Dose-response relationship between toothpaste soluble fluoride absorbed in the gastrointestinal tract and saliva fluoride secretion

Aim: This study aimed to evaluate if there is a dose-response relationship between toothpaste chemically soluble fluoride absorbed in the gastrointestinal tract and fluoride secreted by saliva, giving support to the use of saliva as surrogate for plasma fluoride. Methods: A 4-phase single blind study was conducted, in which 10 participants were subjected in each phase to one of the assigned treatment groups: group I: fresh sample of a Na2FPO3/CaCO3-based toothpaste with 1,334 µg F/g of total soluble fluoride (TSF) and groups II­IV: aged samples of this toothpaste presenting TSF concentrations of 1,128, 808, and 687 µg F/g, respectively. In all phases, the participants ingested an amount of toothpaste equivalent to 70.0 µg F/Kg body weight, as total fluoride (TF). Saliva and blood samples were collected before (baseline) and up to 180 min after toothpaste ingestion as indicator of fluoride bioavailability. F concentration in saliva and blood plasma was determined with a fluoride ion-specific electrode. The areas under the curve (AUC) of F concentration versus time (AUC = ng F/mL × min) and the peaks of fluoride concentration (Cmax) in saliva and plasma were calculated. Results: A significant correlation between mg of TSF ingested and the AUC (r=0.47; p<0.01), and Cmax (r=0.59; p<0.01) in saliva was found; for TF, the correlation was not significant (p>0.05). In addition, the correlations between plasma and saliva fluoride concentrations were statistically significant for AUC (r=0.55; p<0.01) as for Cmax (r=0.68; p<0.01). Conclusion: The findings support that saliva can be used as a systemic biomarker of bioavailable fluoride present in Na2FPO3/CaCO3-based toothpaste

Cápsulas de polvo de arándano como propuesta nutracéutica para mejorar la bioaccesibilidad de compuestos fenólicos / Blueberry Powder capsules as a nutraceutical proposal to improve bioaccessibility of phenolic compounds. Introduction

El arándano (Vaccinium corymbosum L.) posee un alto contenido de compuestos fenólicos los cuales han sido estudiados principalmente por su actividad antioxidante, antiobesogénica, antiinflamatoria, entre otras. Objetivo. Evaluar el efecto de la digestión gastrointestinal in vitro sobre la bioaccesibilidad de compuestos fenólicos y actividad antioxidante de una formulación nutracéutica de arándano (cápsula), comparado con arándano fresco y polvo. Materiales y métodos. Se obtuvieron extractos metanólicos de muestras de arándano fresco y liofilizado y se determinó su contenido de fenoles, flavonoides y antocianinas totales, así como también actividad antioxidante. Se llevó a cabo un ensayo de simulación de digestión gastrointestinal para evaluar la bioaccesibilidad de los compuestos fenólicos presentes en las muestras. Resultados. Los resultados mostraron que la digestión gástrica de arándano en polvo y en cápsula promovió una mayor bioaccesibilidad de fenoles (42% y 40%), flavonoides (52% y 33%) y antocianinas (45% y 40%) comparado con digestos de arándano fresco. Posterior a la digestión intestinal, la bioaccesibilidad de fenoles (63%) y flavonoides (67%) fue mayor en la cápsula de arándano comparada con su contraparte arándano en polvo. Las condiciones de digestión intestinal afectaron negativamente la bioaccesibilidad de las antocianinas independientemente del tipo de muestra evaluada. Conclusión. Las condiciones de digestión gástrica promueven una mayor estabilidad de los compuestos fenólicos en arándano en polvo y en cápsula lo que pudiera ser relevante para el mantenimiento de un ambiente antioxidante a este nivel. Las condiciones de digestión intestinal afectaron de manera particular a los compuestos fenólicos de arándano fresco y polvo, pero no a la cápsula, lo que puede sugerir que el encapsulamiento protegió de las condiciones alcalinas a los fenoles presentes. Se sugieren estudios posteriores sobre absorción in vitro de los componentes remanentes en intestino y sus posibles efectos sobre biomarcadores de estrés oxidativo en modelos in vivo(AU)

Blueberry (Vaccinium corymbosum L.) has a high content of phenolic compounds which have been studied mainly for their antioxidant, antiobesogenic, anti-inflammatory activity, among others. Objetive. The objective of the present study was to evaluate the effect of in vitro gastrointestinal digestion on the bioaccessibility of phenolic compounds and antioxidant activity of a nutraceutical formulation of blueberry (capsule), compared to fresh and powder blueberry. Materials and methods. Methanolic extracts of fresh and lyophilized blueberry were obtained and determined its total phenols, flavonoids, anthocyanins content, as well as antioxidant activity. A gastrointestinal digestion simulation test also was carried out to assess the bioaccessibility of the phenolic compounds found in samples. Results. The results showed that gastric digestion of powder and capsule blueberry promoted greater bioaccessibility of phenols (42% and 40%), flavonoids (52% and 33%) and anthocyanins (45% and 40%), compared to fresh blueberry digests. After intestinal digestion, the bioaccessibility of phenols (63%) and flavonoids (67%) was higher in the blueberry capsule compared to its powdered blueberry counterpart. The intestinal digestion conditions negatively affected the bioaccessibility of anthocyanins regardless of the type of sample evaluated. Conclusion. Gastric digestion conditions promote greater stability of phenolic compounds in powdered and capsule blueberries, which could be relevant for the maintenance of an antioxidant environment at this level. The intestinal digestion conditions particularly affected the phenolic compounds of fresh and lyophilized blueberry, but not the capsule, which may suggest that encapsulation protected the phenols present from alkaline conditions. Further studies on in vitro absorption of the remaining components in the intestine and their possible effects on oxidative stress biomarkers in in vivo models are suggested(AU)

Mature Solid Teratoma of the Retroperitoneum Presenting as Sigmoid Colon Polyp with Lower Gastrointestinal Bleeding: A Case Report

Mature colonic teratomas are rare tumors and no case, to the best of our knowledge, has been reported from the African continent. In addition, some pedunculated teratomas in the colon have been treated by endoscopic polypectomy and classified as primary teratoma of the colon. We report a case of a distinct intra sigmoid pedunculated teratoma originating from the retroperitoneum of a 4-year-old African girl and we highlight the potential for misclassification of primary origin of endoscopically removed polypoid teratomas in the colon. CASE PRESENTATION: A 4-year-old black African female child who presented with abdominal pain and hematochezia. On clinical assessment, she was found to be anaemic and to have a sigmoid colon mass. At surgery, there was a mobile mass within the lumen of sigmoid colon and the mass was fixed to the retroperitoneum by a stalk of tissue. Pathologist's review of the resected sigmoid segment showed a pedunculated intra-sigmoid mass with the stalk traversing the wall of the colon. The mass was histologically proven a mature solid teratoma. CONCLUSION: This, to the best of our knowledge, is the first report of intra sigmoid teratoma from the African continent. It highlights the potential for misclassification of endoscopically resected colonic teratomas

Nanostructured lipid carrier containing hydroxymethylnitrofurazone: preparation, characterization and in vitro and in vivo evaluation of leishmanicidal activity / Carreador lipídico nanoestruturado contendo hidroximetilnitrofural: preparação, caracterização físico-química e avaliação in vitro e in vivo da atividade leishmanicida

Leishmaniasis, a neglected tropical disease (NTD), is a set of diseases caused by obligatory parasitic protozoa of the genus Leishmania. And it has cutaneous and visceral eishmaniasis as its main forms. Treatment includes pentavalent antimonials. These drugs have several disadvantages, such as the need for parenteral administration, use of high dosages, long duration of treatment, severe toxicity, resistance and variable efficacy. The candidate for hydroxymethylnitrofural drug (NFOH), a prodrug derived from nitrofural, showed high activity in cell cultures infected with Trypanosoma cruzi and less toxicity when compared to nitrofural. Due to its low solubility in water and reduced bioavailability, NFOH has failed the in vivo efficacy tests. Nanostructured drug delivery systems have the potential to overcome these challenges due to their evident advantages: greater therapeutic efficacy, less toxicity, modified drug release and increased gastrointestinal absorption of drugs with low water solubility. The objective of this project will be the preparation and evaluation of the physicochemical characteristics of a nanostructured lipid carrier containing hydroxymethylnitrofural (NLC-NFOH). The NFOH showed the highest solubility in Miglyol® 840 among the tested liquid lipids. For solid lipids, Gelucire® 50/13 and Precirol® ATO5 proved to be more suitable for the solubilization of NFOH. The optimized NLC-NFOH consisted of these three lipids. These lipids were selected using a quick Technobis Crystal 16TM methodology, microscopy and DSC. Different lipid selection tools provided scientific knowledge relevant to the development of NLC. The NLC-NFOH had an average z of 198.6 ± 5.4 nm, a PDI of 0.11 ± 0.01 and a zeta potential of -13.7 ± 0.7 mV. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally. The development of a sensitive bioanalytical method using HPLC and evaluation of some analytical figures of merit for the validation allowed the quantification of NFOH and NF. The bioanalytical method for analysis of NFOH and NF use Zorbax SB-C18, 5µm, (4.6x250mm) HPLC column. The mobile phase was consisted of acetonitrile:water (20:80 v/v) with flow rate of 1.2 ml/min, at UV detection of 370 nm. The linearity of NFOH and NF was found in the range 0.0253.0 µg/ml with a correlation coefficient of r > 0.98. The precision was 2.44 to 13.77% for NFOH and 2.61 to 18.42%; the accuracy was 2.66 to 14.28% for NFOH and 2.09 to 19.06% for NF. The method showed to be suitable for effectively evaluation of NFOH is serum. NLC-NFOH (2.8 mg/kg) was administered to animals by gavage, and the blocking flow of the chylomicrons model was performed with an intraperitoneal injection of cycloheximide. The presence of NFOH in serum was evaluated with and without cycloheximide. The cytotoxicity assay of NLC-NFOH and blank-NLC showed more than 90% viable cells at the maximum concentration used (2560 µM). NFOH and NF were detected at 1h after the gavage of DMSO-NFOH or NLC-NFOH, without the pretreatment with cycloheximide. The concentration found for DMSO-NFOH and NLC-NFOH were 0.0316 and 0.0291 µg/mL, respectively. The NLC presented the NFOH absorption by the lymphatic system, demonstrated by blocking chylomicrons flow

A leishmaniose, uma doença tropical negligenciada (DTN), é um conjunto de doenças causadas por protozoários parasitas obrigatórios do gênero Leishmania. E tem como formas principais a leishmaniose cutânea e visceral. O tratamento inclui antimoniais pentavalentes. Esses fármacos apresentam várias desvantagens, como necessidade de administração parenteral, uso de altas dosagens, longa duração do tratamento, toxicidade grave, resistência e eficácia variável. O candidato ao fármaco hidroximetilnitrofural (NFOH), um pró-fármaco derivado do nitrofural, apresentou alta atividade em culturas de células infectadas pelo Trypanosoma cruzi e menor toxicidade quando comparado ao nitrofural. Devido à sua baixa solubilidade em água e biodisponibilidade reduzida, o NFOH falhou nos testes de eficácia in vivo. Os sistemas nanoestruturados de liberação de fármacos têm potencial para superar esses desafios devido às suas vantagens evidentes: maior eficácia terapêutica, menor toxicidade, liberação modificada do fármaco e aumento da absorção gastrointestinal de fármacos com baixa solubilidade em água. O objetivo deste projeto será a preparação e avaliação das características físico-químicas de um carreador lipídico nanoestruturado contendo hidroximetilnitrofural (NLC-NFOH). O NFOH apresentou a maior solubilidade no Miglyol® 840 entre os lipídios líquidos testados. Para lipídios sólidos, Gelucire® 50/13 e Precirol® ATO5 se mostraram mais adequados para a solubilização de NFOH. O NLC-NFOH otimizado consistiu desses três lipídios. Esses lipídios foram selecionados usando Technobis Crystal 16TM, microscopia e DSC. Diferentes ferramentas de seleção de lipídios forneceram conhecimento científico relevante para o desenvolvimento de NLC. O NLC-NFOH teve z-average de 198,6 ± 5,4 nm, PDI de 0,11 ± 0,01 e potencial zeta de -13,7 ± 0,7 mV. Este estudo permitiu o desenvolvimento por abordagem de Design Space do primeiro NLC-NFOH com potencial para tratar a leishmaniose por via oral. O desenvolvimento de um VIII método bioanalítico sensível utilizando HPLC e a avaliação de algumas figuras analíticas de mérito para a validação permitiram a quantificação de NFOH e NF em soro. O método bioanalítico para análise de NFOH e NF usou coluna de HPLC Zorbax SB-C18, 5 µm, (4,6 x 250 mm). A fase móvel foi constituída por acetonitrila: água (20:80 v / v) com vazão de 1,2 ml / min, com detecção no UV de 370 nm. A linearidade de NFOH e NF foi encontrada na faixa de 0,0253,0 µg / ml com um coeficiente de correlação de r> 0,98. A precisão foi de 2,44 a 13,77% para NFOH e 2,61 a 18,42%; a precisão foi de 2,66 a 14,28% para NFOH e 2,09 a 19,06% para NF. O método mostrou-se adequado para avaliação efetiva do NFOH no soro. NLC-NFOH (2,8 mg / kg) foi administrado aos animais por gavagem, e o modelo de bloqueio do fluxo de quilomícrons foi realizado com injeção intraperitoneal de cicloheximida. A presença de NFOH no soro foi avaliada com e sem cicloheximida. O ensaio de citotoxicidade de NLC-NFOH e brancoNLC mostrou mais de 90% de células viáveis na concentração máxima utilizada (2560 µM). NFOH e NF foram detectados 1h após a gavagem de DMSO-NFOH ou NLC-NFOH, sem o pré-tratamento com cicloheximida. As concentrações encontradas para DMSO-NFOH e NLC-NFOH foram 0,0316 e 0,0291 µg / mL, respectivamente. O NLC apresentou a absorção do NFOH pelo sistema linfático, demonstrada pelo bloqueio do fluxo dos quilomícrons

Therapeutic failure with itraconazole in sporotrichosis due to bariatric surgery

Abstract Sporotrichosis is a deep mycosis of subacute or chronic evolution, caused by the dimorphic fungus of the genus Sporothrix. The treatment is carried out with antifungal orally or intravenously. Therapeutic success can be affected by several factors, such as altered gastrointestinal physiology by surgery. More and more patients are submitted to bariatric surgeries and the literature for the alterations of the absorption of medications in this context is very scarce. We intend to contribute to a better understanding with this case report of cutaneous-lymphatic sporotrichosis in a patient after bariatric surgery without response to itraconazole treatment, even at high doses.

Psychodynamic Study about Reflux and Colic During the First Year of Life / Estudo Psicodinâmico dos Sintomas Refluxo e Cólica no Primeiro Ano de Vida / Estudio Psicodinámico de los Síntomas de Reflujo y Cólico en el Primer Año de Vida

Abstract The aim of this study was to analyze the psychodynamics of three mother-infant pairs with reflux diagnosis and two with colic diagnosis and their possible relation to the referred psychosomatic disorders. Qualitative exploratory study in which the sample was composed after signing the informed consent form. Instruments: semi-directed interview, seven boards of the Thematic Apperception Test and Naturalistic Observation. Content analysis of the interviews and TAT boards was performed and the way the mother perceived the productions of the baby was considered from naturalistic observation. These analyses supported psychodynamic interpretations of the functioning of the dyads studied. As main results, the reflux group highlights the need for maternal support and the presence of maternal ambivalence. In mother-infant pairs with colic, there is anxiety regarding their own ability to care for their child. In both groups, there is environmental influence on the way mothers feel about sufficiently good mothering.

Resumo O objetivo deste estudo foi analisar a psicodinâmica de três pares mãe-bebê com diagnóstico de refluxo e dois com diagnóstico de cólica e sua possível relação com as referidas desordens psicossomáticas. Trata-se de estudo qualitativo e exploratório cuja a amostra foi composta após assinatura do termo de consentimento. Instrumentos: entrevista semi-dirigida, sete pranchas do Teste de Apercepção Temática (TAT) e Observação Naturalista. Procedeu-se análise de conteúdo das entrevistas e das pranchas do TAT e, da observação naturalista, valorizou-se principalmente a maneira como a mãe percebeu as produções do bebê. Estas análises respaldaram interpretações psicodinâmicas do funcionamento das díades estudadas. Como principais resultados, destaca-se no grupo refluxo a necessidade de apoio para maternar e presença de ambivalência materna. Já nos pares mães-bebês com cólica, há ansiedade frente à própria capacidade de cuidar do filho. Nos dois grupos, há influência ambiental na maneira como as mães se sentem no exercício da maternagem suficientemente boa.

Resumen El objetivo de este estudio fue analizar la psicodinámica de 3 parejas madre-bebé con diagnóstico de reflujo y 2 con cólico y la posible relación de estos síntomas con trastornos psicosomáticos. El estudio es cualitativo y exploratorio. La muestra se compuso después de que los participantes firmaron el formulario de consentimiento. Instrumentos: entrevista semidirigida, 7 láminas del Test de Apercepción Temática y observación naturalista. Se realizó un análisis de contenido de las entrevistas y de las láminas del TAT y, a partir de la observación naturalista, se valoró la forma en que la madre percibió las producciones del bebé. Estos análisis respaldaron interpretaciones psicodinámicas del funcionamiento de las díadas estudiadas. Como resultados principales, en el grupo reflujo se destacan la necesidad de apoyo a la madre y la presencia de ambivalencia materna. En las parejas madre-bebé con cólico, se percibe ansiedad con respecto a la capacidad para cuidar al niño. En ambos grupos, hubo influencia ambiental en los sentimientos de las madres sobre el buen ejercicio de la maternidad.

Preclinical studies of hydroalcoholic extract of Calea uniflora Less / Estudios preclínicos de extracto hidroalcohólico de Calea uniflora Less

Calea uniflora Less known popularly as Arnica in Brazil, is a native plant from Brazil, popular used by coastal populations from south of Santa Catarina. The purpose of this study was to verify the safety profile in of hydroalcoholic extract of C. uniflora in florescences.The hydroalcoholic extract of C. uniflora in florescences was evaluated for its acute and sub-acute toxicity. Acute topical toxicity was performed using the methodology of guideline 402 from OECD. Acute oral toxicity was performed using the methodology of guideline 423 from OECD and sub-acute toxicity was performed using the methodology adapted of guideline 407 from OECD. The single dose for oral or topical administration of C. uniflora showed DL50> 5000 mg/kg b.w. The sub-acute treatment induced animal death in groups, which was administered extract in the doses 100, 250, 500 and 1000 mg/kg. The main signs of toxicity observed were respiratory difficulty, increase in lung weigh, lung damage and muscular relation. The topical or oral administration of C. uniflora extract in short period did not caused toxicological effects in animals, however, when administered for a longer period and in concentrations of 250, 500 and 1000 mg/kg (oral.) caused lung damage and even the death of the animal.

Calea uniflora Less conocida popularmente como Arnica en Brasil, es una planta nativa de Brasil, popularmente utilizada por poblaciones costeras del sur de Santa Catarina. El objetivo de este estudio fue verificar el perfil de seguridad del extracto hidroalcoólico de inflorescencias de C. uniflora. El extracto hidroalcoólico de inflorescencias de C. uniflora fue evaluado en cuanto a su toxicidad aguda y subaguda. La toxicidad tópica aguda se realizó utilizando la metodología de la directriz 402 de la OECD. La toxicidad oral aguda fue realizada usando la metodología de la directriz 423 de la OECD y la toxicidad subaguda fue realizada usando la metodología adaptada de la directriz 407 de la OECD. La dosis única para administración oral o tópica de C. uniflora mostro DL50> 5000 mg/kg. El tratamiento subagudo indujo la muerte de animales en grupos a los que se administró extracto en las dosis de 100, 250, 500 y 1000 mg/kg. Los principales signos de toxicidad observados fueron dificultad respiratoria, aumento del peso del pulmón, daño pulmonar y relación muscular. La administración tópica oral del extracto de C. uniflora a corto plazo no causó efectos toxicológicos en los animales, mientras que, cuando se administró por un período mayor y en las concentraciones de 250, 500 y 1000 mg/kg (oral) causaron danos en los pulmones y hasta la muerte del animal.

A Novel High-Visibility Radiopaque Tantalum Marker for Biliary Self-Expandable Metal Stents

BACKGROUND/AIMS: Radiopaque metal markers are required to improve X-ray absorption by self-expandable metal stents (SEMSs) to enable precise stent placement. A new tantalum radiopaque marker was recently developed using an ultrasonic spray technique. The aim of the present study was to evaluate the safety and visibility of tantalum markers. METHODS: A total of three beagle dogs were used for a gastrointestinal tract absorption test. Five tantalum markers were placed in the stomach of each dog endoscopically. Excreted tantalum markers were collected, and their weights were compared to the original weights. In radiopacity tests, marker radiopacities on X-ray images were quantified using ImageJ software and compared with those of commercially available metal markers. Finally, the radiographic images of six patients who underwent biliary SEMS placement using tantalum marker Nitinol SEMSs (n=3) or gold marker Nitinol SEMSs (n=3) were compared with respect to marker brightness on fluoroscopic images. RESULTS: Absorption testing showed that the marker structures and weights were unaffected. Radiopacity tests showed that the mean brightness and total brightness scores were greater for tantalum markers (226.22 and 757, respectively) than for gold (A, 209 and 355, respectively; B, 204.96 and 394, respectively; C, 194.34 and 281, respectively) or platinum markers (D, 203.6 and 98, respectively). On fluoroscopic images, tantalum markers had higher brightness and total brightness scores (41.47 and 497.67, respectively) in human bile ducts than gold markers (28.37 and 227, respectively). CONCLUSIONS: Tantalum markers were found to be more visible than other commercially available markers in X-ray images and to be resistant to gastrointestinal absorption.

Isolated branched-chain amino acid intake and muscle protein synthesis in humans: a biochemical review / Consumo isolado de aminoácidos de cadeia ramificada e síntese de proteína muscular em humanos: uma revisão bioquímica

ABSTRACT Alongside a proper diet, ergogenic aids with potential direct and/or indirect physical performance enhancing effects are sought after for improved adaptation to physical training. Nutritional ergogenics include diet composition changes and/or dietary supplementation. Branched-chain amino acids valine, leucine and isoleucine are widely popular among products with ergogenic claims. Their major marketing appeal derives from allegations that branched-chain amino acids intake combined with resistance physical exercise stimulates muscle protein synthesis. Evidence supporting the efficacy of branched-chain amino acids alone for muscle hypertrophy in humans is somewhat equivocal. This brief review describes physiological and biochemical mechanisms underpinning the effects of complete protein source and branched-chain amino acid intake on skeletal muscle growth in the postabsorptive and post-exercise state. Evidence in favor of or against potential anabolic effects of isolated branched-chain amino acid intake on muscle protein synthesis in humans is also examined.

RESUMO No treinamento físico, buscam-se, além de uma dieta adequada, recursos ergogênicos que possam maximizar direta e/ou indiretamente o desempenho físico. Entre as categorias de recursos ergogênicos, o nutricional compreende a modulação da composição dietética e/ou uso de suplementação. A comercialização dos suplementos de aminoácidos de cadeia ramificada valina, leucina e isoleucina possui muita popularidade entre aqueles com alegação ergogênica. O principal marketing está na afirmação de que o consumo isolado de aminoácidos de cadeia ramificada associado ao exercício físico resistido estimula a síntese de proteína muscular. As evidências da eficácia da ingestão isolada de aminoácidos de cadeia ramificada para a hipertrofia muscular em humanos parecem equivocadas. Nesta breve revisão, apresentamos a compreensão fisiológica e bioquímica de como a ingestão de uma fonte completa de proteína e de aminoácidos de cadeia ramificada afeta o crescimento do músculo esquelético no estado pós-absortivo e pós-exercício. Mostramos também as evidências que suportam ou não a afirmação dos potenciais efeitos anabólicos na síntese de proteína muscular dos aminoácidos de cadeia ramificada quando consumidos isoladamente em humanos.

Estudio comparativo de la absorción neta de calcio de dos formulaciones distintas de carbonato de calcio en mujeres posmenopáusicas / Comparative study of net calcium absorption of two different pharma¬ceutical formulations of calcium carbonate in posmenopausal women

La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)

Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)

A influência da água mineral sobre a absorção dos bisfosfonatos orais / The influence of mineral water on the absorption of bisphosphonates

Introdução: as doenças osteometabólicas ocorrem quando a reabsorção do osso excede a formação. Os bisfosfonatos são fármacos antirreabsortivos usados no tratamento e prevenção da perda de massa óssea decorrente da osteoporose, doença de Paget e outras condições. Os bisfosfonatos são considerados tratamento de primeira escolha na prevenção da perda de massa óssea e do aumento da susceptibilidade a fraturas, associadas ao envelhecimento. Os bisfosfonatos orais são pouco absorvidos pelo trato gastrointestinal. Devido à sua alta tendência em formar complexos com o cálcio, as bulas advertem que os mesmos não devem ser ingeridos com água mineral, que pode conter altos teores de cálcio. Os bisfosfonatos orais alendronato e risedronato integram os Protocolos Clínicos e Diretrizes Terapêuticas (PCDT) do SUS. Porém, estes não mencionam a necessidade de evitar ingerir os comprimidos com água mineral. O efeito protetor dos bisfosfonatos depende do uso correto. Objetivo: conduzir uma revisão dos estudos sobre a influência da água mineral na absorção dos bisfosfonatos. Resultados e Discussão: o cálcio e os bisfosfonatos formam complexos relativamente insolúveis de alto peso molecular em pH fisiológico. Quanto maior a concen tração de cálcio da água mineral, menor a absorção desses fármacos. Os complexos formados podem ser mais citotóxicos do que as formas livres. A filtração da água pode remover em média 89% do cálcio nela presente. Conclusão: bisfosfonatos devem ser ingeridos preferencialmente com água filtrada. A ingestão com água mineral contendo altos teores de cálcio não é recomendada.

Introduction: bone diseases occur when bone resorption exceeds bone formation. Bisphosphonates are bone antiresorptive agents used in the treatment and prevention of bone loss due to osteoporosis, Paget's disease and other conditions. Bisphosphonates are used as first-line medications for the prevention of bone loss and susceptibility to fractures associated with aging. Oral bisphosphonates are only poorly absorbed from the gastrointestinal tract. Because of their high tendency to complex with calcium, the informational packages state that they should not be ingested with mineral water, which may contain high level of calcium. The oral bisphosphonates alendronate and risedronate are included in the Clinical Protocols and Therapeutic Guidelines (PCDT) of the Brazilian Health System (SUS). However, PCDT do not refer to the need to avoid the intake of tablets with mineral water. The protective effect of bisphosphonates depends on the correct use. Objective: the objective of this research was to conduct a review of the studies regarding the influence of mineral water on the absorption of bisphosphonates. Results and Discussion: calcium ions and bisphosphonates interact to form high molecular weight polynuclear and relatively insoluble complexes in the physiological pH range. The higher the calcium concentration of mineral water, the lower proportion of bisphosphonates is absorbed. The complexes may be more cytotoxic than their free forms. Filtration was found to remove 89% of calcium from the water on average. Conclusion: oral bisphosfonates must be taken with filtered water whenever possible. Mineral water containing high levels of calcium is not recommended when taking bisphosphonates.

Pharmacokinetic characteristics of fluticasone, salmeterol and tiotropium after concurrent inhalation

Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08–3.00 h, 0.03–0.10 h and 0.03–0.10 h, respectively) and were eliminated with mean half-lives of 9.29–10.44 h, 6.09–12.39 h and 0.25–47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250–750 µg and 50–150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.

Chromium oxide (51Cr2O3 ) used as biological marker was not absorbed by fish / Óxido de crômio (51Cr 2O3 ), usado como marcador biológico, não é absorvido por peixe

The aim of this study was to evaluate the rate absorption of radio-labeled chromium oxide (51Cr2O3), used as biological marker in nutrition studies with Nile tilapia Oreochromis niloticus. An experimental diet with approximately 58 µCi of specific activity of the element was encapsulated and fed daily to 35 adult Nile tilapia; a group of 35 fish was used as control feeding on a basal diet. At the beginning of the experiment five fish from each group were randomly selected and blood samples were drawn from control (BC) and experimental fish (BE). Fish were then euthanized by anesthetic overdoses and samples of the liver tissue (LT), renal tissue (RT), stomach without content (S), intestine without content (I), gills tissue (GT), muscle tissue (fillet; MT), visceral fat (VF), content of the digestive tract (CTDE) and water aquarium were collected from the experimental fish. The procedure was repeated daily for one week. Simple linear regressions were adjusted - days of collection vs. determination coefficients, and were established for statistical comparisons of the measured activity of 51Cr readings in sampled blood and tissues (logarithmic transformation) for samples of the control and experimental fish. No differences (P>0.05) were detected between samples from BC fish and BE, RT, VF, MT and LT of treated fish, but samples of GT, I, S, CTDE and WA from the tanks holding fish which received the experimental diet differed from control (P<0.05). The experimental results indicate that the trivalent chromium in the form of 51Cr2O3 was not significantly absorbed by the gastrointestinal tract, gills or another possible route of absorption under these experimental conditions and with Nile tilapia. Therefore, this marker was shown to be inert and can be safely used in nutrition studies.

O objetivo deste estudo foi avaliar a taxa de absorção de radiomarcador óxido de crômio (51Cr2O3), utilizado como marcador biológico em estudos de nutrição, com tilápia-do-nilo Oreochromis niloticus. Uma dieta experimental com cerca de 58µCi de atividade específica do elemento foi encapsulada, e 35 adultos de tilápia foram alimentados diariamente; um grupo de 35 peixes foi usado como controle e alimentado com uma dieta basal. No início do estudo, cinco peixes de cada grupo foram selecionados aleatoriamente, e amostras de sangue foram coletadas dos peixes controle (BC) e experimentais (BE). Os peixes foram sacrificados por overdose de anestésicos, e amostras do tecido do fígado (LT), rins (RT), estômago sem conteúdo (S), intestino sem conteúdo (I), brânquias (GT), tecido muscular (filé; MT), gordura visceral (VF), conteúdo do trato digestivo (CTDE) e água do aquário (WA) foram coletadas somente dos peixes experimentais. O processo foi repetido diariamente durante uma semana. As regressões lineares simples foram ajustadas - dias de coleta versus coeficientes de determinação - e foram estabelecidas para comparações estatísticas da leitura das atividades medidas de 51Cr (transformação logarítmica) nas amostras dos peixes controle e experimentais. Não foram detectadas diferenças (P>0,05) entre as amostras BC dos peixes controle e BE, RT, VF , MT e LT dos peixes experimentais, mas as amostras de GT, I, S, CTDE e WA dos peixes que receberam a dieta experimental apresentaram diferença significativa em relação aos que receberam a dieta controle (P<0,05). Os resultados experimentais indicam que o crômio trivalente na forma de 51Cr2O3 não foi significativamente absorvido pelo trato gastrointestinal, pelas brânquias ou por outra via possível de absorção nessas condições experimentais e com tilápia do Nilo. Portanto, esse marcador demonstrou ser suficientemente inerte, o que torna seguro seu uso em estudos de nutrição.

Effect of mouse antisera targeting the Phlebotomus papatasi midgut chitinase PpChit1 on sandfly physiology and fitness

In sandflies, the absence of the peritrophic matrix (PM) affects the rate of blood digestion. Also, the kinetics of PM secretion varies according to species. We previously characterised PpChit1, a midgut-specific chitinase secreted in Phlebotomus papatasi (PPIS) that is involved in the maturation of the PM and showed that antibodies against PpChit1 reduce the chitinolytic activity in the midgut of several sandfly species. Here, sandflies were fed on red blood cells reconstituted with naïve or anti-PpChit1 sera and assessed for fitness parameters that included blood digestion, oviposition onset, number of eggs laid, egg bouts, average number of eggs per bout and survival. In PPIS, anti-PpChit1 led to a one-day delay in the onset of egg laying, with flies surviving three days longer compared to the control group. Anti-PpChit1 also had a negative effect on overall ability of flies to lay eggs, as several gravid females from all three species were unable to lay any eggs despite having lived longer than control flies. Whereas the longer survival might be associated with improved haeme scavenging ability by the PM, the inability of females to lay eggs is possibly linked to changes in PM permeability affecting nutrient absorption.

Tempo de passagem de duas dietas no trato gastrointestinal do peixe-boi da Amazônia Trichechus inunguis (Natterer, 1883) em cativeiro / Transit time of two diets in the gastrointestinal tract of the Amazonian manatee Trichechus inunguis (Natterer, 1883) in captivity

The objective of this study was to determine the transit time of two diets in the digestive tract of the Amazonian manatee in captivity. We tested separately two different diets: one composed exclusively of grass of the genus Brachiaria (experimental diet - ED- A 1) and the other composed of grass Brachiaria added with small portions of extruded pellets for horses (experimental diet ED- A 2). Two healthy adult manatees were selected and isolated from the rest and underwent a period of food acclimation with the experimental diets for 15 days. After this period, the experimental diet was marked with a plastic colored tape of 10-cm length and given to the animals. The manatees were monitored at intervals of 1 hour and all fecal material was collected until recovery of the markers. The mean transit time of ED - A1 was 123h57min , about 5.16 days and ED - A 2 was 125h04min or 5.21 days. There was no statistical difference (P <0.05) between the transit time of the two diets provided. The transit time observed (approximately 5 days) has also been reported by other authors for this species and is considered a strategy to increase the absorption time of food nutrients. Despite the small sample size, the results suggest that the use of pellets in the diet of the Amazonian manatee did not affect the transit time of the grass. Therefore, it is reasonable to believe that the introduction of concentrated food (pellets) does not affect the efficiency of the animal to digest and absorb food properly.

Com o objetivo de testar o tempo de passagem do alimento no trato digestório de peixes-bois da Amazônia em cativeiro, foram testadas separadamente duas dietas distintas. Uma composta exclusivamente de capim do gênero Brachiaria (dieta experimental - DE 1) e outra de capim do gênero Brachiaria acrescentado de pequenas porções de ração extrusada para eqüinos (dieta experimental - DE 2). Foram selecionados do plantel do INPA dois animais adultos machos sadios, os quais foram isolados dos demais e submetidos a um período de aclimatação às dietas experimentais por 15 dias. Após este período, as dietas foram marcadas com uma fita plástica de 10 cm e fornecidas aos animais que foram monitorados em intervalos de uma hora. Todo material fecal foi coletado até a recuperação dos marcadores plásticos. A média do tempo de passagem da DE 1 foi de 123h57min, cerca de 5,15 dias e da DE 2 foi de 125h04min ou 5,21 dias. Não houve diferença estatística (P<0,05) entre as dietas fornecidas. O tempo de passagem observado (aproximadamente 5 dias) coincide com o relatado por outros autores para a espécie, sendo esse tempo considerado uma estratégia para aumentar o tempo de absorção nutricional dos alimentos. Apesar do número reduzido de amostras, os resultados sugerem que o uso da ração na alimentação não interfere no tempo de passagem do capim pelo trato digestório do peixe-boi. Com isso, sugere-se que a introdução de alimento concentrado (ração) não afeta a eficiência na digestão e absorção correta do alimento.