Uso de vírus adeno-associado: um avanço na terapia gênica

ResumoA terapia gênica utiliza técnicas de engenharia genética para interferir na origem de uma doença. Nesta técnica introduz-se uma sequência de DNA codificante nas células do paciente como tratamento para a correção de um problema recorrente devido a um gene mutado. O uso de vetores virais recombinantes para introduzir o gene correto no indivíduo tem se mostrado bastante desafiador e promissor. Este artigo tem como objetivo apresentar de forma atualizada os conceitos básicos e as perspectivas da terapia gênica para doenças as doenças: fibrose cística, artrite reumatoide, hemofilia e dislipidemia (deficiência da lipoproteína lipase) utilizando o vírus adeno-associado (VAA) como vetor doador do novo gene. Os avanços obtidos no emprego desta técnica, como método de tratamento, podem contribuir largamente para a otimização da terapêutica e, consequentemente, melhorar a qualidade de vida de pacientes portadores de diferentes doenças incuráveis. Neste sentido, os VAA têm se mostrado tecnologicamente versáteis, seguros e efetivos veículos no procedimento. Palavras-chave: terapia gênica, vírus adeno-associado, fibrose cística, artrite reumatóide, hemofilia, LPLD.

Dermatite e paniculite piogranulomatosas causadas por Nocardia nova em um gato

Este relato descreve os achados clínicos, patológicos e microbiológicos de uma infecção incomum por Nocardia nova em um gato. Um gato macho, sem raça definida, de 3 anos de idade, apresentou ferida cutânea exsudativa e ulcerada. Amostras da lesão foram coletadas para histopatologia e bacteriologia. Histologicamente, a lesão consistiu de dermatite e paniculite piogranulomatosas associadas a colônias grandes e irregulares de bactérias filamentosas e ramificadas. O cultivo bacteriológico revelou bacilos filamentosos, gram-positivos, parcialmente ácido resistentes, visualizados pelas colorações de Gram e Kinyoun, respectivamente. A identificação da Nocardia novafoi confirmada pelo sequenciamento 16S rDNA e análise filogenética. Este é o primeiro caso de paniculite e dermatite piogranulomatosas em um gato causado por Nocardia nova registrado no Brasil.This report describes the clinical, pathological and microbiological findings of an uncommon infection in a cat by Nocardia nova. A 3-year-old male domestic short hair cat with an ulcerated and exudative cutaneous wound was presented for clinical examination. Samples were collected for histopathology and bacteriology diagnosis. Microscopically, the lesion was diagnosed as pyogranulomatous dermatitis and panniculitis with large and irregular colonies of branching filamentous bacterium. Skin bacteriological culture showed gram-positive rods and partially acid-fast branching filaments by gram and kinyoun staining, respectively. The identity of Nocardia nova was confirmed by 16S rDNA sequencing and phylogenetic analysis. This is the first case of pyogranulomatous dermatitis and panniculitis in a cat caused byNocardia nova reported in Brazil

Pyogranulomatous dermatitis and panniculitis due to Nocardia nova in a cat

This report describes the clinical, pathological and microbiological findings of an uncommon infection in a cat by Nocardia nova. A 3-year-old male domestic short hair cat with an ulcerated and exudative cutaneous wound was presented for clinical examination. Samples were collected for histopathology and bacteriology diagnosis. Microscopically, the lesion was diagnosed as pyogranulomatous dermatitis and panniculitis with large and irregular colonies of branching filamentous bacterium. Skin bacteriological culture showed gram-positive rods and partially acid-fast branching filaments by gram and kinyoun staining, respectively. The identity of Nocardia nova was confirmed by 16S rDNA sequencing and phylogenetic analysis. This is the first case of pyogranulomatous dermatitis and panniculitis in a cat caused byNocardia nova reported in Brazil

Nocardia nova causing empyema necessitatis afterlung re-transplantation: a case report

Abstract: We report herein a case of thoracic infection due to Nocardia nova following lung re-transplantation performed for emphysema related to alpha-1-antitrypsin deficiency. The infection extended from the lung into the pleural space, thoracic wall, and mediastinum, presenting as pericarditis and empyema necessitatis. Nocardia nova was identified by 16S ribosomal deoxyribonucleic acid (rDNA) sequencing and phylogenetic analysis. According to a literature search of PubMed, LILACS and MEDLINE databases, we describe herein the first case of empyema necessitatis caused by N. nova species in a transplanted patient

Genotypes and Pathogenicity of Cellulitis Isolates Reveal Traits That Modulate APEC Virulence

<div><p>We characterized 144 <i>Escherichia coli</i> isolates from severe cellulitis lesions in broiler chickens from South Brazil. Analysis of susceptibility to 15 antimicrobials revealed frequencies of resistance of less than 30% for most antimicrobials except tetracycline (70%) and sulphonamides (60%). The genotyping of 34 virulence-associated genes revealed that all the isolates harbored virulence factors related to adhesion, iron acquisition and serum resistance, which are characteristic of the avian pathogenic <i>E. coli</i> (APEC) pathotype. ColV plasmid-associated genes (<i>cvi/cva, iroN, iss, iucD, sitD, traT, tsh</i>) were especially frequent among the isolates (from 66.6% to 89.6%). According to the Clermont method of ECOR phylogenetic typing, isolates belonged to group D (47.2%), to group A (27.8%), to group B2 (17.4%) and to group B1 (7.6%); the group B2 isolates contained the highest number of virulence-associated genes. Clonal relationship analysis using the ARDRA method revealed a similarity level of 57% or higher among isolates, but no endemic clone. The virulence of the isolates was confirmed <i>in vivo</i> in one-day-old chicks. Most isolates (72.9%) killed all infected chicks within 7 days, and 65 isolates (38.1%) killed most of them within 24 hours. In order to analyze differences in virulence among the APEC isolates, we created a pathogenicity score by combining the times of death with the clinical symptoms noted. By looking for significant associations between the presence of virulence-associated genes and the pathogenicity score, we found that the presence of genes for invasins <i>ibeA</i> and <i>gimB</i> and for group II capsule <i>KpsMT</i>II increased virulence, while the presence of <i>pic</i> decreased virulence. The fact that <i>ibeA</i>, <i>gimB</i> and <i>KpsMT</i>II are characteristic of neonatal meningitis <i>E. coli</i> (NMEC) suggests that genes of NMEC in APEC increase virulence of strains.</p></div

Antimicrobial susceptibility of cellulitis isolates.

<p>The susceptibility of 144 APEC isolates to 15 antimicrobials was tested individually using disc diffusion tests.</p

Relationship between APEC pathogenicity score (PS) and presence of different genes.

a<p>Genes that occurred in none (<i>afa/dra</i>, <i>cnf1/2)</i> or all (<i>csgA</i>) isolates are not listed.</p>b<p>Exact <i>p</i> values for the Wilcoxon-Mann-Whitney test.</p>*<p><i>p</i>≤0.05.</p

Pathogenicity scores for MG1655 and five cellulitis isolates.

<p>Ten one-day old chicks were infected with each isolate and observed for 7 days as described in the Materials and Methods section. Data points represent the PS for each chick, and horizontal bars represent the median PS for each isolate. Strain MG1655 was included as negative control.</p