Single nucleotide polymorphisms (SNPs) at -238 and -308 positions in the TNFalpha promoter: clinical and bacteriological evaluation in leprosy.

Tumor necrosis factor alpha (TNFalpha) plays a key role in orchestrating the complex events involved in inflammation and immune response. The presence of single nucleotide polymorphisms (SNPs) within the promoter region of the TNFa gene has been associated with a number of diseases. The aim of this study was to investigate the distribution of polymorphisms at positions -238 (G/A) and -308 (G/A) at the TNFalpha promoter, and its association to the outcome of different clinical forms of leprosy. Furthermore, the bacteriological index (BI) was evaluated among genotyped multibacillary (MB) patients in order to investigate the possible influence of each polymorphism on the bacterial load. This study included a total of 631 leprosy patients being 401 MB and 230 paucibacillary (PB), that was further separated according to its ethnicity (Afro- and Euro-Brazilians). The combination of SNPs in haplotypes generated three different arrangements: TNFG-G, TNFG-A and TNFA-G. In spite of the marked differences observed in the frequency of the haplotypes along the ethnic groups, no statistical differences were observed in haplotype frequencies between MB and PB patients. The BI analyses showed a lower bacteriological index among the -308 carriers, while the BI of the -238 carriers was higher. Although no significance has been achieved in this analysis regarding the influence of the polymorphisms to the development of the clinical outcome, it seems that in a different stage (among the MB patients) the polymorphisms could contribute to the degree of severity observed.

Differential TNFalpha mRNA regulation detected in the epidermis of leprosy patients.

The epidermis is an important site of the immunoinflammatory response in the skin. In the present study, the expression of cytokine and ICAM-1 (intercellular adhesion molecule-1) genes was evaluated by RT-PCR in the epidermis isolated from biopsies from 25 reactional leprosy patients. TNFalpha and IL-6 mRNAs were detected in all individuals during the reactional state (reversal reaction or erythema nodosum leprosum), IL-8 message was detected in 66.6% and 62.5% of the patients, IL-12 mRNA was present in 91.6% and 62.5% and ICAM-1 in 100% and 71.4%, respectively. In addition, when skin biopsies were obtained from the same patients before and during the reactional episode, an enhancement in cytokine mRNA, but not in ICAM-1 mRNA, was observed. Seven patients were also evaluated at the onset of reaction and during antiinflammatory treatment. In contrast to a preferential decrease in the TNFalpha gene detected in the dermis, during the treatment phase, persistent/enhanced TNFalpha mRNA expression was detected in the epidermis in six out of the seven patients assessed. This peculiar pattern of expression might reflect a differential impact that in vivo antiinflammatory therapy has on the epidermis. The present findings indicate that the epidermis plays an important role in the local inflammatory response in leprosy and that the profile of response detected in the epidermis during the reactions may be regulated differently from that in the dermis.

Differential TNFalpha mRNA regulation detected in the epidermis of leprosy patients

The epidermis is an important site of the immunoinflammatory response in the skin. In the present study, the expression of cytokine and ICAM-1 (intercellular adhesion molecule-1) genes was evaluated by RT-PCR in the epidermis isolated from biopsies from 25 reactional leprosy patients. TNFalpha and IL-6 mRNAs were detected in all individuals during the reactional state (reversal reaction or erythema nodosum leprosum), IL-8 message was detected in 66.6 per cent and 62.5 per cent of the patients, IL-12 mRNA was present in 91.6 per cent and 62.5 per cent and ICAM-1 in 100 per cent and 71.4 per cent, respectively. In addition, when skin biopsies were obtained from the same patients before and during the reactional episode, an enhancement in cytokine mRNA, but not in ICAM-1 mRNA, was observed. Seven patients were also evaluated at the onset of reaction and during antiinflammatory treatment. In contrast to a preferential decrease in the TNFalpha gene detected in the dermis, during the treatment phase, persistent/enhanced TNFalpha mRNA expression was detected in the epidermis in six out of the seven patients assessed. This peculiar pattern of expression might reflect a differential impact that in vivo antiinflammatory therapy has on the epidermis. The present findings indicate that the epidermis plays an important role in the local inflammatory response in leprosy and that the profile of response detected in the epidermis during the reactions may be regulated differently from that in the dermis.

Perdas auditivas congênitas e adquiridas na infância / Congenital and Adquired Deafness in Childhood

A deficiência auditiva na infância constitui grave problema médico e social que altera a capacidade de comunicação e aprendizado - e muitas vezes exclui a criança do convívio social. Objetivo: O objetivo deste trabalho é demonstrar a dificuldade de se obter um diagnóstico etiológico preciso, a importância da prevenção da surdez evitável e do diagnóstico precoce da deficiência auditiva na infância. Material e métodos: Esta pesquisa foi realizada no instituto Felipe Smaldone (escola especializada na estimulação e desenvolvimento do deficiente auditivo), em Belém /PA, no período de dezembro de 1996 a fevereiro de 1997. Foram catalogadas aí 150 crianças, na faixa etária de 2 a 13 anos, de ambos os sexos, dando-se importância principalmente às possíveis causas de deficiência auditiva na infância, e se relacionando também o tipo e o grau de deficiência auditiva. Resultados: Nos resultados observouse o predomínio das causas passíveis de prevenção, como a rubéola congênita (32 casos - 22%), meningite (20 casos - 13%) e o uso de drogas ototóxicas (14 casos - 9%). Conclusão: Não se pode deixar de enfatizar o grande número de casos que permaneceram com origem desconhecida devido principalmente a má informação, desconhecimento ou omissão dos pais e familiares no momento do interrogatório, o que demonstra a grande dificuldade em se obter um diagnóstico etiológico preciso, constituindo assim um desfio ao otorrinolaringologista.

The childhood deafness constitutes a serious social medical problem which impairs both communication and learning abilities, reflecting many times on a poor social interaction of the child. Purposes: The purposes of this work are: to demonstrate the difficulty of providing patients with a precise etiologic diagnosis, the importance of preventing the available deafness and that of the early diagnosis for the childhood deafness. Material and method: This research has been developed at Felipe Smaldone Institute (a speciality school to teach children deafness) from Belém /PA, in the period within December 1996 and February 1997. Meanwhile,150 children from both sexes between the ages of 3 and 13 years have been registered, giving importance mainly to the possible causes for the childhood deafness and relating the type and degree of deafness. Results: The result showed predomination of those causes which are available, such as: congenit rubeolla (32 cases 22%), meningitis (20 cases - 13%), and the use of ototoxis drugs (14 cases - 9%). Conclusion: It's important to emphasize the large number of cases whose origins remain unidentified due to lack of information or patents' omission which accounts for the difficulty in obtaining a precise etiological diagnosis and thus still defying otorhynolaringologists.