The genetic influence of the brain-derived neurotrophic factor Val66Met polymorphism in chronic low back pain

Abstract Background: The Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene is a potential biomarker of vulnerability to pain. Thus, the present study aimed to investigate the association of this polymorphism with clinical and biopsychosocial factors in patients with chronic low back pain (CLBP). Methods: A total of 107 individuals with CLBP answered questionnaires that were validated and adapted for the Brazilian population, including the Brief Inventory of Pain, the Central Sensitization Inventory, the Roland Morris Disability Questionnaire, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, the Survey of Pain Attitude-Brief, and the Hospital Anxiety and Depression Scale. All of the subjects were genotyped for the BDNF Val66Met polymorphism. Results: The sample showed moderate scores of disability, central sensitization, and kinesiophobia, in addition to mild anxiety, hopelessness, and ruminant thoughts. No significant association was observed between the Val66Met polymorphism and the variables analyzed. Besides, there was no relationship between the BDNF Val66Met polymorphism with CSI, catastrophization, or disabilities that were generated by CLBP. Conclusions: The results showed that the Val66Met polymorphism of the BDNF gene was not associated with clinical and biopsychosocial characteristics of CLBP in the sample studied.

Valor prognóstico das concentrações precoces de metaloproteinases -2 e -9 após traumatismo craniencefálico grave / Prognostic utility of early plasma matrix metalloproteinases -2 and -9 concentrations after severe traumatic brain injury

RESUMO Objetivo: Determinar se os níveis plasmáticos das metaloproteinases de matriz -2 e -9 tem associação com a mortalidade na unidade de terapia intensiva em pacientes com trauma craniencefálico grave, independentemente de lesões não cerebrais associadas. Métodos: Esta coorte prospectiva incluiu 39 pacientes do sexo masculino com trauma craniencefálico grave (escore na escala de coma Glasgow na admissão hospitalar: 3 - 8). Os níveis plasmáticos das metaloproteinases -2 e -9 foram determinados por ELISA no momento da admissão na unidade de terapia intensiva. Resultados: O trauma craniencefálico grave apresentou mortalidade de 46% na unidade de terapia intensiva. Concentrações mais elevadas de metaloproteinase -9 apresentaram associação com a mortalidade: 147,94 ± 18,00ng/mL para pacientes que sobreviveram e 224,23 ± 23,86ng/mL para os que não sobreviveram (média ± erro padrão, respectivamente; p = 0,022). Todavia, não houve associação significativa entre os níveis de metaloproteinase -2 e a mortalidade na unidade de terapia intensiva: 315,68 ± 22,90ng/mL para o grupo de sobreviventes e 336,55 ± 24,29ng/mL entre os pacientes que não sobreviveram (p = 0,499). Além disso, não se observaram associações significativas entre os níveis de metaloproteinase -2 (p = 0,711) ou metaloproteinase -9 (p = 0,092) e a presença de lesões não cerebrais associadas. Conclusão: Em vítimas de traumatismo craniencefálico grave, níveis elevados de metaloproteinase -9 tiveram valor preditivo para o desfecho fatal na unidade de terapia intensiva independentemente da presença de lesões não cerebrais associadas. Por outro lado, no mesmo cenário, os níveis plasmáticos de metaloproteinase -2 não apresentaram associação com a mortalidade na unidade de terapia intensiva

Abstract Objective: To determine whether the matrix metalloproteinases-2 and -9 plasma levels were associated with intensive care unit mortality in patients who suffered severe traumatic brain injury, despite the presence of extracerebral injuries. Methods: This prospective cohort enrolled 39 male patients who suffered severe traumatic brain injury (Glasgow coma scale: 3 - 8 at hospital admission). The plasma matrix metalloproteinase -2 and matix metalloproteinase -9 levels were determined by ELISA at the time of intensive care unit admission. Results: Severe traumatic brain injury was associated with a 46% intensive care unit mortality rate. Higher plasma matrix metalloproteinase -9 concentrations were associated with mortality: 147.94 ± 18.00ng/mL for survivors and 224.23 ± 23.86ng/mL for nonsurvivors (mean ± standard error of the mean, p = 0.022). In contrast, there was no significant association between matrix metalloproteinase -2 levels and intensive care unit mortality: 315.68 ± 22.90ng/mL for survivors and 336.55 ± 24.29ng/mL for nonsurvivors (p = 0.499). Additionally, there were no significant associations between matrix metalloproteinase -2 (p = 0.711) and matrix metalloproteinase -9 (p = 0.092) levels and the presence of associated lesions. Conclusion: Increased plasma matrix metalloproteinase -9 levels were associated with intensive care unit mortality following severe traumatic brain injury, regardless of the presence of extracerebral injuries. Conversely, in this same context, plasma matrix metalloproteinase -2 levels were not associated with short-term fatal outcome prediction.

Pain catastrophizing is associated with the Val66Met polymorphism of the brain-derived neurotrophic factor in fibromyalgia

Abstract Background: Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome that impacts negatively patient's daily lives. Its pathogenesis is characterized by a complex relationship between biological and psychosocial factors not fully understood yet. Pain catastrophizing is associated with FM and is an important predictor of outcomes. This study aimed to answer two questions: (i) whether the allele and genotype frequencies of BDNF Val66Met (rs6265) polymorphism differs between FM patients and healthy controls (HC); and (ii) if the BDNF Val66Met polymorphism is a factor that predicts pain catastrophizing in FM. Methods: In a cross-sectional design, 108 FM patients and 108 HC were included. FM patients responded to the Brazilian Portuguese version of the Pain Catastrophizing Scale (BP-PCS) to assess pain catastrophizing, as well as other validated tools for anxiety (The State-Trait Anxiety Inventory - STAI), depression (Beck Depression Inventory II -BDI-II) and functional aspects (Fibromyalgia Impact Questionnaire - FIQ; Central Sensitization Inventory validated and adapted for Brazilian population - CSI-BP; Pittsburgh Sleep Quality Index - PSQI; and Resilience Scale). All subjects were genotyped for the BDNF Val66Met polymorphism. Results: Val allele was significantly more frequent in FM patients compared to the control group (p < 0.05). Also, FM patients with Val/Val genotype showed more pain catastrophizing thoughts, and this genotype was significantly associated with magnification and rumination dimensions of BP-PCS (p < 0.05). Furthermore, there were significant differences in levels of anxiety and symptoms of depression, years of education, and the functional situation between the FM and control groups. Conclusions: The findings show an association of BDNF Val66Met polymorphism with pain catastrophizing in FM, which opens new avenues to comprehend the interplay between molecular genetic characteristics and neuroplasticity mechanisms underpinning FM.(AU)

Associações entre polimorfismos genéticos da álcool: desidrogenase e o transtorno por uso de álcool / Associations between genetic polymorphisms of alcohol: dehydrogenase and alcohol use disorder

O transtorno por uso de álcool (TUA) é influenciado pela genética, principalmente na metabolização do etanol. Os genes da álcool desidrogenase (ADH1B/ADH1C), enzima que transforma o etanol, apresentam SNPs (single nucleotide polymorphisms) que resultam em isoenzimas com diferentes taxas catalíticas. Estudos demonstraram que os SNPs Arg48His, Arg370Cys, Arg272Gln e Ile350Val contribuem para o TUA. Este artigo revisou os estudos que investigaram SNPs em ADH1B (Arg48His/Arg370Cys) e ADH1C (Arg272Gln/Ile350Val), bem como avaliou as variações nas frequências alélicas desses genes e a influência no TUA nas diferentes populações no mundo. As frequências alélicas dos polimorfismos foram comparadas pelos testes qui-quadrado de Pearson e exato de Fisher (p < 0,05). O SNP Arg48His confere proteção para o TUA em euroamericanos, latino-americanos, europeus, brasileiros, asiáticos e australianos. O SNP Arg370Cys confere proteção para o TUA em afrodescendentes. Os SNPs Arg272Gln e Ile350Val predispõem o TUA principalmente em europeus. Os SNPs Arg48His, Arg370Cys e Arg272Gln/Ile350Val foram mais frequentes em amostras de leste-asiáticos (69,7%), africanos (19,1%) e europeus (40,5%), respectivamente (p < 0,01). Os diferentes alelos dos genes ADH1B/ADH1C devido a SNPs têm uma importante contribuição no TUA. As frequências desses alelos variam conforme a população, resultando em diferentes efeitos no TUA. (AU)

Alcohol use disorder (AUD) is influenced by genetics, especially in the metabolism of ethanol. The ethanol dehydrogenase genes (ADH1B/ADH1C), which convert ethanol, have single nucleotide polymorphisms (SNPs) that result in isoenzymes with different catalytic rates. Studies have shown that the Arg48His, Arg370Cys, Arg272Gln, and Ile350Val SNPs contribute to AUD. This article reviewed the studies that investigated SNPs in ADH1B (Arg48His/Arg370Cys) and ADH1C (Arg272Gln/Ile350Val) and evaluated variations in the allele frequencies of these genes and their influence on AUD in different populations worldwide. The allele frequencies of the polymorphisms were compared by Pearson's chi-square and Fisher's exact tests (p < 0.05). The Arg48His SNP provides protection against AUD in Euro-Americans, Latin Americans, Europeans, Brazilians, Asians, and Australians. The Arg370Cys SNP provides protection against AUD in Afro-descendants. The Arg272Gln and Ile350Val SNPs predispose to AUD mainly in Europeans. The Arg48His, Arg370Cys, and Arg272Gln/Ile350Val SNPs were more frequent in East Asians (69.7%), Africans (19.1%), and Europeans (40.5%), respectively (p < 0.01). The different alleles of the ADH1B/ADH1C genes due to SNPs make an important contribution to AUD. The frequencies of these alleles vary among different populations, resulting in different effects on AUD..(AU)

Increasing prevalence and dissemination of invasive nontyphoidal Salmonella serotype Typhimurium with multidrug resistance in hospitalized patients from southern Brazil

ABSTRACT Introduction: Nontyphoidal Salmonella serotypes are the main cause of human food-borne infection, including several hospitalization cases in the developing countries. Aim: To detect the main serotypes and to characterize the antibiotic resistance of human non-enteric and enteric nontyphoidal Salmonella from clinical isolates in Brazil. Methods: Salmonella serotypes were identified by microbiological and molecular methods. Susceptibility testing to antibiotics was performed by agar disk diffusion. Real-time PCRs were carried out for the detection of the genus Salmonella as well as serotypes Typhimurium and Enteritidis. Results: A total of 307 nontyphoidal Salmonella were isolated from 289 different patients in a reference laboratory (LACEN-RS) from Southern Brazil in a six-year period (2010-2015). There were 45 isolates from emerging cases and 244 from sporadic cases in hospitalized patients. Non-enteric isolates were detected in 42.6% of the patients from sources such as urine, blood and other clinical fluids. Serological and PCR-specific tests demonstrated that Typhimurium (48.4%) and Enteritidis (18.3%) were the most frequent serotypes. Typhimurium isolates were generally resistant to three or more antibiotic classes, while Enteritidis isolates to one or two classes. Typhimurium was the most frequent serotype in all samples (48.4%), mainly among the hospitalized patients (55.6%), and presented the highest rates of multidrug resistance (59.3% of the isolates of this serotype). Further, the prevalence of this serotype increased along the years of the study in comparison to other nontyphoidal Salmonella serotypes. Conclusion: Greater public health attention should be given to prevent salmonellosis in the community and in hospital settings to reduce the rates of Typhimurium strains with multidrug resistance.

Helicobacter pylori eradication: influence of interleukin-1beta -31 C/T polymorphism

ABSTRACT Aim To analyze the influence of the -31 C/T polymorphism of the interleukin-1β gene on Helicobacter pylori eradication therapy success in patients with functional dyspepsia. Methods Functional dyspepsia was diagnosed according to the Rome III criteria. All patients underwent upper gastrointestinal endoscopy, and gastric biopsies were obtained at screening and 12 months after randomization (last follow-up visit). Urease test and histological examination were performed to define the H. pylori status. Patients received twice-daily amoxicillin, clarithromycin and omeprazole for 10 days. Genotyping of the interleukin-1beta -31 C/T polymorphism (rs1143627) was performed using polymerase chain reaction-restriction fragment length polymorphism. Results One hundred forty-nine patients received treatment with triple therapy for H. pylori eradication. Only one patient was lost to follow-up, and adherence to study medication was 94.6%. A total of 148 patients (mean age 46.08 ± 12.24 years; 81.8% women) were evaluated for the influence of the interleukin-1beta -31 C/T polymorphism on the outcome of H. pylori eradication therapy. After treatment, bacteria were eradicated in 87% of patients (129/148). Genotype frequencies of the polymorphism were as follows: CC, 38/148 (25.7%); CT, 71/148 (47.9%); and TT, 39/148 (26.4%). Successful eradication rate was 78.9%, 94.4% and 82.1% for the CC, CT and TT genotypes, respectively. The CT genotype was significantly associated with successful H. pylori eradication (p= 0.039). Conclusion This study suggests that the CT genotype of the interleukin-1beta -31 C/T polymorphism plays a role in the successful eradication of H. pylori among patients with functional dyspepsia.

HBV epidemiology and genetic diversity in an area of high prevalence of hepatitis B in southern Brazil

ABSTRACT Background Hepatitis B virus (HBV) infection is a major public health problem in Brazil. HBV endemicity is usually moderate to low according to geographic regions, and high prevalence of this virus has been reported in people of some specific Brazilian counties, including those with a strong influence of Italian colonization in southern Brazil. Analysis of HBV diversity and identification of the main risk factors to HBV infection are necessary to understand hepatitis B epidemiology in these high prevalence regions in southern Brazil. Objective To investigate epidemiological characteristics and HBV genotypes and subgenotypes circulating in a specific city with high HBV prevalence. Methods A cross-sectional study was performed with 102 HBV chronically infected individuals, recruited in reference outpatient clinics for viral hepatitis in a city of high HBV prevalence (Bento Gonçalves) in Rio Grande do Sul state, Brazil between July and December 2010. Socio-demographic, clinical and behavior-related variables were collected in a structured questionnaire. HBV serological markers (HBsAg, anti-HBc), viral load, genotypes/subgenotypes and drug resistance were evaluated and comparatively analyzed among all patients. Results The HBV infected subjects had a mean age of 44.9 (±12.2) years, with 86 patients (84.3%) reporting to have a family history of HBV infection, 51 (50.0%) to share personal objects, and were predominantly of Italian descendants (61; 64.9%). There was a predominance of genotype D (49/54; 90.7%), but genotype A was also detected (5/54; 9.3%). Subgenotypes D1 (1; 4.7%), D2 (3; 14.3%), and D3 (17; 81.0%) were identified. LAM-resistant mutation (rtM204I) and ADV-resistant mutations (rtA181V) were detected in only one patient each. Conclusions These results demonstrate a pivotal role of intrafamilial transmission for HBV spreading in this population. Furthermore, there is a high prevalence of HBV genotype D in this region.

The association between adult-type hypolactasia and symptoms of functional dyspepsia

Abstract Functional dyspepsia and lactose intolerance (adult-type hypolactasia, ATH) are common conditions that may coexist or even be confounded. Their clinical presentation can be similar, however, lactose intolerance does not form part of the diagnostic investigation of functional dyspepsia. Studies on the association between functional dyspepsia and ATH are scarce. This study aimed to evaluate whether ATH is associated with symptoms of functional dyspepsia. Patients fulfilling the Rome III diagnostic criteria for functional dyspepsia underwent genetic testing for ATH. Dyspeptic symptoms were evaluated and scored according to a validated questionnaire. The diagnostic criteria for ATH was a CC genotype for the -13910C/T polymorphism, located upstream of the lactase gene. The mean scores for dyspeptic symptoms were compared between patients with ATH and those with lactase persistence. A total of 197 functional dyspeptic patients were included in the study. Mean age was 47.7 years and 82.7% patients were women. Eighty-eight patients (44.7%) had a diagnosis of ATH. Abdominal bloating scores were higher in ATH patients compared to the lactase persistent patients (P=0.014). The remaining dyspeptic symptom scores were not significantly different between the two groups. The study results demonstrate an association between ATH and bloating in patients with functional dyspepsia.

Risk factors for hepatitis B transmission in South Brazil

BACKGROUND Hepatitis B virus (HBV) infection is a major public health problem in Brazil. Several risk factors are involved in HBV infection and their identification by a rational and essential approach is required to prevent the transmission of this infection in Brazil. OBJECTIVES To evaluate risk factors associated with HBV infection in South Brazil. METHODS A total of 260 patients with HBV and 260 controls from Caxias do Sul (state of Rio Grande do Sul, Brazil) participated in this study. All participants were given a standard questionnaire to yield the sociodemographic information and to identify HBV risk factors. HBV infection was detected by HBsAg test in all participants. FINDINGS HBV infection in these cases was strongly associated with history of a family member HBV-infected, mainly mother [odds ratio (OR) = 4.86; 95% confidence intervals (CI): 1.69-13.91], father (OR = 5.28; 95% CI: 1.58-17.71), and/or siblings (OR = 22.16; 95% CI: 9.39-52.25); sharing personal objects (OR = 1.40; 95% CI: 1.37-2.38); and having history of blood transfusion (OR = 2.05; 95% CI: 1.10-2.84). CONCLUSIONS HBV infection was strongly associated with having a family member infected with hepatitis B, sharing personal objects, and having history of blood transfusion.

Cervical human papillomavirus infection and persistence: a clinic-based study in the countryside from South Brazil

Abstract Human papillomavirus (HPV) infection is common in sexually active women and viral persistence may cause intraepithelial lesions and eventually progress to cervical cancer (CC). The present study aimed to investigate epidemiological factors related to HPV infection and to evaluate viral persistence and CC precursor lesions frequencies in women from a city in the countryside of South Brazil. Three hundred women were recruited from a primary public health care clinic. The patients were interviewed and underwent sampling with cervical brushes for HPV-DNA detection/typing by a PCR-based assay and cytological analysis by Pap smear test. HPV was detected in 47 (15.7%) women. HPV infection was significantly associated with young age (<30 years) and low socio-economic status. Seventeen (5.7%) women presented cytological abnormalities, three of them with precursor CC intraepithelial lesions. A subgroup of 79 women had been previously analyzed and thirteen (16.4%) were persistently infected, two with precursor CC intraepithelial lesions and high-risk HPV types infection (both of them without cervical abnormalities in the first exam). In conclusion, HPV infection was associated with young age (<30 years) and low family income; viral persistence was low (16.4%) but related to CC precursor lesions; and HPV-DNA high risk types detection would help to screen CC in the population.

Frequencies of polymorphisms of the Rh, Kell, Kidd, Duffy and Diego systems of Santa Catarina, Southern Brazil

Background Red blood cell genes are highly polymorphic with the distribution of alleles varying between different populations and ethnic groups. The objective of this study was to investigate gene polymorphisms of blood groups in the state of Santa Catarina, Southern Brazil. Methods Three hundred and seventy-three unrelated blood donors and 31 transfusion-dependent patients were evaluated to investigate polymorphisms of the Rh, Kell, Duffy, Kidd, and Diego blood group systems in a population from the state of Santa Catarina. The subjects, from seven regions that comprise the blood-banking network of the state, were assessed between August 2011 and March 2014. The genotypes of the Rh, Kell, Duffy, Kidd, and Diego systems were determined using the restriction fragment length polymorphism-polymerase chain reaction and allele-specific polymerase chain reaction techniques. Results The genotype frequencies in this study were significantly different when populations from different regions of Santa Catarina were compared. Furthermore, there were also significant differences in the genetic frequencies compared to other Brazilian states. The genotype frequencies of the Kell and Kidd blood groups are similar to European populations from Naples, Italy and Zurich, Switzerland. Conclusion This article reports for the first time the frequency of polymorphisms of blood group systems in blood donors from Santa Catarina, Southern Brazil.

HIV-1 epidemiology and circulating subtypes in the countryside of South Brazil

INTRODUCTION: Human immunodeficiency virus type 1 (HIV-1) has spread worldwide, with several subtypes and circulating recombinant forms. Brazil has an incidence of 20.5 HIV-1/acquired immunodeficiency syndrome (AIDS) patients per 100,000 inhabitants; however, the Southernmost State of Rio Grande do Sul (RS) has more than twice the number of HIV-1-infected people (41.3/100,000 inhabitants) and a different pattern of subtype frequencies, as previously reported in studies conducted in the capital (Porto Alegre) and its metropolitan region. This study examined HIV-1/AIDS epidemiological and molecular aspects in the countryside of Rio Grande do Sul. METHODS: Socio-demographic, clinical and risk behavioral characteristics were obtained from HIV-1-positive adult patients using a structured questionnaire. HIV-1 subtypes were determined by nested-polymerase chain reaction (PCR) and sequencing of the pol and env genes. RESULTS: The study sample included 149 (55% women) patients with a mean age of 41.8 ± 11.9 years. Most (73.8%) patients had a low education level and reported heterosexual practices as the most (91.9%) probable transmission route. HIV-1 subtypes were detected in 26 patients: 18 (69.2%) infected with subtype C, six (23.1%) infected with subtype B and two (7.7%) infected with BC recombinant forms. CONCLUSIONS: These data highlight the increasing number of HIV-1 subtype C infections in the countryside of South Brazil. .

Valor prognóstico dos níveis de DNA circulante em pacientes graves e em pacientes com trauma / Prognostic value of circulating DNA levels in critically ill and trauma patients

Nos últimos anos, o número de estudos que investigam os ácidos nucleicos circulantes como potenciais biomarcadores tem aumentado. A detecção desses biomarcadores é uma alternativa minimamente invasiva para o diagnóstico e o prognóstico de diversas condições clínicas. O valor dos níveis de DNA circulante como biomarcador preditivo foi demonstrado em pacientes com numerosas patologias agudas que apresentam riscos elevados de necessitar cuidados intensivos e de sofrer mortalidade hospitalar. Os mecanismos pelos quais os níveis de DNA circulante aumentam em pacientes com essas condições ainda são obscuros. Nesta revisão, focalizamos o potencial uso deste biomarcador para predição prognóstica em pacientes graves e pacientes com trauma. A revisão da literatura foi feita por meio de busca no MedLine utilizando o PubMed em inglês.

The number of studies investigating circulating nucleic acids as potential biomarkers has increased in recent years. The detection of such biomarkers is a minimally invasive alternative for the diagnosis and prognosis of various clinical conditions. The value of circulating DNA levels as a predictive biomarker has been demonstrated in patients suffering from numerous acute pathologies that have a high risk of intensive care needs and in-hospital deaths. The mechanism by which circulating DNA levels increase in patients with these conditions remains unclear. In this review, we focused on the potential use of this biomarker for prognosis prediction in critically ill and trauma patients. The literature review was performed by searching MedLine using PubMed in the English language.

A complete molecular biology assay for hepatitis C virus detection, quantification and genotyping

Introduction Molecular biology procedures to detect, genotype and quantify hepatitis C virus (HCV) RNA in clinical samples have been extensively described. Routine commercial methods for each specific purpose (detection, quantification and genotyping) are also available, all of which are typically based on polymerase chain reaction (PCR) targeting the HCV 5′ untranslated region (5′UTR). This study was performed to develop and validate a complete serial laboratory assay that combines real-time nested reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) techniques for the complete molecular analysis of HCV (detection, genotyping and viral load) in clinical samples. Methods Published HCV sequences were compared to select specific primers, probe and restriction enzyme sites. An original real-time nested RT-PCR-RFLP assay was then developed and validated to detect, genotype and quantify HCV in plasma samples. Results The real-time nested RT-PCR data were linear and reproducible for HCV analysis in clinical samples. High correlations (> 0.97) were observed between samples with different viral loads and the corresponding read cycle (Ct - Cycle threshold), and this part of the assay had a wide dynamic range of analysis. Additionally, HCV genotypes 1, 2 and 3 were successfully distinguished using the RFLP method. Conclusions A complete serial molecular assay was developed and validated for HCV detection, quantification and genotyping. .

Análise molecular da hipolactasia primária do tipo adulto: uma nova visão do diagnóstico de um problema antigo e frequente / Molecular analysis of adult-type hypolactasia: a new view into the diagnosis of an old frequent condition

A intolerância ao leite de vaca e seus derivados acomete grande parte da população mundial. No Brasil, também se observa elevada prevalência dessa condição. A principal causa de intolerância à lactose é a Hipolactasia Primária do Tipo Adulto (HPTA), uma condi- ção determinada geneticamente e que se caracteriza pela redução da atividade da enzima lactase a partir dos primeiros anos de vida. As bases genéticas da HPTA estão relacionadas à identificação de polimorfismos de nucleotídeo único na região promotora do gene LCT (que codifica a lactase). Conforme o genótipo, haverá persistência ou não da atividade desta enzima na idade adulta. No presente artigo, são abordados aspectos clínicos e diagnósticos desta frequente condição, à luz dos conhecimentos atuais de suas bases genético-moleculares. Os autores ressaltam a importância da análise molecular da HPTA na estratégia atual de investigação diagnóstica frente a sintomas de intolerância à lactose (AU)

Intolerance to cow's milk and its derivatives affects a great part of the world's population. In Brazil, there is also a high prevalence of this condition. The main cause of lactose intolerance is primary hypolactasia (or adult-type hypolactasia ­ ATH)), a genetically determined condition characterized by reduction of lactase activity from the first years of life. The genetic basis of ATH is related to the identification of single nucleotide polymorphisms in the promoter region of the LCT gene (encoding lactase). Depending on genotype, the activity of this enzyme will persist or not into adulthood. In this article, clinical and diagnostic aspects of this condition are discussed in light of current knowledge of its molecular genetic bases. The authors emphasize the importance of molecular analysis of ATH in the current strategy of diagnostic investigation upon symptoms of lactose intolerance (AU)

Identificação de genes envolvidos na síntese de proteínas de células musculares lisas com expressão aumentada em placas ateromatosas associados a hiperplasia neointimal após implante de stents não-farmacológicos: estudo GENESIS-R / Identification of genes involved in smooth muscle cell protein synthesis with increased expression in atheromathous plaques associated to neointim al hyperplasia after bare-metal stenting: GENESISI-R Study

Introdução: A reestenose coronária é um fenômeno pouco compreendidoe que permanece como um desafio mesmo na era dos stents farmacológicos. Este estudo tem como objetivo identificar genes envolvidos na síntese de proteínas estruturais e funcionais de células musculares lisas com expressão aumentada em placas ateromatosas de humanos associadosa hiperplasia neointimal após o implante de stents não-farmacológicos. Métodos: Placas ateromatosas foram obtidasmediante aterectomia direcionada, previamente ao implante do stent. A análise da expressão dos genes foi realizada utilizando-se o sistema Affymetrix GeneChip. Os pacientes foramsubmetidos a ultrassom intracoronário 6 meses após o procedimento para análise volumétrica intrastent. Foi avaliada a correlação entre a expressão gênica de placas ateromatosas e o porcentual de hiperplasia intimal intrastent. Resultados: A maioria dos pacientes era do sexo masculino (85,7%), com60,2 ± 11,4 anos de idade, 35,7% eram diabéticos e o porcentual de hiperplasia intimal intrastent foi de 29,9 ± 18,7%.Não houve variação do porcentual de hiperplasia intimal intrastent entre os pacientes com ou sem diabetes (29,5% vs. 30,7%; P = 0,89). Não houve correlação entre a extensão do stent e o porcentual de hiperplasia intimal intrastent (r = -0,26; P = 0,26) ou entre o diâmetro do stent e o porcentual dehiperplasia intimal intrastent (r = 0,14; P = 0,56). Oito genes envolvidos na síntese de proteínas estruturais e funcionais de células musculares lisas apresentaram correlação positiva como porcentual de hiperplasia intimal intrastent. Conclusões: As lesões coronárias de novo apresentam expressão aumentada de genes relacionados com a síntese de proteínas estruturais e funcionais de células musculares lisas associados a futurahiperplasia neointimal intrastent significativa, surgindo como novos alvos terapêuticos.

Prevalência de subtipos do HIV-1 em amostra de pacientes de um centro urbano no sul do Brasil / Prevalence of HIV-1 subtypes in patients of an urban center in Southern Brazil / Prevalencia de subtipos de VIH-1 en muestra de pacientes de un centro urbano en el sur de Brasil

OBJETIVO: Estimar a prevalência dos subtipos do HIV-1 e analisar fatores associados. MÉTODOS: Foi realizado um estudo transversal com amostra de conveniência de 80 pacientes adultos HIV-positivos atendidos em serviço especializado em DST/Aids em Canoas, RS, no período de julho de 2008 a janeiro de 2009. A determinação dos subtipos do HIV foi realizada por amplificação de fragmento do genoma viral pela reação em cadeia da polimerase seguida do seqüenciamento dos fragmentos amplificados. Variáveis sociodemográficas, clínicas e comportamentais foram coletadas em questionário estruturado. Foi realizada análise estatística univariada utilizando os testes de qui-quadrado e t de Student. RESULTADOS: Foi observada uma prevalência maior do subtipo C (43,8 por cento; IC 95 por cento: 32,9;54,6), seguida pelo CRF31_BC (35,0 por cento; IC 95 por cento: 24,6;45,5) e subtipos B (18,8 por cento; IC 95 por cento: 10,2;27,3) e F (2,4 por cento; IC 95 por cento: 0;5,9). Outros subtipos de HIV-1 não foram observados. Pacientes infectados com CRF31_BC apresentaram diagnóstico mais recente do que os pacientes infectados com o subtipo B (p < 0,05). Observou-se também maior freqüência de co-infecção com outros vírus (hepatites B e C e T-linfotrópicos humanos) nos indivíduos portadores do CRF31_BC do que nos demais subtipos. Com relação aos aspectos sociodemográficos, não foram observadas diferenças na distribuição dos subtipos e formas recombinantes quanto ao sexo e práticas sexuais. CONCLUSÕES: Os resultados obtidos indicam uma freqüência maior do subtipo C e do CRF31_BC nesse centro urbano do sul do Brasil, com possíveis vias de transmissão diferentes.

OBJECTIVE: To estimate the prevalence of HIV-1 subtypes and analyze factors associated. METHODS: A cross-sectional study was performed with a convenience sample of 80 adult HIV-positive patients, users of an AIDS/STD specialized service, in the city of Canoas, Southern Brazil, between July 2008 and January 2009. Determination of HIV subtypes was performed with the amplification of viral genome fragment, using polymerase chain reaction, followed by sequencing of the amplified fragments. Sociodemographic, clinical and behavioral variables were collected in a structured questionnaire. Univariate statistical analysis was performed, using chi-square test and Student's t-test. RESULTS: A higher prevalence of subtype C was found (43.8%; 95% CI: 32.9;54.6), followed by CRF31_BC (35.0%; 95% CI: 24.6;45.5) and subtypes B (18.8%; 95% CI: 10.2;27.3) and F (2.4%; 95% CI: 0;5.9). Other HIV-1 subtypes were not observed. Patients infected with CRF31_BC were diagnosed more recently than patients infected with subtype B (p<0.05). In addition, there was a higher frequency of co-infection with other viruses (hepatitis B and C and human T-lymphotropic viruses) in individuals with CRF31_BC, compared to other subtypes. With regard to sociodemographic aspects, there were no differences in the distribution of subtypes and recombinant forms, in terms of gender and sexual practices. CONCLUSIONS: Results obtained indicate a higher frequency of subtype C and CRF31_BC in this urban center of Southern Brazil, with possible different ways of transmission.

OBJETIVO: Estimar la prevalencia de los subtipos de VIH-1 y analizar factores asociados. MÉTODOS: Se realizó un estudio transversal con muestra de conveniencia de 80 pacientes adultos VIH-positivos atendidos en servicio especializado en DST/Sida en Canoas, Sur de Brasil, en el período de julio de 2008 a enero de 2009. La determinación de los subtipos de VIH fue realizada por amplificación de fragmento del genoma viral por la reacción en cadena de la polimerasa seguida de la secuenciación de los fragmentos amplificados. Variables sociodemográficas, clínicas y conductuales fueron colectadas en cuestionario estructurado. Se realizó análisis estadístico univariado utilizando las pruebas de chi-cuadrado y t de Student. RESULTADOS: Se observó una prevalencia mayor del subtipo C (43,8%; IC 95%:32,9;54,6), seguido de la CRF31_BC (35,0%; IC 95%: 24,6;45,5) y subtipos B (18,8%; IC 95%: 10,2;27,3) y F (2,4%; IC 95%: 0;5,9). Otros subtipos de VIH-1 no fueron observados. Pacientes infectados con CRF31_BC presentaron diagnóstico más reciente que los pacientes infectados con el subtipo B (p<0,05). Se observó también una mayor frecuencia de co-infección con otros virus (hepatitis B y C y T-linfotrópicos humanos) en los individuos portadores del CRF31_BC en comparación con los demás subtipos. Con relación a los aspectos sociodemográficos, no fueron observadas diferencias en la distribución de los subtipos y formas recombinantes con relación al sexo y prácticas sexuales. CONCLUSIONES: Los datos obtenidos en el presente estudio indican una mayor frecuencia del subtipo C y de la CRF31_BC en este centro urbano del sur de Brasil y sugieren que dichos subtipos pueden presentar vías de transmisión diferentes.

Ausência de associação entre polimorfismo do gene da interleucina-1 beta e o prognóstico de pacientes com traumatismo crânio-encefálico grave / Lack of association between interleukin-1 gene polymorphism and prognosis in severe traumatic brain injury patients

OBJETIVO: O traumatismo crânio-encefálico é a principal causa de óbito em indivíduos com idade entre 1 a 45 anos. O desfecho do traumatismo crânio-encefálico pode estar relacionado, além de fatores pré-morbidade e gravidade do dano, com fatores genéticos. Genes que podem ter relação com o resultado pós-trauma vêm sendo estudados, porém, ainda existem poucas informações sobre a associação entre polimorfismos genéticos e o desfecho do traumatismo crânio-encefálico. O gene da interleucina-1 beta (IL-1B) é um dos genes estudados, pois esta citocina encontra-se em níveis elevados após o traumatismo crânio-encefálico e pode afetar de forma negativa seu desfecho. O objetivo do presente estudo foi analisar o polimorfismo -31C/T, localizado na região promotora do gene IL-1B, em pacientes com traumatismo crânio-encefálico grave visando correlacioná-lo com o desfecho primário precoce (alta do centro de terapia intensiva ou morte). MÉTODOS: Foram estudados 69 pacientes internados por traumatismo crânio-encefálico grave em três hospitais de Porto Alegre e região metropolitana. O polimorfismo foi analisado através da reação em cadeia da polimerase, seguida da digestão com enzima de restrição. RESULTADOS: O traumatismo crânio-encefálico grave foi associado a uma mortalidade de 45 por cento. Não foram observadas diferenças significativas nas frequências alélicas e genotípicas entre os grupos de pacientes divididos pelo desfecho do traumatismo crânio-encefálico. CONCLUSÃO: Nossos resultados sugerem que o polimorfismo -31C/T do gene IL-1B não tem impacto significativo no desfecho fatal dos pacientes com traumatismo crânio-encefálico grave.

OBJECTIVE: Traumatic brain injury is the major cause of death among individuals between 1-45 years-old. The outcome of traumatic brain injury may be related to brain susceptibility to the injury and genetic factors. Genes that may affect traumatic brain injury outcome are being investigated, however there is still few data concerning the association between genetic polymorphisms and traumatic brain injury outcome. The interleukin-1 beta gene (IL-1B) is one of the most studied genes, because levels of this cytokine are raised after traumatic brain injury and this can affect worsen the prognosis. The aim of this study was to test whether the -31C/T polymorphism, located at the promoter region of the IL-1B gene, is associated with primary short-term outcome (death or intensive care unit discharge) in severe traumatic brain injury patients. METHODS: Were studied 69 patients admitted with severe traumatic brain injury in three hospitals of the metropolitan region of Porto Alegre. The polymorphism was analyzed by polymerase chain reaction, followed by restriction digestion. RESULTS: Severe traumatic brain injury was associated with a 45 percent mortality rate. No significant differences were observed in the allele and genotype frequencies between patients stratified by traumatic brain injury outcome. CONCLUSION: Our findings suggest that -31C/T IL-1B gene polymorphism have no significant impact on the outcome of patients after acute severe traumatic brain injury.