Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy.

BACKGROUND: In many preclinical AIDS research studies, antiretroviral therapy (ART) is administered to experimentally simian immunodeficiency (SIV)-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r)-(phosphonomethoxy) propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily) can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily) starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine; emtricitabine) and stavudine (d4T). RESULTS: In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals) and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals). While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN) and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. CONCLUSIONS: Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies.

Perfil de alimentación y nutrición de mujeres en edad fértil de un municipio del centroccidente de venezuela / Feeding and nutrition profile of fertile age women from a west-center township in venezuela

Con el objetivo de identificar el estado nutricional y alimentación de las mujeres de 12 a 45 años del Municipio Jiménez, Estado Lara, Venezuela, se realizó un estudio de prevalencia entre septiembre 2007 y abril 2008. La muestra consistió de 243 mujeres seleccionadas a través de una muestra aleatoria estratificada según sectores rural- urbano, por conglomerados. Cada participante respondió un cuestionario con datos personales y socioeconómicos, se le tomó peso, talla, circunferencia media del brazo, pliegues tricipital y subescapular y se calculó el índice de masa corporal y los indicadores de composición corporal, utilizando referencias internacionales y nacionales. La evaluación dietética consistió en una encuesta de frecuencia de consumo y 2 recordatorios de 24 horas. 46,6% presentaron exceso de peso, más frecuente en mujeres adultas, mientras que el déficit de peso fue de 8,3%, más frecuente en adolescentes (p=0,000) y 44,1% presentó exceso de grasa corporal. Se observó deficiencia importante en la adecuación de consumo de calcio (34,7%), zinc (20,9%), cobre (13,3%), folatos (41,5%), vitaminas B6 (19,8%), vitamina C (62,6%), proteínas (72,0%) y calorías (58,1%). Más del 90% de la muestra consumían diariamente cereales y grasas visibles, con menor frecuencia lácteos (61,7%), carnes y huevos (76,5%), leguminosas (17%), frutas (40,0%), vegetales (14,0%). En la población estudiada coexiste una importante prevalencia de déficit y exceso de peso, así como hábitos alimenticios inadecuados, lo cual amerita programas de intervención para disminuir los riesgos de enfermedades crónicas y mortalidad(AU)

The objective was to study the nutritional status and food habits of women of childbearing age (12 to 45 years) from Municipio Jimenez, Lara State, Venezuela. The sample consisted in 243 women, randomly selected from rural and urban conglomerates of the Municipio. Each woman was requested to fill a questionnaire, with personal and socioeconomic information, between September 2007 and April 2008. Weight, height, mid arm circumferences and skinfolds were obtained. The body mass index and composition indicators were calculated. The nutritional status of the group was classified according to national and international standards. Dietetic evaluation consisted in one food frequency and two food recall questionnaires. Overweight was present in 46.6% of women, being higher in adult women, low weight affected 8.3% being significantly more frequent in adolescents (p=0,000). There were important deficiencies in consumption adequacy of calcium (34.7%), zinc (20.9%), copper (13.3%), folates (41.5%), vitamins B6 (19.8%), C (62.6%), proteins (72.0%) and calories (58.1%). Cereals and edible fats were consumed daily by more than 90% of the sample. Intake of dairy products (61.7%), meats and eggs (76.5%), grains (17.0%), fruits (40.0%), and vegetables (14.0%), was less frequent. In conclusion, the population studied showed the simultaneous co-existence of excess and deficit of weight as well as inadequate food habits, that justify the implementation of intervention programs to diminish mortality and the risk of non-transmissible chronic diseases(AU)

Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm.

BACKGROUND: At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1) infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. RESULTS: Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC50 was

Folatos y hierro en mujeres en edad fértil de una comunidad en Venezuela afectada por la incidencia de defectos del tubo neural / Folate and iron in fertile age women from a Venezuelan community affected by incidence of neural tube defects

El objetivo de este estudio transversal fue identificar el estado nutricional de folatos y hierro en mujeres en edad fértil del Municipio Jiménez, Estado Lara, Venezuela. El muestreo fue probabilístico por conglomerados del área urbana y rural, seleccionándose 15 conglomerados donde se estudiaron a las mujeres entre 12 y 45 años (269 mujeres). Previa firma del consentimiento informado, se les practicó: Encuesta con datos personales, antecedentes y variables relacionadas con folatos y hierro; datos socioeconómicos (Encuesta Graffar-Méndez Castellano y Necesidades Básicas Insatisfechas); en muestra de sangre se determinó Hemoglobina y Folato Eritrocitario (FE); en suero se determinó Ferritina, y Folato Sérico (FS). 53,53% de la muestra presentó valores bajos de FS, y el 10,78% valores deficientes. 80,7% presentó deficiencia severa según FE y 5,9% deficiencia moderada. En ambas pruebas, la media fue mayor en mujeres tratadas con Acido Fólico ó embarazadas (p=0,000) y la media del FE también resultó mayor en adultas que adolescentes (p=0,001) y en mujeres no pobres (p=0,011); no hubo diferencias significativas según ingesta de café, alcohol, anticonceptivos, procedencia, estrato social. La anemia se determinó en 11,2%, más frecuente en adultas (p=0,029) y en las del medio urbano (p=0,042). Ferritina baja se encontró en 37.3% de la muestra, las diferencias según variables no fueron significativas. En conclusión, la prevalencia de deficiencia de hierro y folatos en mujeres en edad fértil del Municipio Jiménez es alta, ésta podría constituir un factor condicionante de defectos del tubo neural, por lo cual deben ejecutarse estrategias para superar este déficit.

The objective of this transversal study was to determine folate and iron nutritional status of women in fertile age from Municipio Jiménez, Lara State, Venezuela. The sampling was probabilistic by conglomerates from the urban and rural areas, selecting 15 conglomerates from which women between 12 and 45 years (269), were studied. After signing informed consent, participating were interviewed for personal data, antecedents related to folate and iron, socioeconomic data (Graffar-Mendez Castellano method and unsatisfied basic needs). In blood sample was determined Hemoglobin, and Erythrocytic Folate (FE). Serum was obtained to determine Ferritin and Serum Folate (FS). 53,53% of the sample presented low FS levels, 10.78% were FS deficient. Severe FE deficiency was present in 80.7% of the cases, moderate deficiency affected 5,9%. For both tests, median was higher for women in treatment with Acido Fólico or pregnant (p=0,000), median for FE was higher for adults (p=0.001) and in non poor women (p=0.011). There were no significant differences for coffee, alcohol, anticonceptive consumption, urban or rural resident or socioeconomic strata. The prevalence of anemia was 11,2% being significantly more frequent in adults than in adolescents (p= 0,029) and in urban women (p=0,042). Low ferritin were found in 37,3% of the sample, the effect of different variables was not statistically significant. In conclusion, there is a high prevalence of iron and folate deficiencies in women of fertile age from Municipio Jiménez, which could constitute a conditioning factor for the appearance of neural tube defects.

Depo-Provera does not alter disease progression in SIVmac-infected female Chinese rhesus macaques.

Depo-Provera (medroxyprogesterone acetate), a long-acting derivative of progesterone, is utilized during many nonhuman primate microbicide studies to facilitate simian immunodeficiency virus (SIV) infection by thinning the vaginal epithelium. To date, the systemic effects of this steroid hormone in regard to SIV/HIV pathogenesis are not well understood, but an increase in infection rates and lymphoproliferation following progesterone application has been reported. Therefore, a proactive study using 20 Chinese rhesus macaques was designed to investigate the effect of a single Depo-Provera injection on SIV disease progression. Group 1 (n = 10) was treated with 30 mg Depo-Provera intramuscularly 30 days prior to intravenous challenge with 50 TCID(50) SIVmac251, while Group 2 (n = 10) remained untreated, but received the same amount of SIV. Blood samples were taken at predetermined intervals to measure RNA viral loads, CD4(+), CD8(+), and CD20(+) lymphocyte counts and percentages and absolute numbers of naive and memory T lymphocytes. Upon statistical endpoint data analysis, none of the parameters measured were shown to be significantly different between the groups. One animal in the Depo-Provera-treated group and two macaques in the control group were euthanized prior to study end due to the development of clinical signs (in weeks 43 and 51, respectively). All other animals were euthanized between weeks 68 and 71 post-SIV infection. Histopathological evaluations revealed that 5 of 10 animals in each group had developed simian AIDS (SAIDS). In summary, this prospective study demonstrated that a single injection of 30 mg Depo-Provera did not have a significant influence on SIV disease progression.

[Epidemiological study of preoperative anaemia in surgical oncology patients in Spain. RECIRON Study]. / Estudio epidemiológico de la anemia preoperatoria en pacientes sometidos a cirugía oncológica en España. Estudio RECIRON.

INTRODUCTION: Anaemia is common in oncology patients who are going to have surgery for tumour resection. Allogenic blood transfusion has been associated with a greater incidence of postoperative complications. The aim of this study is to analyse current clinical practice as regards the preoperative treatment and conditions of these patients in Spain. MATERIAL AND METHOD: This is an epidemiological observational study which included 472 patients from different hospitals. The data included in the clinical history was analysed: tumour location, preoperative laboratory tests, functional situation (Karnofsky index [KI]), anaemia treatment and transfusions given since the diagnosis. RESULTS: As regards the tumour location, 181 were urological (38.3%), 161 digestive system (34.1%), and 130 gynaecological (27.5%). The time from the initial diagnosis until surgical intervention was 6.2+/-6 weeks, and 19.1+/-23 days from the anaesthetist visit to the surgical operation. The mean pre-operative haemoglobin (Hb) was 13.1+/-2 g/dl. The anaemia was treated in 12.9% of the patients and 15% (69 patients) received a transfusion before surgery. A total of 28.1% patients had a KI< or =80. The lowest preoperative haemoglobin levels are associated with the lowest KI. CONCLUSIONS: Anaemia is present in a high percentage of oncology patients who are going to be surgically treated. Preoperative blood transfusion is the most common treatment. It was observed that there is sufficient preoperative time to be able to improve preparation of the patient for surgery.

Estudio epidemiológico de la anemia preoperatoriaen pacientes sometidos a cirugía oncológica en España. Estudio RECIRON / Epidemiological study of preoperative anaemia in surgical oncology patients in Spain. RECIRON Study

Introducción: la anemia es frecuente en el paciente oncológico que va a ser sometido a cirugía para resección tumoral. La transfusión de sangre alogénica se ha relacionado con una mayor incidencia de complicaciones postoperatorias. El objetivo de este estudio es analizarla práctica clínica actual en relación con el tratamiento y las condiciones preoperatorias de estos pacientes en nuestro medio. Material y método: se trata de un estudio observacional epidemiológico en el que se incluye a472 pacientes procedentes de distintos hospitales. Se analizan los datos incluidos en la historia clínica: localización tumoral, analítica preoperatoria, situación funcional (índice de Karnofsky [IK]), tratamiento de la anemia y transfusiones realizadas desde el diagnóstico. Resultados: Según la localización tumoral, hay 181 tumores urológicos (38,3%), 161 digestivos(34,1%) y 130 ginecológicos (27,5%). El tiempo transcurrido desde el momento del diagnóstico hasta la intervención quirúrgica fue de 6,2 ± 6 semanas, y 19,1 ± 23 días desde la consulta de preanestesia hasta la intervención quirúrgica. La hemoglobina (Hb) preoperatoria media fue 13,1 ± 2 g/dl. En el 12,9% de los pacientes se trató la anemia y un 15%(69 pacientes) recibió alguna transfusión antes de la cirugía. El 28,1% de los pacientes presentaban un IK ≤ 80. Las cifras preoperatorias de Hb más bajas se relacionan con los IK más bajos. Conclusiones: un porcentaje elevado de pacientes oncológicos que van a ser tratados quirúrgicamente tienen anemia. La transfusión de sangre preoperatoria es el tratamiento más frecuente. Se observa que hay un tiempo preoperatorio suficiente que permitiría mejorarla preparación del paciente para la intervención quirúrgica (AU)

Introduction: Anaemia is common in oncology patients who are going to have surgery for tumour resection. Allogenic blood transfusion has been associated with a greater incidence of postoperative complications. The aim of this study is to analyse current clinical practice as regards the preoperative treatment and conditions of these patients in Spain. Material and method: This is an epidemiological observational study which included 472patients from different hospitals. The data included in the clinical history was analysed: tumour location, preoperative laboratory tests, functional situation (Karnofsky index [KI]), anaemia treatment and transfusions given since the diagnosis. Results: As regards the tumour location, 181 were urological (38.3%), 161 digestive system(34.1%), and 130 gynaecological (27.5%). The time from the initial diagnosis until surgical intervention was 6.2±6 weeks, and 19.1±23 days from the anesthetist visit to the surgical operation. The mean pre-operative haemoglobin (Hb) was 13.1±2 g/dl. The anaemia was treated in 12.9% of the patients and 15% (69 patients) received a transfusion before surgery. A total of 28.1% patients had a KI≤80. The lowest preoperative (..) (AU)

A therapeutic SIV DNA vaccine elicits T-cell immune responses, but no sustained control of viremia in SIVmac239-infected rhesus macaques.

The immunologic and virologic outcome of therapeutic DNA-vaccines administered during antiretroviral therapy (ART) using electroporation with or without (interleukin) IL-2 treatment was evaluated in the SIVmac239/macaque model. Rhesus macaques inoculated with pathogenic SIVmac239 were treated with ART [(R(-9-(2-phosphonomethoxypropyl) adenine) (PMPA), FTC, Zerit] from weeks 13 to 41 postinfection (wpi). Group 1 (n = 7) received ART only, groups 2 and 3 (each n = 6) additionally received SIVmac239-derived gp140Env, GagPol, and TatRevNef plasmids by in vivo electroporation at 22, 26, 30, and 34 wpi, and group 3 also IL-2 for 14 days after each vaccination. Endpoints evaluated were viral load, Gag(181189)-specific CD8+ T-cell responses in MamuA01+ animals, lymphoproliferative responses, and CD4 T-cell counts. Viremia in all animals dropped below 200 RNA copies/ml during ART. Frequencies of Gag(181189)-specific CD8+ T cells prior to ART were detectable in all three groups (1.27-3.01%) and increased significantly (p < 0.01) postvaccination with maximum responses after the fourth immunization (0.2% versus 3.49-7.15%). Gag(181189)-specific CD8+ T-cell frequencies increased post-ART cessation in all groups and remained at significantly higher levels (p < 0.001) until the end of the study (75 wpi) in both groups of vaccinated animals. Lymphoproliferative responses were detected against Gag in a limited number of animals after vaccination and post-ART. However, plasma RNA viral loads rebounded after ART termination to similar levels in all three groups, but remained below 10(5) copies/ml until the end of the study, which could be a late effect of the triple drug therapy.

Uso del método: necesidades básicas insatisfechas en la detección de comunidades con riesgo de desnutrición / Use of the: unsatisfied basic needs methods in the detection of comunities with undernutrition risk

Con el objetivo de evaluar la aplicación del Método Necesidades Básicas Insatisfechas (NBI) en la detección de comunidades con mayor riesgo de desnutrición en los primeros 6 años de vida, se realizó un estudio de prevalencia en la Parroquia Juan Villegas, Barquisimeto, Venezuela. De la población de niños del grupo de edad de la zona, se obtuvo una muestra aleatoria estratificada y por conglomerados; se constituyeron cinco gradientes de barrios según el porcentaje de hogares con NBI. Se evaluaron 538 niños en 16 barrios a través de indicadores de NBI en la familia, encuesta Graffar Méndez Castellano peso y talla. El 10.8 por ciento de la muestra presentó desnutrición actual, el 25.3 por ciento déficit talla/edad, y el 5.8 por ciento sobrepeso; el porcentaje de niños con déficit nutricional crónico fue mayor en los gradientes NBI con peores condiciones de vida, siendo 30 por ciento en los barrios con 60-100 por ciento NBI. La presencia de viviendas inapropiadas, sin algún servicio básico, bajo nivel educativo de la madre, ingresos familiares tipo donaciones, y residencia en barrios con 60-100 por ciento NBI se asoció con mayor riesgo de presentar déficit talla/edad (riesgo relativo estimado:1.55, 1.29, 1.35, 2.43 y 1.2 respectivamente). El riesgo de déficit peso/edad fue mayor en quienes habitan viviendas inadecuadas, cuando existe hacinamiento crítico ó jefe de familia obrero no especializado (riesgo relativo estimado: 1.56, 1.34 y 1.39 respectivamente). El método utilizado ofrece ventajas para identificar las localidades y familias con mayor riesgo de desnutrición infantil, a fin de establecer en ellos programas de intervención nutricional

Vitamina A en niños menores de 7 años de comunidades suburbanas: Barquisimeto-Venezuela / Vitamin A in children from suburban communities: Barquisimeto-Venezuela

Con el objetivo de evaluar el estado nutricional de vitamina A en niños de siete años de comunidades suburbanas de Barquisimeto se realizó un estudio de corte transversal. Los barrios de la Parroquia Juan de Villegas (oeste de Barquisimeto) fueron clasificados en cinco estratos según el porcentaje de hogares con necesidades básicas insatifechas. Se realizó un muestreo estratificado por conglomerados, para seleccionar una muestra de 292 niños. A cada niño se le evaluó el estado nutricional por antropometría, el estrato socioeconómico por el método Graffar-Méndez-Castellano, y el retinol sérico por el método HPLC. En el 14 por ciento de la muestra se encontraron valores bajos de retinol (< 20 ug/dl), en el 55,1 por ciento valores marginales (20-29 ug/dl) y en el 30,8 por ciento valores normales. No se encontraron diferencias significativas en el promedio de retinol sérico según sexo, grupo de edad, estado nutricional y condiciones de vida, aunque se apreció una tendencia a mayor porcentaje de valores normales a mejores condiciones de vida. Los niños residentes en viviendas inadecuadas, sin servicios básicos, presentaron 2,3 veces mayor riesgo de deficiencia de vitamina A. Se encontró un porcentaje importante de niños con déficit subclínico de vitamina A, lo cual amerita programas específicos de prevención en el ámbito local, así como la investigación de la situación de este nutriente en el país