Combined Application of Antisense Oligomers to Control Transcription Factors of Candida albicans Biofilm Formation.

Antisense oligomers (ASOs) have been little exploited to control determinants of Candida albicans virulence. Biofilm formation is an important virulence factor of C. albicans, that is regulated by a complex network of transcription factors (such as EFG1, BRG1 and ROB1). Thus, the main goal of this work was to project ASOs, based on the 2'-OMethyl chemical modification, to target BRG1 and ROB1 mRNA and to validate its application either alone or in combination with the EFG1 mRNA target, to reduce C. albicans biofilm formation. The ability of ASOs to control gene expression was evaluate by qRT-PCR. The effect on biofilm formation was determined by the total biomass quantification, and simultaneously the carbohydrates and proteins reduction on extracellular matrix. It was verified that all the oligomers were able to reduce the levels of gene expression and the ability of C. albicans to form biofilms. Furthermore, the combined application of the cocktail of ASOs enhances the inhibition of C. albicans biofilm formation, minimizing biofilm thickness by reducing the quantity of matrix content (protein and carbohydrate). So, our work confirms that ASOs are useful tools for research and therapeutic development on the control of Candida species biofilm formation.

Tuberculosis in renal transplants in Rio de Janeiro.

Retrospective analysis of 982 renal transplants over 21 years (1981 to 2002) sought to evaluate the prevalence of tuberculosis (TB). This analysis included 74 patients: 30 with a past TB history, who had INH prophylaxis since the beginning of immunosuppression, and 44 who only became TB infected after receiving transplants. The diagnosis of TB was made by a compatible medical situation with bacteriological/histological confirmation, which when not possible, underwent a therapeutic test occur. The average time for the illness to surge was 3 years. The mortality rate was 34.9% (15/44). Patients with hepatitis C were more affected. Among those who used INH prophylaxis only one contracted TB, showing that the drug displayed a protection rate of 96.6% (29/30).

[The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis]. / Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

Six-month isoniazid-rifampin treatment for pulmonary tuberculosis in children.

One hundred and seventeen children with pulmonary tuberculosis underwent treatment with a 6-month daily regimen of rifampin (15 mg/kg/day) and isoniazid (10 mg/kg/day). The criteria for the diagnosis of pulmonary tuberculosis were (1) clinical symptoms and signs in 93 children (79%), (2) history of direct contact with an adult with tuberculosis in 106 children (91%), (3) tuberculin reaction of 5 mm or more, without previous bacillus Calmette-Guérin (BCG), in 45 children (38%), (4) suggestive radiologic alterations in all patients, and (5) positive bacteriology or histology in four patients (3%). The treatment was completed by 97 children (83%). The mean weight gain during therapy was 2,145 g. There was an excellent clinicoradiologic response to the treatment, and improvement in chest roentgenograms was observed in all patients at the end of therapy. No relapses occurred among the patients followed for an average of 21.4 months. This study indicates that the treatment of primary pulmonary tuberculosis in children with a combination of rifampin and isoniazid daily for 6 months is efficacious and does not result in any relapse.

Concentration of electrolytes in the sweat of malnourished children.

The sweat test was performed by the method of Gibson and Cooke on 36 children with second and third degree malnutrition, aged from 2 months to 4 years. The results were compared with those from 32 healthy, well nourished controls in the same age range. Determinations were made of sodium and chloride concentrations, chloride/sodium ratio, and the sum of the concentrations of the two electrolytes in each sample. The malnourished children were found to have higher sodium and chloride concentrations than the well nourished ones. None of the normal or malnourished children had a sweat chloride value greater than 60 mmol/l; chloride values within a suspicious range (between 40 and 60 mmol/l) were found in two malnourished children. Two well nourished controls and six malnourished children showed suspicious sweat sodium concentrations; in one child with third degree malnutrition the sodium content was greater than 60 mmol/l. In all results in the suspicious range, or greater than 60 mmol/l, the chloride/sodium ratio was less than 1, and the sum of the two electrolytes was below 140 mmol/l. Based on these results, we conclude that malnourished children have raised sweat sodium and chloride concentrations when compared with well nourished children. The electrolyte values for most of them are not in a suspicious range or consistent with a diagnosis of cystic fibrosis. Unlike that found in cystic fibrosis, the sodium/chloride ratio in our subjects was less than 1 and the sum of both electrolytes never exceeded 140 mmol/l.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose / The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis

Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

Estudo retrospectivo de asmáticos crônicos em serviço de pneumologia / Retrospective study of chronic asthmatics in Pneumology Services

Foram analisados, retrospectivamente, dois grupos de asmáticos: grupo A (50 pacientes) e grupo B (17 pacientes) classificados de acordo com a utilizaçäo ou näo de corticóides, por tempo prolongado, durante o controle ambulatorial. Observou-se que os pacientes do grupo B (uso de corticóide) eram os mais gravemente acometidos, de acordo com a avaliaçäo dos seguintes parâmetros: internamentos mais freqüentes, acompanhamento ambulatorial por período mais longo e necessidade de maior número de medicamentos para controle adequado. O número relativamente alto (25 por cento) de pacientes, utilizando corticóide no controle ambulatorial, ressalta a necessidade de procedimentos mais objetivos, como monitorizaçäo de drogas e avaliaçäo periódica da funçäo pulmonar, dentre outros, como forma de diminuir este índice