A Review On Co-Processed Excipients: Current And Future Trend Of Excipient Technology

There is no single-component excipient fulfills all the requisite performance to allow an active pharmaceutical ingredient to be formulated into a specific dosage form. Co-processed excipient has received much more attention in the formulation development of various dosage forms, specially for tablet preparation by direct compression method. The objective of this review is to discuss the emergence of co-processed excipients as a current and future trend of excipient technology in pharmaceutical manufacturing. Co-processing is a novel concept of combining two or more excipients that possess specific advantages that cannot be achieved using a physical admixture of the same combination of excipients. This review article discusses the advantages of co-processing, the need of co-processed excipient, general steps in developing co-processed excipient, limitation of co-processed excipient, technologies used in developing co-processing excipients, co-processed excipients in the literature, marketed products and future trends. With advantages offered by the upcoming newer combination of excipients and newer methods of co-processing, co-processed excipients are for sure going to gain attraction both from academia and pharmaceutical industry. Furthermore, it opens the opportunity for development and use of single multifunctional excipient rather than multiple excipients in the formulation.

Advances in Study on Role of Cathepsin S in Irritable Bowel Syndrome / 胃肠病学

Irritable bowel syndrome(IBS)is a common functional intestinal disease,and its etiology and pathogenesis are not completely clear. The pathogenesis of IBS involves disturbed gastrointestinal motility,gut hypersensitivity,intestinal inflammation,immune dysfunction and brain-gut axis abnormality. Cathepsin S(CTSS)is a proteolytic enzyme widely distributed in various cell lysosomes,and participates in a variety of pathophysiological processes. Recent studies have shown that CTSS may be involved in the pathogenesis of IBS. This article reviewed the advances in study on role of CTSS in IBS.

Difficult Problems and Strategy on Diagnosis and Treatment of Gastroesophageal Reflux Disease / 胃肠病学

Gastroesophageal reflux disease(GERD)is a chronic and recurrent disease with a wide variety of symptoms,often overlapping with functional gastrointestinal disorders,having different response to proton pump inhibitor (PPI)therapy,and facing various challenging for diagnosis and treatment. It is important for improving the diagnosis via knowing well the clinical manifestations of GERD and related diseases,rational using PPI test,upper gastrointestinal endoscopy and ambulatory esophageal pH/impedance monitoring,and understanding the relationship between the symptoms and reflux events. Different strategies of maintenance therapy should be chosen in accordance with patient's condition for decreasing recurrence. Aggressive acid suppressive therapy,inhibiting gastroesophageal reflux and modulating esophageal hypersensitivity are the main treatment methods for patients with poor response to PPI after ruling out the non-GERD causes.

Lateralidad, perfil cognitivo y rendimiento escolar en pacientes con mielomeningocele / Laterality, cognitive profile, and school performance in children with myelomeningocele

El mielomeningocele (MMC) es la forma más grave de los disrafismos de la columna vertebral. Afecta a 1/1200 recién nacidos vivos. Su etiología es multifactorial. El 80% cursa con hidrocefalia (HC) asociada a malformación de Arnold Chiari. El coeficiente intelectual (CI) oscila en un rango entre fronterizo y normal promedio. La tasa mundial de la población general de zurdos es del 10% pero se describe un aumento de su presentación en niños con MMC. Además se evidencian déficits visoespaciales, grafomotores, atencionales, memorísticos, dificultades en aritmética y en la comprensión de textos. Materiales y métodos: Este es un trabajo analítico, descriptivo, transversal. Se evaluaron 179 pacientes derivados del Consultorio Interdisciplinario de MMC; edad: entre 5 años, 0 meses y 15 años, 11 meses. No se emplearon controles sanos. Instrumentos administrados: Stanford Binet IV, Prolec ­ Prolec-Se, Wrat3, TMT A y B, d2, Stroop y pruebas de lateralidad de Zazzo. Objetivo: Describir la lateralidad, el perfil cognitivo y el rendimiento escolar en pacientes pediátricos con patología de mielomeningocele, analizando también las funciones ejecutivas, los procesos atencionales, memorísticos y la modalidad escolar en la cual se encuentran inmersos. Resultados: El 20% (35/179 pacientes) con edades que oscilan entre los 5 años, 0 meses y 15 años, 11 meses han presentado lateralidad zurda, y de ellos presentaban antecedentes familiares de zurdera 26%. Se observó lateralidad cruzada en 6% y eran ambidiestros 11%. El perfil cognitivo de la muestra completa (N: 179) fue homogéneo en todas las áreas (verbal, abstracto/visual y memoria de corto plazo), arrojando puntuaciones fronterizas. En pruebas atencionales el 100% obtuvo niveles descendidos. Todos reportaron dificultades en el rendimiento escolar. Sólo el 14% tuvo plan de integración y el 11% accedió a algún tipo de tratamiento. Conclusiones: Los niños con MMC evidencian déficits neuropsicológicos y alta tasa de zurdera, siendo probablemente los problemas de lateralidad una de las causas que ocasionarían el bajo rendimiento escolar y afectando el rendimiento académico (AU)

Myelomeningocele (MMC) is the most severe form of spinal dysraphism, affecting 1/1200 live newborns. Its etiology is multifactorial. Overall, 80% develops hydrocephalus (HC) associated with an Arnold Chiari malformation. The intelligence quotient (IQ) ranges from borderline to average. The worldwide incidence in the general population of left-handedness is 10%; however, an increase is found among children MMC. Additionally, visuospatial, graphomotor, attention, memory deficits as well as difficulties in arithmetic and text comprehension is found. Material and methods: A cross-sectional, analytical, descriptive study was conducted. Overall, 179 patients aged between 5 years 0 months and 15 years 11 months referred from the interdisciplinary MMC clinic were evaluated. No healthy control group was used. Instruments administrated: Stanford Binet IV, Prolec ­ Prolec-Se, Wrat3, TMT A and B, d2, Stroop and Zazzo's laterality test. Aim: To describe laterality, cognitive profile, and school performance in pediatric patients with MMC, analyzing executive functions, attention and memory, and the school system the children were attending. Results: 20% (35/179 patients) aged between 5 years, 0 months and 15 years, 11 months were left-handed, 26% of whom had a family history of left-handedness. Cross dominance was observed in 6% and ambidexterity in 11%. Overall, the cognitive profile of the sample (N: 179) was homogeneous in all areas (verbal, abstract/visual, and short-term memory), with borderline scores. In attention tasks, levels were low in 100%. All children had difficulties in school performance. Only 14% had an integration program and 11% received some type of treatment. Conclusions: Children with MMC show neuropsychological deficits and a high rate of left-handedness, the latter of which may be one of the causes of poor school performance and affecting academic achievements (AU)

Impacto de la diabetes tipo 1 en el desarrollo neurocognitivo de niños entre 5 y 18 años / Impact of type-1 diabetes on neurocognitive development in children between 5 and 18 years of age

Introducción: la diabetes tipo 1 es la segunda enfermedad crónica más frecuente de la infancia. Dentro de sus comorbilidades de la diabetes tipo 1, los efectos sobre el riñón, la retina, los nervios, los vasos sanguíneos y el sistema cardiovascular son ampliamente conocidos, sin embargo y a pesar de su importancia, en los niños, aún se conoce poco acerca del impacto de la diabetes tipo 1 sobre el sistema nervioso central en desarrollo. Objetivo: estudiar el desarrollo neurocognitivo alcanzado por nuestros pacientes con diabetes tipo 1 de comienzo temprano, analizando su relación con el control metabólico de la enfermedad y con factores socio-ambientales. Material y Métodos: se realizó un estudio descriptivo, observacional y transversal, con análisis retrospectivo. Fueron incluidos los niños atendidos en el Hospital de Pediatría Garrahan, con diabetes tipo 1, con comienzo de la enfermedad antes de los 7 años de vida. Se evaluó perfil neurocognitivo incluyendo capacidad cognitiva general, razonamiento verbal y perceptivo motor, velocidad de procesamiento y memoria operativa. Las variables metabólicas analizadas fueron mal control por hiperglucemia o por hipoglucemia y grado de descompensación al debut. Resultados: El coeficiente intelectual total se relacionó significativamente con educación secundaria materna. (R2 0.56 F= 5.21, p= 0.01). El índice de comprensión verbal se relacionó significativamente tanto con el escore de hiperglucemia como con educación secundaria materna. (R2 0.56 F= 5.16, p= 0.01). El índice de velocidad de procesamiento presentó relación significativa solo con el valor de bicarbonato al debut. (R2 0.39 F= 3.72, p= 0.03) y el índice de memoria operativa presentó relación significativa con vivienda propia y valor de bicarbonato al debut. (R2 0.50 F= 5.32, p= 0.009). Los pacientes con mayores eventos de hipoglucemias no presentaron diferencias significativas en ninguna variable neurocognitiva con respecto a los demás. Conclusión: hemos hallado alteraciones neurocognitivas leves asociadas principalmente a hiperglucemia, grado de descompensación al debut y a causas socioambientales. Resulta clara la necesidad de alcanzar objetivos de control glucémico con el fin de evitar o retrasar la posible aparición de complicaciones crónicas entre las cuales deben incluirse las que afectan al sistema nervioso central en desarrollo (AU)

Introduction: Type-1 diabetes is the second-most common chronic disease in childhood. Among the co-morbidities of type-1 diabetes, kidney, retina, nerve, blood-vessel, and cardiovascular involvement is widely known; however, in spite of its importance in children little is known about the impact of type-1 diabetes on the developing central nervous system. Aim: To study neurocognitive development in our patients with early-onset type-1 diabetes, with a focus on the association with metabolic control of the disease. Material and Methods: A descriptive, observational, and transsectional study was conducted using retrospective data analysis. Children with type-1 diabetes with a disease onset before 7 years of age seen at the pediatric Hospital Garrahan were included in the study. The neurocognitive profile was assessed, including general cognitive abilities, verbal and perceptive motor reasoning, processing speed, and working memory. Metabolic variables evaluated were poor hyperglycemia control or hypoglycemia and degree of decompensation at onset. Results: Total intellectual quotient was significantly related to maternal secondary education (R2 0.56 F= 5.21, p= 0.01). Verbal comprehension index score was significantly associated both with hyperglycemia score and maternal secondary education (R2 0.56 F= 5.16, p= 0.01). Processing speed index was significantly related only to bicarbonate levels at onset (R2 0.39 F= 3.72, p= 0.03) and working memory index was significantly related to family homeownership and bicarbonate levels at onset (R2 0.50 F= 5.32, p=0.009). Patients with a greater number of hypoglycemia events did not have significant differences in any of the neurocognitive variables compared to the other children. Conclusion: We found that mild neurocognitive impairment was mainly associated with hyperglycemia, degree of decompensation at onset, and environmental causes. There is a clear need to achieve the goal of glycemia control so as to avoid or delay possible chronic complications including those that affect the developing central nervous system (AU)

Funciones ejecutivas y calidad de vida de pacientes pediátricos trasplantados hepáticos / Executive functions and quality of life in pediatric patients who underwent liver transplantation

Objetivos: caracterización de las Funciones Ejecutivas (FE) y Calidad de Vida (CV) en niños de 8 a 12 años con trasplante hepático (TxHep). Metodología: Se evaluó al primer paciente de la agenda de seguimiento de TxHep (37 niños). Excluidos 7: 6 por discapacidad intelectual: 16,6%, 1 desertó. Instrumentos: escala Graffar, WISC III, NEPSY II, d2, Test de Trazados A y B, y Peds QL. FE: 30 TxHep y 30 controles. (Statistical Package for Social Sciences, versión 11.5). Resultados: 53,3% diagnóstico de Falla Hepática Fulminante (FHF), 70% TxHep con dificultades escolares. CI total: diferencia estadísticamente significativa: p < 0.023; T test de Student (TtS), entre FHF (82 ± 8.2) y el resto TxHep (75.43 ± 6.5). 60% TxHep en el nivel fronterizo. Diferencias estadísticamente significativas FE: Flexibilidad cognitiva; Fijación de Metas; y Procesamiento de la Información. Calidad de Vida: déficit leve en el dominio Escolar (score Z, -0.88 ± 0.87) y en el Psicosocial (score Z, -0.63 ± 1.06), en el reporte de niños TxHep. Conclusiones: una muestra mas amplia podría diferenciar las FE y CV entre FHF y otros diagnósticos. La intervención oportuna del diagnóstico y terapia neurocognitivos favorecen el neurodesarrollo acompañando la sobrevida (AU)

Purpose: To describe executive functions (EF) and quality of life (QOL) in children between 8 and 12 years of age who underwent liver transplantation (LTx). Methods: Patients from the list of LTx patients in follow-up were evaluated (37 children). Excluded 7: 6 because of intellectual disability: 16.6%, 1 dropped out. Tools: Graffar index, WISC III, NEPSY II, d2, Trail Making Tests A and B, and Peds QL. EF: 30 LTx and 30 controls. (Statistical Package for Social Sciences, versión 11.5). Results: 53.3% had a diagnosis of acute liver failure (ALF), 70% of LTx had difficulties in their school performance. Total IQ: a significant statistical difference was found: p < 0.023; Student's t test (StT), between patients with ALF (82 ± 8.2) and the remaining LTx patients (75.43 ± 6.5). Sixty percent had a borderline level. Statistically significant differences in EF: Cognitive flexibility; Goal setting; and Information Processing speed. QOL: A mild deficit in the School (Z-score, -0.88 ± 0.87) and Psychosocial Domain (Z score, -0.63 ± 1.06) in the LTx children's report. Conclusions: A larger study sample will be useful to differentiate EF and QOL in LTx children with ALF and those with other diagnoses. Early intervention after diagnosis and neurocognitive therapy is important to improve patients' quality of survival (AU)

Funciones atencionales de pacientes pediátricos receptores de trasplante alogénico de células progenitoras hematopoyeticas / the function of attention in pediatric allogenic hematopoietic stem cell transplant recipients

Se incluyeron 28 pacientes, el 75% de sexo masculino, con una mediana de edad de 13 años (r 8-17). Se utilizaron las siguientes pruebas: Enfocar-Ejecutar: Stroop y Trail Making A; Sostener la Atención: D2; Codificar la Información (Memoria de Trabajo): Tomal; Capacidad de cambiar la atención adaptativamente: Trail Making B y Wisconsin. Se administró también un test de inteligencia abreviado (KBit). Los pacientes fueron evaluados antes del ingreso a la unidad de trasplante y un año después si se encontraban en seguimiento ambulatorio y en remisión de la enfermedad que motivo el TCPH. También fue estudiado un grupo control de niños y adolescentes sanos, sin trastornos de aprendizaje, de dos escuelas. Se compararon los resultados de los pacientes antes del TCPH con el grupo control y los resultados pre y post TCPH de los 17 que pudieron ser evaluados al año. Se utilizó la prueba t de Student y se consideró significativa una p< 0,05. En la evaluación previa al TCPH los pacientes presentaban resultados significativamente inferiores a los controles para las siguientes prueba: Wisconsin, Trail Making A y B, Stroop, D2 y K-Bit, lo que implicaría compromiso de las siguientes funciones cognitivas: Atención sostenida, Enfocar - ejecutar y Funciones ejecutivas respectivamente, debido a que tomamos el modelo de Misky en donde el cambio adaptativo de la atención está implicando a las funciones ejecutivas. En la evaluación posterior al TCPH se observaron pocas diferencias respecto a la evaluación inicial, que involucraron el sostén de la atención, la capacidad de cambiar el foco de la misma y las funciones ejecutivas. Conclusión: los pacientes llegan al TCPH con un compromiso previo de sus funciones atencionales que podría estar relacionado con las limitaciones para la actividad escolar, producto de la enfermedad y tratamientos previos. Esta situación podría afectar su rendimiento académico posterior y ser un factor de riesgo de fracaso escolar.

Niños con altas capacidades / Highly gifted children

El presente trabajo intenta realizar una descripción del perfil cognitivo de los niños con altas capacidades y dificultades que pueden asociarse. La superdotación supone una inteligencia muy superior respecto a su grupo de edad medida a través de las pruebas de inteligencia. Estos sujetos poseen gran creatividad, imaginación, sensibilidad y curiosidad insaciable. El perfil cognitivo evidencia un elevado nivel lingüístico, pero generalmente con mayor descompensación de las habilidades de procesamiento gráfico. Un niño con altas capacidades no sólo cuestiona sus altos potenciales, sino también su existencia, ocasionándole lo que se denomina “Síndrome de Bajo Rendimiento (SBR)”. Cuando se encuentran en esta situación, ocultan sus capacidades para evitar ser rechazados o discriminados por sus compañeros. En esta etapa los sujetos sobresalientes, pueden confundirse con niños con trastornos de aprendizaje, trastornos por déficit de atención, Sme. de Asperger u otras patologías, presentando distintos perfiles y generándoles dificultades en las habilidades sociales, trastornos conductuales, etc., tanto en el ámbito escolar como extraescolar.

The relationship between BMI and striatal dopamine transporter with 99Tcm-TRODAT-1 brain SPECT / 中华核医学杂志

Objective To assess the relationship between the BMI and the brain DAT, and the influence of BMI on the brain SPECT imaging with 99Tcm-TRODAT-1. Methods MRI and 99Tcm-TRODAT-1SPECT imaging were performed in 31 healthy volunteers(16 males and 15 females), and then the three-dimensional reconstruction of SPECT images were completed. Based on the MRI images, right striatum (RST) and the left striatum (LST) were drawn as ROI on the 4 most clearly consecutive transverse slices.The cerebellum (CB) was taken as the background reference area and the corresponding uptake ratios of ST/CB, LST/CB and RST/CB were calculated. The Pearson correlation tests for radio-uptake ratios (ST/CB, LST/CB, RST/CB), BMI and age were performed, Then multiple linear regression analysis using ST/CB as dependent variable and BMI and age as independent variables was performed. SPSS 15.0 was used in data analysis. Results The ST imaging was symmetrical. The radioactivity was higher in the ST front area than that of the back area. The average uptake ratios of ST/CB, LST/CB, RST/CB were 1.71±0.16,1.70 ± 0. 16 and 1.72±0.17 respectively, in which the three ratios of the female were 1.74 ± 0. 18, 1.71±0. 19 and 1.76 ± 0. 19 respectively and those of the male were 1.68 t 0. 14, 1.68 ± 0. 13 and 1.69± 0.15respectively. ST/CB, LST/CB and RST/CB were negatively correlated with patients'BMI (r = -0. 53,-0.57,-0.47, all P＜0.05). The ST/CB was negatively correlated with patients' age(r=-0.39, P=0. 03). The multiple linear regression analysis showed that the BMI was significant independent variable (β=-0.53, t= -3.36, P=0. 002). Conclusions TheSTDAT,evel may decrease as patients' BMI and age increase. Females' DAT level is slightly higher than males'. For ST DAT imaging, age, gender and BMI should be all taken into consideration.

Association of Health-related Quality of Life with Health Examination and Lifestyles of Government Managers in China / 华中科技大学学报（医学）（英德文版）

In order to study the association of each item of a health examination and lifestyles with health-related quality of life (HRQoL), a cross-sectional survey by a self-administered questionnaire using the 12-Item Short Form Health Survey (SF-12, version 1) was conducted on 145 government managers that took health examinations in Tongji Hospital, Wuhan, China during 2005. The results showed that the determinations of organic functions including BMI, hemoglobin, blood platelet count,urine protein, urine WBC and lipid metabolism (LDL) were associated with HRQoL. The lifestyle items including age, sex, life satisfaction, drinking alcohol and kind of alcohol drunk, drinking tea,sleep quality and adhering to bedtime, working overtime, work stress were associated with HRQoL in the multiple regression models. Sex, age and life satisfaction were the lifestyle items most closely associated with HRQoL, while LDL, hemoglobin and urine protein were the health examination items most closely associated HRQoL. This study revealed that both lifestyle and health examination items were associated with HRQoL.