Incidence of childhood cancer in Latin America and the Caribbean: coverage, patterns, and time trends / Incidencia del cáncer infantil en América Latina y el Caribe: cobertura de los registros, patrones y tendencias a lo largo del tiempo / Incidência de câncer infantil na América Latina e no Caribe: cobertura, padrões e tendências temporais

ABSTRACT Objective. To provide a comprehensive overview of geographical patterns (2001-2010) and time trends (1993-2012) of cancer incidence in children aged 0-19 years in Latin America and the Caribbean (LAC) and interpret the findings in the context of global patterns. Methods. Geographical variations in 2001-2010 and incidence trends over 1993-2012 in the population of LAC younger than 20 years were described using the database of the third volume of the International Incidence of Childhood Cancer study containing comparable data. Age-specific incidence per million person-years (ASR) was calculated for population subgroups and age-standardized (WSR) using the world standard population. Results. Overall, 36 744 unique cases were included in this study. In 2001-2010 the overall WSR in age 0-14 years was 132.6. The most frequent were leukemia (WSR 48.7), central nervous system neoplasms (WSR 23.0), and lymphoma (WSR 16.6). The overall ASR in age group 15-19 years was 152.3 with lymphoma ranking first (ASR 30.2). Incidence was higher in males than in females, and higher in South America than in Central America and the Caribbean. Compared with global data LAC incidence was lower overall, except for leukemia and lymphoma at age 0-14 years and the other and unspecified tumors at any age. Overall incidence at age 0-19 years increased by 1.0% per year (95% CI [0.6, 1.3]) over 1993-2012. The included registries covered 16% of population aged 0-14 years and 10% of population aged 15-19 years. Conclusions. The observed patterns provide a baseline to assess the status and evolution of childhood cancer occurrence in the region. Extended and sustained support of cancer registration is required to improve representativeness and timeliness of data for childhood cancer control in LAC.

resumen está disponible en el texto completo

RESUMO Objetivo. Apresentar uma visão abrangente dos padrões geográficos (2001 a 2010) e das tendências temporais (1993 a 2012) da incidência de câncer em crianças e jovens de 0 a 19 anos na América Latina e no Caribe (ALC) e interpretar os resultados no contexto de padrões mundiais. Métodos. Foram descritas variações geográficas de 2001 a 2010 e tendências de incidência de 1993 a 2012 na população com menos de 20 anos da ALC usando informações comparáveis da base de dados do terceiro volume do estudo International Incidence of Childhood Cancer. Foram calculadas taxas de incidência específica por idade por milhão de pessoas-ano (ASR, na sigla em inglês) para subgrupos populacionais e taxas padronizadas por idade usando a população padrão mundial (WSR, na sigla em inglês). Resultados. No total, foram incluídos 36 744 casos únicos. No período de 2001 a 2010, a WSR para todos os tumores combinados na faixa etária de 0 a 14 anos foi de 132,6. Os diagnósticos mais frequentes foram leucemia (WSR de 48,7), neoplasias do sistema nervoso central (WSR de 23,0) e linfoma (WSR de 16,6). A ASR para todos os tumores combinados na faixa etária de 15 a 19 anos foi de 152,3, e a maior taxa foi a de linfoma (ASR de 30,2). A incidência foi maior no sexo masculino do que no sexo feminino e maior na América do Sul do que na América Central e no Caribe. De modo geral, em comparação com as estimativas mundiais, a incidência na ALC foi menor, exceto para leucemia e linfoma entre 0 e 14 anos e para outros tumores e tumores não especificados em qualquer idade. A taxa de incidência na faixa etária de 0 a 19 anos aumentou em 1,0% ao ano (IC de 95% [0,6, 1,3]) entre 1993 e 2012. Os registros incluídos cobriam 16% da população de 0 a 14 anos e 10% da população de 15 a 19 anos. Conclusões. Os padrões observados servem de referência para avaliar o status e a evolução da ocorrência de câncer infantil na região. É necessário garantir um apoio ampliado e consistente aos registros de câncer para aprimorar a representatividade e a disponibilidade das informações em tempo adequado para o controle do câncer infantil na ALC.

Cáncer colorrectal ­ diagnóstico y tratamiento: revisión bibliográfica / Colorectal cancer ­ diagnosis and treatment: literature review

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Although improvements in detection and treatment have been implemented; CRC incidence, prevalence, and mortality remain high, even in developed countries. The risk of developing this cancer is related to poor eating habits, smoking, inflammatory bowel disease, polyps, genetic factors, and aging. There are several methods for detecting colorectal cancer, including the guaiac test, stool immunochemical test, stool DNA test, sigmoidoscopy, colonoscopy, and barium enema. The stage at which the cancer is detected determines the patient's prognosis, survival, and treatment. Treatments include endoscopic and surgical local excision, preoperative radiation therapy and systemic downstage therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, and palliative, targeted chemotherapy and immunotherapy.

El cáncer colorrectal (CCR) es el tercer cáncer más prevalente a nivel mundial. A pesar de que se han implementado mejoras en la detección y el tratamiento; la incidencia, la prevalencia y la mortalidad del CCR siguen siendo altas, incluso en países desarrollados. El riesgo de desarrollar este cáncer está relacionado con malos hábitos alimentarios, tabaquismo, enfermedad inflamatoria intestinal, pólipos, factores genéticos y envejecimiento. Existen varios métodos para detectar el cáncer colorrectal, como la prueba de guayaco, la prueba inmunoquímica de heces, la prueba de ADN en heces, la sigmoidoscopia, la colonoscopia y el enema de bario. El estadio en el que se detecta el cáncer determina el pronóstico, la supervivencia y el tratamiento del paciente. Los tratamientos incluyen escisión local endoscópica y quirúrgica, radioterapia preoperatoria y terapia sistémica de reducción del estadio, cirugía extensa para enfermedad locorregional y metastásica, terapias ablativas locales para metástasis y quimioterapia paliativa, terapia dirigida e inmunoterapia.

Evaluación de la presencia de COVID-persistente en los pacientes de la farmacia comunitaria en la Comunidad de Madrid / Evaluation of the presence of COVID-persistent in patients in community pharmacy in the Community of Madrid

INTRODUCCIÓN: algunos de los síntomas de COVID-19 continúan semanas o meses después de la infección, sin la existencia de un daño orgánico. Esta afección es lo que ha pasado a denominarse COVID persistente.OBJETIVOS: - Relacionar la gravedad de la COVID persistente con el estilo de vida y las patologías previas crónicas- Medir la percepción del cambio en la calidad de vida.MATERIAL Y MÉTODO: se ha realizado un estudio retrospectivo, observacional, descriptivo, individual y de corte transversal, mediante un cuestionario de forma anónima. Criterios de inclusión: pacientes que entraban a la farmacia, que habían padecido previamente COVID-19 y respondían a la encuesta. Criterios de exclusión: pacientes de la farmacia que no respondían la encuesta o que no habían padecido la COVID-19.RESULTADOS: se incluyeron en el estudio 174 participantes. La incidencia de contagios de nuestros pacientes coincide con los picos de las distintas olas de COVID-19.El 66.6 % de los pacientes perciben que la intensidad de sintomatología de COVID persistente es baja, con una percepción de mayor gravedad en personas mayores. El 96,7 % de los pacientes que fueron hospitalizados con COVID dicen que la COVID persistente no les afecta en su calidad de vida .El 88,4 % no estaban tratando sus síntomas frente a un 11,6 % que sí lo hacía. 24.78 % eran fumadores. Entre estos, los síntomas que más se repetían eran la fatiga (17,8 %), la pérdida de cabello (12,3 %), los trastornos olfativos (9,6 %) y los problemas cutáneos (9,6 %). Entre las personas no fumadoras encontrábamos fatiga (28,3%), pérdida de cabello (16,1 %), desórdenes del sueño (11,1 %) y dolor en las articulaciones (9,4%). El 88,4% de los pacientes con patologías previas decían que los síntomas de COVID persistente afectaba su calidad de vida poco o nada. (AU)

Increased severity in SARS-CoV-2 infection of minorities in Spain.

OBJECTIVE: With the global spread of COVID-19, studies in the US and UK have shown that certain communities have been strongly impacted by COVID-19 in terms of incidence and mortality. The objective of the study was to determine social determinants of health among COVID-19 patients hospitalized in the two major cities of Spain. METHODS: A multicenter retrospective case series study was performed collecting administrative databases of all COVID-19 patients ≥18 years belonging to two centers in Madrid and two in Barcelona (Spain) collecting data from 1st March to 15th April 2020. Variables obtained age, gender, birthplace and residence ZIP code. From ZIP code we obtained per capita income of the area. Predictors of the outcomes were explored through generalized linear mixed-effects models, using center as random effect. RESULTS: There were 5,235 patients included in the analysis. After multivariable analysis adjusted by age, sex, per capita income, population density, hospital experience, center and hospital saturation, patients born in Latin American countries were found to have an increase in ICU admission rates (OR 1.56 [1.13-2.15], p<0.01) but no differences were found in the same model regarding mortality (OR 1.35 [0.95-1.92], p=0.09). CONCLUSIONS: COVID-19 severity varies widely, not only depending on biological but also socio-economic factors. With the emerging evidence that this subset of population is at higher risk of poorer outcomes, targeted public health strategies and studies are needed.

Análisis de cumplimentación de las recetas médicas en soporte papel / Analysis of completion of medical prescriptions on paper

Dentro de las políticas farmacéuticas, el Estado se ha interesado por la receta médica como documento legal de prescripción y de dispensación de medicamentos y productos sanitarios, contribuyendo a la mejora en la seguridad del paciente. Con el objetivo de medir la cumplimentación de las recetas que llegan a la farmacia comunitaria se realizó un estudio observacional transversal, durante dos meses de 2019, revisando todas las recetas en soporte papel presentadas para su dispensación en cinco farmacias. En ese intervalo se recibieron un total de 33.463 recetas, 30.085 (89,90 %) eran electrónicas y 3.378 (10,10 %) en papel. De estas, 841 (25 %) eran del Sistema Nacional de Salud (SNS), 931 (27 %) de MUFACE, 362 (11 %) de ISFAS, 28 (1 %) de MUGEJU, 201 (6 %) de otras mutuas y 1.015 (30 %) de asistencia sanitaria privada. Cuando se analizó el número y porcentaje de recetas en papel que podían ser dispensadas legalmente, se observó que sólo 130 (65 %) recetas de otras mutuas, 30 (4 %) recetas del SNS y 34 (3 %) recetas privadas estaban correctamente cumplimentadas. Por tanto, sólo 194 de las 3.378 recetas en papel analizadas (6 %) que se han recibido durante dos meses en las cinco farmacias podían ser dispensadas de acuerdo con la ley actual. Cuando las recetas no están correctamente cumplimentadas, con los datos básicos obligatorios, indispensables para la validez de la receta médica, la seguridad del paciente puede verse comprometida y los profesionales sanitarios que prescriben y los que dispensan los medicamentos se exponen a sanciones

Within the pharmaceutical policies, the State has been interested in the medical prescription as a legal document of prescription and dispensing medicines and health products contributing to the improvement in patient safety. To measure the degree of compliance of the prescriptions that arrive at the community pharmacy, a cross-sectional observational study was conducted for two months of 2019 to review all the prescriptions on paper presented for dispensing in five pharmacies. Within this period, a total of 33463 prescriptions were received 30085 (89.90%) were electronic and 3378 (10.10%) were on paper. Of these, 841 (25%) came from the public health system, 931 (27%) from MUFACE, 362 (11%) from ISFAS, 28 (1%) from MUGEJU, 201 (6%) other organizations and 1015 (30%) from private healthcare. When the number and percentage of paper prescriptions that could be legally dispensed was analysed, it was observed that only 130 (65%) prescriptions of other organizations, 30 (4%) of the public health system and 34 (3%) of private healthcare were correctly completed. Therefore, only 194 of the 3,378 paper prescriptions (6%) received during two months in the five community pharmacies could be dispensed according to current law. When the prescriptions are not correctly filled, with the mandatory basic data, indispensable for the validity of the medical prescription, the patient's safety can be compromised and the prescribing health professionals and those who dispense the medications are exposed to sanctions

Hemorragia foveal en paciente inmunocompetente con leishmaniasis visceral / Foveal hemorrhage in an immunocompetent patient with visceral leishmaniasis

OBJETIVO: Comunicar un caso de hemorragias foveal e intrarretinal macular en paciente inmunocompetente con leishmaniasis visceral. CASO CLÍNICO: Hombre de 42 años inmunocompetente, se presentó con pérdida visual progresiva y metamorfopsia en el ojo derecho. En el examen del fondo de ojo se encontró una lesión amarilla redonda foveal y hemorragias intrarretinales en la mácula. El paciente fue hospitalizado con fiebre, anorexia, pérdida de peso, hepatoesplenomegalia y anemia progresiva. Se realizaron estudios de laboratorio que fueron positivos para la leishmaniasis y hepatitis A. El tratamiento se inició con anfotericina B 50 mg/día hasta una dosis total de 1.400 mg. CONCLUSIÓN: Hemorragias retinales bilaterales en un país endémico podrían indicar el diagnóstico de leishmaniasis visceral

OBJECTIVE: To report a case of foveal and macular intraretinal hemorrhages in an immunocompetent male patient with visceral leishmaniasis. CASE REPORT: An immunocompetent, 42 year-old male, presented with progressive visual loss and metamorphopsia in his right eye. The fundus examination showed a foveal round yellow lesion and intraretinal hemorrhages in the macula. The patient was hospitalized with fever, anorexia, weight loss, hepatosplenomegaly, and progressive anemia. Laboratory studies were conducted and a positive test for leishmaniasis and hepatitis A was reported. Treatment was begun with amphotericin B 50 mg/day up to a total dose of 1400 mg. CONCLUSION: Bilateral retinal hemorrhages in an endemic country could suggest the diagnosis of visceral leishmaniasis

Foveal hemorrhage in an immunocompetent patient with visceral leishmaniasis.

OBJECTIVE: To report a case of foveal and macular intraretinal hemorrhages in an immunocompetent male patient with visceral leishmaniasis. CASE REPORT: An immunocompetent, 42 year-old male, presented with progressive visual loss and metamorphopsia in his right eye. The fundus examination showed a foveal round yellow lesion and intraretinal hemorrhages in the macula. The patient was hospitalized with fever, anorexia, weight loss, hepatosplenomegaly, and progressive anemia. Laboratory studies were conducted and a positive test for leishmaniasis and hepatitis A was reported. Treatment was begun with amphotericin B 50mg/day up to a total dose of 1400mg. CONCLUSION: Bilateral retinal hemorrhages in an endemic country could suggest the diagnosis of visceral leishmaniasis.

4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast.

Cardiac fibroblast (CF) survival is important for the maintenance of the extracellular matrix homeostasis in the heart; providing a functional support to cardiomyocytes necessary for the correct myocardial function. Endoplasmic reticulum (ER) stress causes cellular dysfunction and cell death by apoptosis; and thapsigargin is a well-known ER stress inducer. On the other hand, the chemical chaperone, 4-phenylbutyric acid (4-PBA) had showed to prevent ER stress; however, in cardiac fibroblast both the ER stress induced by thapsigargin and prevention by 4-PBA, have not been studied in detail. Neonate rat CF were treated with thapsigargin in presence or absence of 4-PBA, and cell viability was evaluated by trypan blue exclusion and apoptosis by flow cytometry; whereas CHOP, BIP, PDI, ATF4 and procollagen protein levels were assessed by western blot. In CF, thapsigargin triggered the unfolded protein response detected by early increases in ATF4, CHOP, PDI and BIP protein levels as well as, the accumulation of intracellular procollagen. Thapsigargin also stimulated CF death in a time and concentration-dependent manner. ER stress, CF death and apoptosis induced by thapsigargin were prevented by 4-PBA. Conclusion our data suggest that 4-PBA prevent ER stress, intracellular procollagen accumulation, CF death and apoptosis induced by thapsigargin.

Molecular Crossroads of Frailty and HIV.

An epidemiological transition is occurring regarding Human Immunodeficiency Virus (HIV) infection. This phenomenon, explained by several mechanisms (e.g.: physiologic changes, pharmacologic advances, sexual behaviors), is demonstrated by a significant increase in the number of patients aged 50 years and older diagnosed with this infection. The immunological changes observed in HIV-infected patients may prompt the appearance of an accelerated aging process as well as that of comorbidities and other pathological entities commonly diagnosed in older adults. Frailty is a biologic syndrome characterized by a multi-systemic decrease of the individual's physiologic and homeostatic reserves, leading to diminished resistance against stressors and increased vulnerability. The purpose of this review is to describe the common molecular changes seen in both frailty and HIV-1 infection, offering an in-depth analysis of their pathophysiology and specifying common processes where their pathways meet.

Percepción de bienestar social y participación política en adultos de una comunidad rural en Minga Guazú, Alto Paraná / Hope and social well-being and political participation in adults belonging to a rural community of Minga Guazú, Alto Par

El objetivo principal de esta investigación es determinar la correlación entre el Bienestar Social y la Participación Política en adultos pertenecientes a una Comunidad Rural de Minga Guazú, Alto Paraná. La muestra está conformada por 70 adultos, sin discriminación de sexo. Se aplicó un diseño descriptivo y correlacional. El análisis de datos se realizó a través del Coeficiente de Correlación Lineal R de Pearson, obteniendo una relación positiva entre las dos escalas relacionadas. Se concluye que el Bienestar Social está ligado al grado de Participación Política que presenta la Comunidad Rural participante.

The main objective of this research is to determine the correlation between Social Welfare and Political Participation in adults belonging to a Rural Community from Minga Guazu, Alto Parana. The sample consisted of 70 adults, regardless of sex. We used a descriptive and correlational design. Data analysis was performed using the linear correlation coefficient R Pearson, obtaining a positive relationship between the two scales related. We conclude that Social Welfare is linked to the grades of political participation presented by the participant Rural Community.

Morfometría tomográfica del foramen magno y su relación con el sexo y la etnia mapuche / Tomographic morphometry of the foramen magnum and its relation to sex and Mapuche ethnicity

Introducción: El foramen magno es una estructura anatomoquirúrgica importante en síndromes compresivos del sistema nervioso central, en que se ven comprometidas la función neuronal y circulatoria. Objetivo: Determinar los valores morfométricos del foramen magno en tomografías computarizadas y su relación con el sexo y la etnia mapuche. Material y Método: Estudio descriptivo tipo corte transversal realizando muestreo no probabilístico por conveniencia de 100 tomografías computarizadas cerebrales (TC), realizadas en el Hospital Hernán Henríquez Aravena en 2010 e informadas como “normal” por médico especialista. Fueron seleccionados 50 hombres y 50 mujeres, integrándose dentro de cada grupo 25 TC de sujetos que presentaran apellidos de la etnia mapuche. Se midió diámetro transverso, diámetro anteroposterior y área, además de determinar la forma. Análisis estadístico con Stata 10,1, estudiándose diferencias con t de Student y considerándose un p<0,05 como significativo estadísticamente. Todos los sujetos permanecieron bajo anonimato en las bases de datos construidas. Resultados: Entre hombres y mujeres existen diferencias estadísticamente significativas en todas las mediciones, siendo mayores en el sexo masculino. Existen además diferencias estadísticamente significativas en la medición del área entre sujetos mapuches y no mapuches, siendo menores en los primeros. La forma predominante fue la oval. Discusión: Las diferentes mediciones entre sexos son concordantes con la literatura. Existen diferencias en las medidas de forámenes magnos de sujetos mapuches y no mapuches, pudiendo servir estos datos para nuevos estudios en el área.

Introduction: The foramen magnum is an important surgical anatomical structure in the compression syndromes of the central nervous system, which are compromised neuronal function and circulation. Objective: To determine the morphometric values of the foramen magnum on CT and its relation to sex and Mapuche ethnicity. Material and Method: Descriptive cross-sectional type made by non-probabilistic convenience sampling of 100 brain CT scans (CT) performed at the Hospital Hernán Henríquez Aravena in 2010 reported as"normal" for radiologists. Were selected 50 men and 50 women, integrating within each group 25 TC of subjects with surnames belonging to the Mapuche ethnicity. We measured the transverse diameter, anteroposterior diameter and area, in addition to determining the shape. The data was analyzed using Stata 10.1, comparing different variables with t-test, considering statistically significant a p value < 0.05. All subjects remained under anonymity in the built databases. Results: We found statistically significant differences in all measurements between men and women, being higher in males. There are also significant differences in the measurement of the area between Mapuche and non Mapuche patients, being lower in the first ones. The oval shape was predominant. Discussion: The different measurements between sexes are consistent with the literature. There are differences in measures of foramen magnum of Mapuche and non Mapuche patients and can serve as data for further studies in the area.

Compromiso vesical en síndrome de Guillain-Barré: a propósito de un caso / Bladder involvement in Guillain-Barre syndrome: a case study

Introducción: El Síndrome de Guillain-Barré (SGB) es una enfermedad autoinmune caracterizada por debilidad muscular, arreflexia y disociación albúmino-citológica en líquido cerebroespinal, cuya incidencia clásica a nivel internacional suele uniformarse alrededor de 0,6 a 4 casos por 100.000 al año. Presentación del caso: Paciente de 45 años, sexo femenino, quien ingresó al Servicio de Urgencia del Hospital de Temuco derivada desde Lonquimay, por debilidad progresiva de las cuatro extremidades. En Lonquimay la paciente requirió sonda vesical por retención urinaria. Es diagnosticada con SGB, hospitalizándose en Unidad de Cuidados Intensivos, requiriendo ventilación asistida y tratada mediante plasmaféresis, presentando neumonía como complicación relacionada a la ventilación mecánica y recuperando íntegramente función vesical. Discusión: El compromiso vesical no es descrito como un factor importante en el diagnóstico, siendo controversial aquella afirmación por varios autores.

Introduction: Guillain-Barre syndrome (GBS) is an autoimmune disease characterized by muscle weakness, areflexia and albumin-cytological dissociation in cerebrospinal fluid, the incidence has been reported to be relatively uniform between 0.6 to 4 cases per 100.000 per year. Case report: Patient of 45 years old, female, admitted to the emergency department of Hospital de Temuco derived from Lonquimay by progressive weakness of four extremities. In Lonquimay the patient required bladder catheterization for urinary retention. It was diagnosed with GBS, hospitalized in intensive care unit, requiring assisted ventilation and treated with plasmapheresis, developing pneumonia as a complication related to mechanical ventilation and fully recovered bladder function. Discussion: The bladder involvement is not described as an important factor in diagnosis and remains controversial this statement by several authors.

Accumulation of BNP7787 in human renal proximal tubule cells.

BNP7787, an investigational drug undergoing global Phase III development, appears to have potential advantages over other cytoprotective compounds that have been evaluated for preventing and mitigating cisplatin-induced nephrotoxicity. Herein, we characterized the in vitro accumulation of BNP7787 in human renal proximal tubule cells (HK-2) in which cisplatin is known to be taken up and accumulate. HK-2 cells were incubated with pharmacological concentrations of BNP7787 for varying times. Temperature-dependent accumulation of BNP7787 in cells was observed and the BNP7787-derived metabolite, mesna, formed intracellularly was directly monitored. The peak level of BNP7787-derived mesna measured in HK-2 cells was approximately 0.6 nmol/10(6) cells; this is pharmacologically similar to reported platinum concentrations in kidney cells and may be sufficient to afford nephroprotection. Therefore, in addition to previously suggested glomerular filtration, the cellular accumulation of BNP7787 by HK-2 cells is a plausible newly identified mechanism by which BNP7787 may accumulate in renal tubular cells, where it can exert its pharmacological effects to protect against cisplatin-induced nephrotoxicity by direct covalent conjugation of mesna with cisplatin, or by the formation of BNP7787-derived mesna-disulfide heteroconjugates that exert nephroprotective effects by inhibition of the key toxification enzyme targets γ-glutamyltranspeptidase and aminopeptidase N.

Mechanistic study of BNP7787-mediated cisplatin nephroprotection: modulation of human aminopeptidase N.

PURPOSE: Previous studies from our laboratory have identified a role for gamma-glutamyl transpeptidase (GGT) in BNP7787 (disodium 2,2'-dithio-bis ethane sulfonate, dimesna, Tavocept™)-mediated cisplatin nephroprotection. Dekant has proposed that gamma-glutamyl transpeptidase (GGT), aminopeptidase N (APN) and cysteine-conjugate-ß-lyase (CCBL) comprise a multi-enzyme pathway that acts on xenobiotic-glutathione conjugates converting them to nephrotoxic metabolites. We report modulation of APN activity within this pathway by BNP7787-derived mesna-disulfide heteroconjugates. METHODS: A fluorimetric assay was used to determine the effect of BNP7787, BNP7787-derived mesna-disulfide heteroconjugates, and the BNP7787 metabolite, mesna (sodium 2-mercaptoethane sulfonate), on the initial velocity and overall progress curve of the human APN reaction in vitro. RESULTS: Neither BNP7787 nor mesna-cysteinyl-glutamate inhibited human APN. Select BNP7787-derived mesna-disulfide heteroconjugates (mesna-cysteine, mesna-glutathione, mesna-cysteinyl-glycine) and high concentrations of mesna inhibited APN activity. Allosteric effects on the enzyme progress curve outside of the linear initial velocity region were observed for mesna-cysteinyl-glycine, mesna-glutathione and mesna-cysteinyl-glutamate and appeared to be a function of having both mesna and di- or tri-peptide functionalities in one molecule. In situ-generated mesna-cisplatin conjugates were not a substrate for human APN. CONCLUSIONS: BNP7787-mediated prevention or mitigation of cisplatin-induced nephrotoxicity may involve APN inhibition by certain BNP7787-derived mesna-disulfide heteroconjugates and appears correlated to the presence of a glycinate moiety and/or an anionic group. Two general mechanisms for BNP7787-mediated nephroprotection of cisplatin-induced nephrotoxicity involving the GGT, APN and CCBL nephrotoxigenic pathway are proposed which acting in a concerted and/or synergistic manner, and thereby prevent or mitigate cisplatin-induced renal toxicity.

Spectroscopic characterization of N-doped single-walled carbon nanotube strands: an X-ray photoelectron spectroscopy and Raman study.

We have studied in detail the carbon and nitrogen bonding environments in nitrogen-doped single-walled carbon nanotubes (SWCNTs). The samples consisting of long strands of N-doped SWCNTs were synthesized using an aerosol assisted chemical vapor deposition method involving benzylamine-ethanol-ferrocene solutions. The studied samples were produced using different benzylamine concentrations in the solutions, and exhibited a maximum concentration of ca. 0.3%at of N, determined by X-ray photoelectron spectroscopy (XPS). In general, we observed that the ratio between substitutional nitrogen and the pyridine-like bonded nitrogen varied upon the precursor composition. Moreover, we have observed that the sp2-like substitutional configuration of the C-N bond does not exceed the 50% of the total N atomic incorporation. In addition, we have characterized all these samples using Raman spectroscopy and electron microscopy.

Wheat starch digestion rate affects broiler performance.

Two experiments were conducted to determine the differences in starch digestion rate (KDS) among wheats from different cultivars and origins and to verify if chickens would benefit from a certain digestion rate of starch. In the first experiment, 192 chickens (21 d) were assigned to 4 diets containing 55% of each wheat sample (3 cultivars, one of them from 2 origins). Starch and protein digestion were calculated from the remaining starch and protein in 4 segments of the small intestine and in excreta, using chromic oxide as a marker. Mean retention time was measured in each segment, which enabled calculations of digestion rates. In the second experiment, 2,600 chickens were assigned to 5 isoenergetic and isonitrogenous diets (with KDS from 1.80 to 2.56 h(-1)) and growth performance was determined (1 to 34 d). In 3 treatments, dietary starch was provided each by the wheat cultivars (same origin), whereas in the other 2 treatments, 25 and 50% of the wheat starch with the highest KDS was substituted by pea starch. Clostridium perfringens and Lactobacillus in the cecal chyme and glucose in the blood (glycemic index) were measured in broilers at d 19 and 25, respectively. Starch was gradually digested along the small intestine, mainly in the jejunum (48.5 and 80.4% at proximal and distal jejunum) where the largest differences among wheat samples were found. Starch digestion rate varied with origin (from 1.96 to 2.56 h(-1)) and cultivar (from 2.17 to 2.56 h(-1)). Crude protein digestion rate (average 2.21 h(-1)) was not affected by either cultivar or origin. Broiler growth and feed conversion ratio improved in a quadratic way with KDS. The maximum broiler performance was observed with KDS around 2.2 h(-1). Blood glucose response (glycemic index) was not affected by KDS; therefore, it cannot be used to predict broiler performance. In conclusion, the rate of starch digestion varies among wheats, depending on both genetic and environmental conditions of the grain, and affects broiler performance.

Wheat starch digestion rate in broiler chickens is affected by cultivar but not by wheat crop nitrogen fertilisation.

1. A study was set up to investigate the influence of wheat cultivar and wheat crop nitrogen (N) fertilisation on starch (ST) digestion rate in broiler chickens. A total of 288 broiler chickens were used in a 3 x 2 factorial design with diets based on three varieties of wheat (Apache, Caphorn and Charger), each grown at two N application rates (40 and 170 kg of N/ha). 2. Starch digestion rate was determined by measuring the remaining starch and the mean retention time (MRT) in 4 segments of the small intestine (proximal and distal jejunum and proximal and distal ileum) and in excreta, using chromic oxide as a marker. 3. Varietal differences in starch content (714-746 g starch/kg DM) were smaller than differences caused by crop N fertilisation (705-755 g starch/kg DM). Nitrogen application increased wheat crude protein (CP) content from 94 to 130 g/kg DM. 4. The majority of the ST in all diets was digested by the time the digesta reached the distal ileum (average 0.84 in the distal jejunum and 0.96 in the proximal ileum). 5. Starch digestion differed among wheat cultivars in the proximal jejunum (from 0.43 to 0.57, P < 0.001). Afterwards no differences due to wheat cultivar or N fertilisation were found. 6. Starch digestion rate varied among wheat cultivars (from 2.45 to 3.28 h(-1), P < 0.001), but did not vary with N fertilisation, whereas dietary CP digestion rate was not affected by wheat cultivar or N fertilisation level. The digestion rate of ST was faster than that of CP (average 2.78 vs. 1.53 h(-1)). 7. The current study suggests that wheat cultivars can be classified on their rate of ST digestion independently of the N fertilisation applied to the crop during growth.