FOXP3 variants are independently associated with transforming growth factor Β1 plasma levels in female patients with inflammatory bowel disease

Objective: The aim of this study was to evaluate the association of -924 G>A (rs2232365) and -3279 C>A (rs3761548) FOXP3 variants with IBD susceptibility, clinical and endoscopic activity, and IL-10 and TGF-β1 plasma levels. Method: The study included 110 IBD female patients, 60 with Ulcerative Colitis (UC) and 50 with Crohn's Disease (CD), and 154 female controls. FOXP3 variants were determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Plasma levels of IL-10 and TGF-β1 were determined using immunofluorimetric assay. Results: AA genotype of rs2232365 and rs3761548 was associated with CD (OR = 3.147, 95% CI 1.015–9.758, p = 0.047) and UC (OR = 3.221, 95% CI 1.050–9.876, p = 0.041) susceptibility, respectively. However, were not associated with TGF-β1 and IL-10 levels, and endoscopic/clinical activity disease. GAGA haplotype was associated with IBD (OR = 4.003, 95% CI 1.100–14.56, p = 0.035) and UC susceptibility (OR = 6.107, 95% CI 1.609–23.18, p = 0.008). In addition, IBD patients with the GAGA haplotype had lower TGF-β1 levels (p = 0.041). Moreover, G/C haplotype (dominant model) had a protective effect of 60% in CD susceptibility and lower Endoscopic Severity Index. Conclusions: These results suggest that FOXP3 variants could exert a role in the Treg, which could be one of the factors involved in the susceptibility and pathogenesis of IBD

Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná , Brazil Soroprevalência da infecção pelo virus da hepatite E (VHE) em candidatos a doadores de sangue voluntários do Hemocentro Regional de Londrina, Londrina, Estado do Paraná, Brasil

A cross-sectional study was carried out among 996 volunteer blood donors enrolled from May 1999 to December 1999 to determine the seroprevalence of hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná, Brazil, and to evaluate whether the rate of seroprevalence of IgG anti-HEV antibodies is associated with sociodemographic variables and with seropositivity for hepatitis A virus (HAV) infection. All participants answered the questionnaire regarding the sociodemographic characterisitcs. Serum samples were tested for IgG antibodies to HEV (anti-HEV) by an enzyme linked immunoassay (ELISA). All serum samples positive for anti-HEV IgG and 237 serum samples negative for anti-HEV were also assayed for IgG anti-HAV antibodies by ELISA. Anti-HEV IgG was confirmed in 23/996 samples, resulting in a seroprevalence of 2.3% for HEV infection, similar to previous results obtained in developed countries. No significant association was found between the presence of anti-HEV IgG antibodies and the sociodemographic variables including gender, age, educational level, rural or urban areas, source of water, and sewer system (p > 0.05). Also, no association with seropositivity for anti-HAV IgG antibodies was observed (p > 0.05). Although this study revealed a low seroprevalence of HEV infection in the population evaluated, the results showed that this virus is circulating among the population from Londrina, South Brazil, and point out the need of further studies to define the clinical and epidemiological importance of HEV infection and to identify additional risk factors involved in the epidemiology and pathogenesis of this infection in this population.<br>Os objetivos do estudo foram determinar a soroprevalência da infecção pelo vírus da hepatite E (VHE) em candidatos a doadores de sangue voluntários do Hemocentro Regional de Londrina, Paraná, e avaliar se essa soroprevalência está associada com variáveis socio-demográficas e com o índice de soropositividade para hepatite por vírus A (VHA). Foi realizado estudo transversal para determinar a taxa de soroprevalência da infecção pelo VHE em 996 candidatos a doadores de sangue. Todos os participantes responderam um questionário sobre características sociodemográficas. A pesquisa de anticorpos específicos IgG anti-VHE foi realizada por método de enzimaimunoensaio (ELISA). Todas as amostras soropositivas para IgG anti-VHE e 237 amostras soronegativas para IgG anti-VHE foram submetidas também à pesquisa de IgG anti-VHA por ELISA. Entre as 996 amostras de soro analisadas, anticorpos IgG anti-VHE foram detectados em 23 amostras, resultando em uma soroprevalência de 2,3% (IC 95%: 1,5 - 3,5), semelhante aos resultados de estudos realizados em países desenvolvidos. Não houve associação entre o índice de soropositividade de IgG anti-VHE e as variáveis sociodemográficas (sexo, idade, escolaridade, procedência, fonte de água e origem dos dejetos); também não se detectou associação entre soropositividade para IgG anti-VHE com soropositividade para IgG anti-VHA. Os resultados obtidos sugerem que, embora tenha se observado uma baixa prevalência da infecção pelo VHE na população analisada, verificou-se que existe circulação do VHE no município de Londrina e que estudos posteriores são necessários para definir a importância clínica e epidemiológica da infecção pelo VHE nesse município bem como identificar outros possíveis fatores de risco envolvidos na epidemiologia da infecção pelo VHE

Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination