RESUMO

Ganciclovir (GCV) is the first therapeutic choice for prevention and treatment of active cytomegalovirus (CMV) infection in solid organ transplant recipients in Bahia state, Brazil. Prolonged and repeated GCV therapy may result in drug-resistant virus, associated with progressive and disseminated disease. We present a case report of a young male kidney recipient, who was CMV-seronegative with a CMV-seropositive donor (D(+)/R(-)), and who developed clinical GCV resistance, confirmed by mutation in viral UL97 phosphotransferase responsible for GCV activation. Under prophylactic therapy with intravenous GCV for 6 weeks post-transplantation, he developed severe anaemia and hepatic enzyme increases, probably due to drug side effects. At this moment, the drug was discontinued and he started to be monitored by pp65 antigen test. At week 10 post-transplantation, he presented fever, myalgia, thrombocytopenia and neutropaenia, with a positive CMV antigen test. During treatment with intravenous GCV, antigenaemia assay demonstrated a higher number of positive cells, requiring GCV at higher doses. Pre-emptive therapy lasted for 31 days and he started the maintenance therapy with oral GCV. However, antigenaemia assay demonstrated an extremely high number of positive cells, and he was rehospitalized and prescribed intravenous GCV. Severe leukopaenia led to GCV interruption, but immunosuppressive dose reduction helped to control the active CMV infection. GCV-resistant CMV infection resulted in increased morbidity, rehospitalization episodes and increased costs; therefore, implementation of resistance diagnostic tests in the transplantation routine is of great importance. We documented the first case of GCV-resistant CMV infection due to the L595S mutation in UL97 phosphotransferase gene in a kidney recipient from Bahia state, Brazil.

Assuntos

RESUMO

BACKGROUND: Low socioeconomic (SE) status has been associated to inflammation and predictors of C-reactive protein (CRP) have been investigated by studies performed in developed countries. This study aimed to identify predictors of CRP in individuals of very low SE level in a developing country and evaluate whether CRP is related to SE status in this scenario. OBJECTIVE: Eight-two individuals of very low SE level were recruited from a poor, semi-rural community in Brazil. Thirty-two individuals of high socioeconomic level comprised a comparison sample. High-sensitivity CRP was measured by nephelometry. METHODS: Eight-two individuals of very low SE level were recruited from a poor, semi-rural community in Brazil. Thirty-two individuals of high socioeconomic level comprised a comparison sample. High-sensitivity CRP was measured by nephelometry. RESULTS: In the low SE individuals, independent predictors of CRP were body mass index > 25 Kg/m(2) (P<0.001), smoking (P=0.005) and acute infection conditions (P=0.049). The low SE group (median=2.02 mg/l; interquartile range 0.92 - 4.95 mg/dl) had higher CRP levels compared to the high SE group (1.16 mg/l, interquartile range 0.55 - 2.50 mg/dl, P=0.03). Body mass index tended to be higher (27 +/- 4.9 kg/m(2) vs 25.5 +/- 3.2 kg/m(2); P=0.07) and the prevalence of acute infection greater (32% vs 3%, P=0.002) in the low SE group. After overweight individuals and those with infectious conditions were excluded, the CRP levels were similar between the groups with low and high SE levels (0.93 mg/l vs 1.08 mg/l, P=0.28). CONCLUSION: Adiposity, infection conditions and smoking are predictors of CRP in individuals with very low SE level. The first two factors determine greater level of inflammation in low SE individuals when compared to the high SE counterparts.

Assuntos

RESUMO

FUNDAMENTO: Inflamação sistêmica exacerbada tem sido descrita em indivíduos de baixo nível sócio-econômico, porém estudos sobre determinantes dos valores de proteína C-reativa foram realizados apenas em países desenvolvidos. OBJETIVO: Identificar preditores de PCR em indivíduos de baixo nível SE em um país em desenvolvimento e avaliar se a PCR está relacionada ao nível SE nesse cenário. MÉTODOS: Oitenta e oito indivíduos de nível SE muito baixo foram recrutados de uma comunidade pobre, semi-rural no Brasil; 32 indivíduos de nível SE alto foram utilizados como amostra de comparação. A PCR de alta sensibilidade foi medida por nefelometria. RESULTADOS: Entre os indivíduos de baixo nível SE, os preditores independentes de PCR foram índice de massa corporal > 25 kg/m² (P<0,001), hábito de fumar (P=0,005) e condições infecciosas agudas (P=0,049). O grupo com baixo nível SE (mediana=2,02 mg/l; variação interquartil: 0,92 - 4,95 mg/dl) apresentou níveis mais altos de PCR quando comparado com o grupo de alto nível SE (1,16 mg/l, variação interquartil: 0,55 - 2,50 mg/dl, P=0,03). O índice de massa corporal foi mais alto (27 ± 4,9 kg/m² vs 25,5 ± 3,2 kg/m²; P=0,07) e a prevalência de infecção aguda foi maior (32 por cento vs 3 por cento, P=0,002) no grupo com baixo nível SE. Após exclusão de indivíduos com sobrepeso ou condições infecciosas, os valores de PCR foram similares entre os grupos com baixo e alto nível SE (0,93 mg/l vs 1,08 mg/l, P=0,28). CONCLUSÃO: Adiposidade, condições infecciosas e fumo são preditores de PCR em indivíduos com nível SE muito baixo. Os primeiros dois fatores são os determinantes da exacerbação da inflamação em indivíduos de muito baixo nível SE.

BACKGROUND: Low socioeconomic (SE) status has been associated to inflammation and predictors of C-reactive protein (CRP) have been investigated by studies performed in developed countries. This study aimed to identify predictors of CRP in individuals of very low SE level in a developing country and evaluate whether CRP is related to SE status in this scenario. OBJECTIVE: Eight-two individuals of very low SE level were recruited from a poor, semi-rural community in Brazil. Thirty-two individuals of high socioeconomic level comprised a comparison sample. High-sensitivity CRP was measured by nephelometry. METHODS: Eight-two individuals of very low SE level were recruited from a poor, semi-rural community in Brazil. Thirty-two individuals of high socioeconomic level comprised a comparison sample. High-sensitivity CRP was measured by nephelometry. RESULTS: In the low SE individuals, independent predictors of CRP were body mass index > 25 Kg/m² (P<0.001), smoking (P=0.005) and acute infection conditions (P=0.049). The low SE group (median=2.02 mg/l; interquartile range 0.92 - 4.95 mg/dl) had higher CRP levels compared to the high SE group (1.16 mg/l, interquartile range 0.55 - 2.50 mg/dl, P=0.03). Body mass index tended to be higher (27 ± 4.9 kg/m² vs 25.5 ± 3.2 kg/m²; P=0.07) and the prevalence of acute infection greater (32 percent vs 3 percent, P=0.002) in the low SE group. After overweight individuals and those with infectious conditions were excluded, the CRP levels were similar between the groups with low and high SE levels (0.93 mg/l vs 1.08 mg/l, P=0.28). CONCLUSION: Adiposity, infection conditions and smoking are predictors of CRP in individuals with very low SE level. The first two factors determine greater level of inflammation in low SE individuals when compared to the high SE counterparts.

FUNDAMENTO: Se ha descrito inflamación sistémica exacerbada en individuos de bajo nivel socioeconómico, con todo, estudios sobre determinantes de los valores de proteína C reactiva sólo se han realizado en países desarrollo. OBJETIVO: Identificar predictores de PCR en individuos de bajo nivel SE en un país en desarrollo y evaluar si la PCR está relacionada al nivel SE en ese escenario. MÉTODOS: Se reclutaron ochenta y ocho individuos de nivel SE muy bajo de un comunidad pobre, semi-rural en Brasil, se utilizaron 32 individuos de nivel SE alto como muestra de comparación. La PCR de alta sensibilidad se midió por nefelometría. RESULTADOS: Entre los individuos de bajo nivel SE, los predictores independientes de PCR fueron índice de masa corporal > 25 kg/m² (P<0,001), hábito de fumar (P=0,005) y condiciones infecciosas agudas (P=0,049). El grupo con bajo nivel SE (mediana=2,02 mg/l; variación intercuartil: 0,92 - 4,95 mg/dl) presentó niveles más altos de PCR al compararlo con el grupo de alto nivel SE (1,16 mg/l, variación intercuartil: 0,55 - 2,50 mg/dl, P=0,03). El índice de masa corporal fue más alto (27 ± 4,9 kg/m² vs 25,5 ± 3,2 kg/m²; P=0,07) y la prevalencia de infección aguda fue mayor (32 por ciento vs 3 por ciento, P=0,002) en el grupo con bajo nivel SE. Tras la exclusión de individuos con sobrepeso o condiciones infecciosas, los valores de PCR fueron similares entre los grupos con bajo y alto nivel SE (0,93 mg/l vs 1,08 mg/l, P=0,28). CONCLUSIÓN: Adiposidad, condiciones infecciosas y tabaco son predictores de PCR en individuos con nivel SE muy bajo. Los primeros dos factores son los determinantes de la exacerbación de la inflamación en individuos de muy bajo nivel SE.

Assuntos

RESUMO

In vitro spontaneous proliferation is the immunological hallmark of peripheral blood mononuclear cells (PBMC) from HTLV-1-infected individuals. Quinoline compounds down regulate in vitro cell proliferation of HTLV-1 transformed cell lines. In the present study we assessed the capacity of quinolines to inhibit spontaneous cell proliferation of PBMC from HTLV-1-infected individuals. Twenty-two quinolines were evaluated. Toxicity was first assessed on PBMC from healthy donors by using both the Trypan blue technique and Tetrazolium Salt (XTT) method and then the antiproliferative effect was measured by a classic lymphoproliferative assay on PBMC from three HTLV-1-infected individuals, in the presence of decreasing concentrations of quinolines (from 100microM to 0.8microM), after 5 days of culture. We found that 14 out of 22 compounds were non-toxic to PBMC from uninfected individuals at 100, 50 and 10microM. Four compounds presented a capacity to inhibit more than 80% of the spontaneous proliferation: 7 at 25microM and 10, 20 and 23 at 100microM. Our results indicate that some quinolines block spontaneous proliferation of PBMC from HTLV-1-infected individuals.

Assuntos