the highly industrialized foraging ground presented liver Hg levels among the highest ever reported for this species. Our results suggest that juvenile foraging green turtles are exposed to Hg burdens from locally anthropogenic activities in coastal areas.

Estatinas x ácido lipóico na prevenção e tratamento das doenças cardiovasculares / Statins x lipoic acid in the prevention and treatment of cardiovascular diseases

Cardiovascular diseases (CVD) are the leading cause of death worldwide and atherosclerosis is the most important process underlying CVD. Statins are widely used in primary and secondary prevention of CVD, though their adverse side effects, such as myopathy and hepatotoxicity, justify the search for therapeutic alternatives. Alpha lipoic acid is a potent antioxidantand its potential use to combat various conditions, such as diabetic nephropathy, metal poisoning, Alzheimer's disease and CVD has been under intense study. The aim of this review was to gather information on the use of statins and alpha lipoic acid in the prevention and treatment of CVD. The literature suggests that inaddition to the known side effects most associated with the use of statins, they can also cause reduced levels of coenzyme Q10 (CoQ10), an important mitochondrial antioxidant and electron transport chain carrier that has the capacity to antagonize oxidation of plasma lowdensity lipoprotein (LDL). The loss of CoQ10 can reduce adenosine triphosphate (ATP) levels in cardiac cells, further worsening the overall state of the individual. Alpha lipoic acid produces favorable metabolic and endothelial anti-inflammatory effects, without adverse side effects, and thus may be an alternative treatment for the prevention of CVD. However, more controlled clinical studies are needed to establish definitively the prophylactic and therapeutic potential of alpha lipoic acid and to decide whether it might be more effective than statins for the prevention and treatment of CVD...

As doenças cardiovasculares (DCVs) são a principal causa de morte no mundo e tem a aterosclerose como componente mais importante. As estatinas são extensamente utilizadas na prevenção primária e secundária das DCVs, todavia seus efeitos adversos como miopatia e toxicidade hepática justificam a busca por alternativas terapêuticas. O ácido lipóico é um potente antioxidante e vem sendo intensamente investigado no combate de diversas condições tais como nefropatia diabética, intoxicação por metais, doença de Alzheimer e nas DCVs. O objetivo desta revisão foi reunir informações acerca da utilização das estatinas e do ácido lipóico na prevenção e tratamento das DCVs. A literatura aponta que além dos efeitos adversos mais conhecidos associados ao uso das estatinas, elas também podem ocasionar a redução dos níveis de Coenzima Q10 (CoQ10), um importante antioxidante mitocondrial e transportador de elétrons, que possui a capacidade de antagonizar a oxidação da Lipoproteína de Baixa Densidade (LDL) plasmática. Ainda, a deficiência da CoQ10, por sua vez, pode levar a diminuição da adenosina trifosfato (ATP) nas células cardíacas, comprometendo ainda mais o estado global do indivíduo. Enquanto isso, o ácido lipóico apresenta favoráveis efeitos antiinflamatórios, metabólicos e endoteliais, contudo sem a presença de efeitos adversos, podendo ser uma opção terapêutica na prevenção das DCVs. Entretanto, mais estudos clínicos controlados são necessários para estabelecer de maneira definitiva os potenciais terapêuticos e profiláticos do ácido lipóico, avaliando se ele pode ser mais efetivo para a prevenção e tratamento das DCVs do que as estatinas...

MSX1 gene polymorphisms in non-syndromic cleft lip and/or palate.

OBJECTIVE: The aim of this study was to investigate the contribution of 6 polymorphic variants of the MSX1 gene in non-syndromic cleft lip and/or palate (NSCL/P). METHODS: Three hundred and fifty-eight individuals (158 NSCL/P cases and 200 controls) were genotyped by TaqMan allelic discrimination using predesigned SNP assays. Statistical analyses were conducted using the software spss 15.0 and the r statistical suite. Haplotype block structure and haplotype frequencies were determined using the Haploview. A P-value of 0.05 and confidence interval of 95% were used for all of statistical tests. RESULTS: The patients with non-syndromic cleft lip and/or palate were characterized by similar distribution of MSX1 genotypes and allele in comparison to subjects without oral clefts (P > 0.05). Two haplotype blocks were constructed with polymorphisms of MSX1 gene and haplotypes formed showed a similar frequency in patients with and without oral clefts. CONCLUSIONS: The present study provides no evidence that MSX1 polymorphisms (rs3775261, rs1042484, rs12532, rs6446693, rs4464513 and rs1907998) play a major role in NSCL/P.

Bactérias envolvidas nas mastites subclínicas de cabra da região de Salvador, Bahia / Bacteria involved in subclinical mastitis in goats in the region of Salvador, Bahia, Brazil

A mastite é uma infecção frequente da glândula mamária, sendo a principal doença que afeta o úbere das fêmeas e responsável pelos maiores prejuízos à produção leiteira em caprinos, reduzindo em quantidade e depreciando a qualidade do leite e seus derivados. Nesse estudo foram colhidas amostras de leite de cabras com reação positiva ao CMT, em propriedades localizadas em Bonfim de Feira, Barra do Pojuca, Feira de Santana, Camaçari, Anguera e Antônio Cardoso, todas próximas à Cidade de Salvador, Bahia. Do material coletado foi realizado cultivo bacteriológico em ágar sangue de ovino a 10%, ágar McConkey e também enriquecido em caldo BHI. O Staphylococcus spp. foi a bactéria de maior prevalência (90,3%), seguida de Streptococcus (4,8%), Micrococcus (1,6%) e Enterobacter (1,6%). Todas as bactérias foram submetidas ao teste de sensibilidade aos antimicrobianospelo método de difusão em disco, sendo que 54,1% das estirpes estudadas apresentaram sensibilidade a todas as drogas testadas, e 45,9% das estirpes identificadas apresentaram resistência a pelo menos um dos antimicrobianos. O presente estudo confirmou o Staphylococcus spp. como a principal bactéria envolvida na etiologia das mastites subclínicas caprinas.

Bacteria involved in subclinical mastitis in goats in the region of Salvador, Bahia, Brazil. Mastitis is a common infection of the mammary gland, the main disease affecting the udder of females, and responsible for major losses in milk production in goats, decreasing the quantity and quality of the milk and its derivatives. In this study milk samples were collected from goats with positive reaction to CMT in properties located in Bonfim de Feira, Barra do Pojuca, Feira de Santana, Camaçari, Anguera and Antônio Cardoso, all of which are places surrounding the city of Salvador, Bahia, Brazil. The samples were submitted to bacteriological culture carried out in agar with 10% sheep blood, McConkey agar, and agar enriched with BHI broth. Staphylococcus spp. bacteria was the most prevalent (90.3%), followed by Streptococcus (4.8%), Micrococcus (1.6%) and Enterobacter (1.6%). All bacteria were subjected to antimicrobial susceptibility testing by the disc diffusion method, revealing that 54.1% of the strains studied were sensitive to all drugs tested, while 45.9% of identified strains showed resistance to at least one of antimicrobials. The present studyconfirmed Staphylococcus spp. as the main bacteria involved in the etiology of subclinical goat mastitis.

Levels of oxidative stress markers: correlation with hepatic function and worm burden patients with schistosomiasis.

Schistosomiasis is caused by Schistosoma mansoni and is a public health problem in Brazil. The typical granulomatous lesion is associated with the increase in the oxidative damage by generation of free radicals. The aim of this work was to correlate some oxidative stress markers with the worm burden on carriers of schistosomiasis (n = 30) in the acute phase in comparison to healthy subjects (n = 30). The pro-oxidant parameter used was the colorimetric quantification of reactive substances to thiobarbituric acid, while the antioxidant markers used were blood content of reduced glutathione and determination of the activity of catalase. The worm burden was assessed by Kato-Katz method. The results pointed out that initially there was no difference in the catalase activity. However, there was a positive correlation between the increase in parasitic load and intensity of lipid peroxidation, and decrease in the content of reduced glutathione. Additionally, only the aspartate aminotransferase levels presented to be high, while there was a decrease in bilirubin level. Therefore, a possible association between the establishment of the oxidative stress in tissue and the parasitic load of Schistosoma mansoni is suggested.

Cooperative use of cytochrome cd1 nitrite reductase and its redox partner cytochrome c552 to improve the selectivity of nitrite biosensing.

In this work, a novel enzymatic biosensor for determination of nitrites constructed on an electrochemical transducing platform is proposed. The sensor is based on cytochrome-cd(1) (cyt-cd(1)) nitrite reductase from Marinobacter hydrocarbonoclasticus strain 617 as biological recognition element, and its putative physiological redox partner cytochrome-c(552) (cyt-c(552)), as electron mediator. The proteins were co-immobilized using a photopolymerizable polyvinyl alcohol (PVA) derivative, onto carbon paste screen printed electrodes (CPSPEs); the optimal modification conditions were 100 µM cyt-cd(1)/100 µM cyt-c(552) and 50% PVA, after a 48 h polymerization time. Electrochemical characterization of the mediator was carried out by cyclic voltammetry. The one-electron exchange between cyt-c(552) and the working electrode is a quasi-reversible process, without mass transport limitations. The formal potential of the mediator is 254±2 mV vs NHE and the intermolecular electron transfer rate constant between cytochromes c(552) and cd(1) is 9.9×10(3)M(-1)s(-1). The analytical parameters of the biosensor response to nitrite as assessed by amperometric measurements were: linear range from 10 to 200 µM; detection and quantification limits of 7 and 24 µM, respectively; sensitivity of 2.49±0.08 Amol(-1)cm(2) µM(-1). Catalytic profiles in the presence of possible interfering species were also investigated. The interference from competitive enzymatic reduction of dissolved oxygen could be overcome by tuning the cyclic voltammograms for faster sweep rates.

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.

Tuberculin skin testing in HIV-infected patients in Campo Grande, Mato Grosso do Sul State, Brazil

A cross-sectional study on HIV/AIDS was carried out in 108 outpatients from the university hospital of the Federal University of Mato Grosso do Sul, Campo Grande, Brazil, from July to December 2008, to investigate latent tuberculosis infection using the tuberculin skin test (TST). The prevalence of positive results was 13.9 percent. The CD4+ T cell count (p = 0.091) and the diagnosis time (p = 0.010) were statistically significant when compared with TST positivity. In the cohort of HIV/AIDS patients who had latent tuberculosis infection, the median diagnosis time was eight years. Undetectable viral load presented significant association (p = 0.046) with tuberculosis infection. The fact that numerous individuals with HIV/AIDS infection presented a negative reaction to the tuberculin skin test is probably related to alterations in the cellular immune response induced by HIV infection. The tuberculin test is a useful tool for the detection of latent tuberculosis infection and should be performed in all HIV/AIDS individuals at the time of the diagnosis and on a yearly basis, if negative. Both the early identification of the tuberculosis infection by the tuberculin skin test at the moment of immunological restoration and chemoprophylaxis in infected individuals are mechanisms to control HIV/AIDS and tuberculosis coinfection.

Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-γ genes and its association with susceptibility to tuberculosis: [review]

Mycobacterium tuberculosis kills more people than any other single pathogen, with an estimated one-third of the world's population being infected. Among those infected, only 10 percent will develop the disease. There are several demonstrations that susceptibility to tuberculosis is linked to host genetic factors in twins, family and associated-based case control studies. In the past years, there has been dramatic improvement in our understanding of the role of innate and adaptive immunity in the human host defense to tuberculosis. To date, attention has been paid to the role of genetic host and parasitic factors in tuberculosis pathogenesis mainly regarding innate and adaptive immune responses and their complex interactions. Many studies have focused on the candidate genes for tuberculosis susceptibility ranging from those expressed in several cells from the innate or adaptive immune system such as Toll-like receptors, cytokines (TNF-α, TGF-β, IFN-γ, IL-1b, IL-1RA, IL-12, IL-10), nitric oxide synthase and vitamin D, both nuclear receptors and their carrier, the vitamin D-binding protein (VDBP). The identification of possible genes that can promote resistance or susceptibility to tuberculosis could be the first step to understanding disease pathogenesis and can help to identify new tools for treatment and vaccine development. Thus, in this mini-review, we summarize the current state of investigation on some of the genetic determinants, such as the candidate polymorphisms of vitamin D, VDBP, Toll-like receptor, nitric oxide synthase 2 and interferon-γ genes, to generate resistance or susceptibility to M. tuberculosis infection.

Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-gamma genes and its association with susceptibility to tuberculosis.

Mycobacterium tuberculosis kills more people than any other single pathogen, with an estimated one-third of the world's population being infected. Among those infected, only 10% will develop the disease. There are several demonstrations that susceptibility to tuberculosis is linked to host genetic factors in twins, family and associated-based case control studies. In the past years, there has been dramatic improvement in our understanding of the role of innate and adaptive immunity in the human host defense to tuberculosis. To date, attention has been paid to the role of genetic host and parasitic factors in tuberculosis pathogenesis mainly regarding innate and adaptive immune responses and their complex interactions. Many studies have focused on the candidate genes for tuberculosis susceptibility ranging from those expressed in several cells from the innate or adaptive immune system such as Toll-like receptors, cytokines (TNF-alpha, TGF-beta, IFN-gamma, IL-1b, IL-1RA, IL-12, IL-10), nitric oxide synthase and vitamin D, both nuclear receptors and their carrier, the vitamin D-binding protein (VDBP). The identification of possible genes that can promote resistance or susceptibility to tuberculosis could be the first step to understanding disease pathogenesis and can help to identify new tools for treatment and vaccine development. Thus, in this mini-review, we summarize the current state of investigation on some of the genetic determinants, such as the candidate polymorphisms of vitamin D, VDBP, Toll-like receptor, nitric oxide synthase 2 and interferon-gamma genes, to generate resistance or susceptibility to M. tuberculosis infection.

A novel COL1A1 gene-splicing mutation (c.1875+1G>C) in a Brazilian patient with osteogenesis imperfecta.

Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility and deformity, recurrent fractures, blue sclera, short stature, and dentinogenesis imperfecta. Most cases are caused by mutations in COL1A1 and COL1A2 genes. We present a novel splicing mutation in the COL1A1 gene (c.1875+1G>C) in a 16-year-old Brazilian boy diagnosed as a type III osteogenesis imperfecta patient. This splicing mutation and its association with clinical phenotypes will be submitted to the reference database of COL1A1 mutations, which has no other description of this mutation.

In situ detection of SOCS and cytokine expression in the uterine cervix from HIV/HPV coinfected women.

The purpose of this study was to look for associations between a newly described class of suppressors of cytokine signaling (SSI/SOCS) and cytokine expression in the uterine cervix from HIV/HPV coinfected women. We examined the pro-inflammatory cytokines TNF-alpha and IL-6 since their expressions are linked and responsible for many aspects of both localized and systemic inflammatory responses. Further, expression of SSI/SOCS has been implicated in the negative feedback regulation of cytokine receptor signaling. PCR-amplified HIV-1 cDNA was noted mainly in the stroma, showing a perivascular distribution, and most of the infected cells colabeled with the macrophage marker CD68. The distribution of IL-6 and TNF-alpha was in the same area to HIV-1 and much greater than normal cervices from women with no evidence of viral infection. SOCS/SSI-1 and -3 mRNA positive cells in the uterine cervix were commonly detected in these noninfected cervical tissues; however, very few cells that contained SOCS were evident in areas where HIV-1, TNF-alpha, and IL-6 expressing cells were found. This suggests that viral-related suppression of SOCS/SSI-1-3 expression may be a factor in the marked local enhancement of TNF-alpha and IL-6 production which, in turn, may help facilitate viral spread; however, further studies should be done in order to elucidate the exact mechanisms of SOCS in the cervix.

Turnera ulmifolia L. (Turneraceae): preliminary study of its antioxidant activity.

Turnera ulmifolia L. is used in Brazilian folk medicine as an anti-inflammatory. Since this activity may be correlated with the presence of antioxidant compounds, a leaf extract was evaluated for its radical scavenging capacity (RSC). The in vitro RSC of a 50% hydroethanolic (HE) extract was evaluated by beta-carotene/linoleic acid coupled oxidation system for the inhibition of oxidation and the lipid peroxidation inhibition in rat brain homogenates, using thiobarbituric acid reactive substances (TBARS) and chemiluminescence (CL). Results indicated, through peroxidation suppression, that this extract exhibited greater antioxidative activity (77.4% +/- 10%) than alpha-tocopherol (58.4% +/- 3.7%). TBARS and CL inhibition was concentration-dependent and Q(1/2) values were 8.2 and 6.0 microg/mL for TBARS and CL, respectively. For alpha-tocopherol these values were 7.1 microg/mL (TBARS) and 9.8 microg/mL (CL). Phenolic compounds may be responsible for this antioxidant capacity.