8 research outputs found
Growth study of hierarchical Ag<sub>3</sub>PO<sub>4</sub>/LaCO<sub>3</sub>OH heterostructures and their efficient photocatalytic activity for RhB degradation
No full textWe demonstrate a simple, cost effective co-precipitation method to synthesize APO/LCO heterostructures and investigate the effect of a mixed solvent system (H2O:THF) on the growth of microstructures.</p
Does 3-day course of oral amoxycillin benefit children of non-severe pneumonia with wheeze: a multicentric randomised controlled trial.
No full textWHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2-59 months of age, who received either oral amoxycillin (31-54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.ClinicalTrials.gov NCT00407394
Avaliação de complexos de sílica mesoporosa (SBA-15) com fármacos (Naproxeno e Estavudina)
Get PDFDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Farmácia.Materiais mesoporosos têm recebido muita atenção devido as suas características atrativas como estrutura de mesoporos estáveis, grande área superficial (acima de 1500 m2/g), grande volume de poro, tamanho de poro regulável (2-10 mn) e superfície com caráter hidrofílico. Recentemente uma nova aplicação para a sílica mesoporosa como liberação de fármacos tem sido explorada devido a sua natureza não-tóxica e boa biocompatibilidade. SBA-15 é uma sílica mesoporosa ordenada com características adequadas e boa estabilidade térmica. Por esta razão, a SBA-15 é um potencial candidato a um sistema de liberação de fármacos. O naproxeno é um derivado do ácido propiônico e o naproxeno sódico é seu sal. É um fármaco antiinflamatório não-esteroidal (AINEs) que inibe a síntese de prostaglandinas. O naproxeno é um fármaco lipossolúvel, praticamente insolúvel em água a pH baixos e facilmente solúvel em pH mais elevados, é solúvel em etanol e metanol. Seu coeficiente de partição octanol/água a pH 7.4 é de cerca de 2.A estavudina é um antiretroviral representante da classe de inibidores de transcriptase reversa e é comumente utilizada na terapia contra o HIV. A estavudina, também chamada de d4T, é um fármaco hidrofílico, solúvel em água e parcialmente solúvel em etanol. Outra importante característica é seu coeficiente de partição (Log P(octanol/água)): -0.72 (ou 0.14). Este valor lhe confere a característica hidrofílica o que explica sua solubilidade em água. O objetivo do trabalho foi avaliar a complexação de SBA-15 com dois fármacos modelos (naproxeno e estavudina). Algumas técnicas foram usadas: TG, DSC, FTIR, MEV e CLAE. A partir dos resultados obtidos foi possível observar a complexação do naproxeno com a SBA-15, o que não ocorreu com a estavudina. Isso se deve ao fato de o naproxeno possuir característica de solubilidade semelhante a sílica mesoporosa SBA-15, facilitando a complexação. O controle do pH influenciou na ligação do naproxeno com os grupos funcionais da sílica. O percentual de fármaco presente na sílica foi quantificado por CLAE e resultou em cerca de 32 %
Evaluation of the Liquisolid Compacts Using Response Surface Methodology
Get PDFLiquisolid Compacts technique has potential to develop sustained release formulations. It involves conversion of liquid drug (either solution or suspension) in non-volatile solvent into free-flowing, non adherent, dry looking and readily compressible powder. In the present work, an attempt was made to develop such formulation of Diltiazem HCl and evaluation using Response surface methodology. Liquisolid compacts were prepared by dissolving Diltiazem HCl in Polyethylene Glycol 400. Then a binary mixture of carrier-coating material, Avicel and Aerosil, was added to liquid medication under continuous mixing in mortar. The HPMC K4M was used as adjuvant for sustaining the drug release. The pre-compression studies for all the formulations were also carried out. The Liquisolid compacts were evaluated in-vitro dissolution studies. The experimental data was evaluated using Design Expert Software. The % Drug Concentration, ratio of Carrier to Coating material and amount of HPMC K4M are taken as three factors. Response Surface methodology was used to study the influence of the each factor on the response. The present investigation showed that Polyethylene Glycol 400 has important role in release retardation of drug in Liquisolid compacts. The reduction in Tg can be reason for same. The Response surface methodology showed that all the factors were significantly affect the release at 16 hrs.
Evaluation of the Liquisolid Compacts Using Response Surface Methodology
Get PDFLiquisolid Compacts technique has potential to develop sustained release formulations. It involves conversion of liquid drug (either solution or suspension) in non-volatile solvent into free-flowing, non adherent, dry looking and readily compressible powder. In the present work, an attempt was made to develop such formulation of Diltiazem HCl and evaluation using Response surface methodology. Liquisolid compacts were prepared by dissolving Diltiazem HCl in Polyethylene Glycol 400. Then a binary mixture of carrier-coating material, Avicel and Aerosil, was added to liquid medication under continuous mixing in mortar. The HPMC K4M was used as adjuvant for sustaining the drug release. The pre-compression studies for all the formulations were also carried out. The Liquisolid compacts were evaluated in-vitro dissolution studies. The experimental data was evaluated using Design Expert Software. The % Drug Concentration, ratio of Carrier to Coating material and amount of HPMC K4M are taken as three factors. Response Surface methodology was used to study the influence of the each factor on the response. The present investigation showed that Polyethylene Glycol 400 has important role in release retardation of drug in Liquisolid compacts. The reduction in Tg can be reason for same. The Response surface methodology showed that all the factors were significantly affect the release at 16 hrs.
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries.
No full textStudy of the inhibitory potential of xanthones from Garcinia mangostana (Clusiaceae) on three digestive enzymes related to obesity and type 2 diabetes in search of molecules with multitarget action
No full textilustraciones, fotografías, gráficas, tablasGarcinia mangostana (Clusiaceae), conocida popularmente como mangostino, es una especie de importancia económica a nivel mundial que se caracteriza por contener una amplia diversidad de xantonas, las cuales tienen la capacidad de inhibir enzimas digestivas como α-amilasa (AA), α-glucosidasa (AG) y lipasa pancreática (LP). Estas enzimas juegan un papel importante en el metabolismo de carbohidratos y lípidos, por lo que suelen ser atractivas dianas terapéuticas para el tratamiento de la diabetes tipo 2 y la obesidad. Existe una estrecha correlación entre estas dos enfermedades, por lo que en las últimas décadas muchas investigaciones se han enfocado en la búsqueda de moléculas con acción polifuncional para tratar de manera simultánea estas dos patologías. En este sentido, G. mangostana es un objeto interesante de estudios debido a que varios de sus componentes químicos causan inhibiciones en diferentes enzimas digestivas. La presente investigación contribuye a la búsqueda de moléculas con potencial inhibitorio multidiana frente a lipasa pancreática, α-amilasa y α-glucosidasa, a partir de un estudio de las xantonas provenientes de G. mangostana. La metodología incluyó el estudio fitoquímico biodirigido sobre el pericarpio de los frutos de G. mangostana, para aislar e identificar una serie de xantonas con potencial inhibidor sobre las enzimas diana de interés. Adicionalmente, se realizó la síntesis de algunos derivados a partir del constituyente mayoritario. Posteriormente, se determinó la concentración inhibitoria, el tipo de inhibición y el modo de unión que ejercen las xantonas sobre las enzimas digestivas. Finalmente, se realizó un estudio de optimización farmacodinámica con cada blanco enzimático tomando como base la molécula α-mangostina, para predecir posibles moléculas con acción multidiana y mayor afinidad frente a LP, AG y AA. Se realizó la síntesis de algunas de las moléculas optimizadas y se determinó el efecto que ejercen sobre las enzimas digestivas. El estudio químico biodirigido permitió determinar que en la fracción de DCM se concentra la actividad inhibitoria sobre las tres enzimas digestivas (LP, AG y AA). A partir de la fracción de DCM se logró el aislamiento e identificación de cinco xantonas preniladas, entre las que se encuentran 9-hidroxicalabaxantona (Gm-1), 8-desoxigartanina (Gm-2), gartanina (Gm-3), α-mangostina (Gm-4) y γ-mangostina (Gm-5). Adicionalmente, a partir del constituyente mayoritario Gm-4 se sintetizaron los derivados Gm-6 a Gm-11, destacándose la propuesta de una nueva metodología libre de disolvente y por irradiación con microondas para la obtención de compuestos aromáticos con ciclo tetrahidropirano, a partir de precursores aromáticos hidroxilados con una cadena prenilada vecinal. Entre los compuestos aislados y sintetizados se destacan Gm-4 (CI50 AA = 317,6 ± 4,3 μM, CI50 AG = 31,6 ± 2,6 µM y CI50 LP = 50,6 ± 6,7 μM) y Gm-6 (CI50 AA = 164,4 ± 28,6 μM, CI50 AG = 33,3 ± 4,1 µM y CI50 LP = 69,2 ± 6,9 μM) por su mayor acción multidiana sobre las tres enzimas. De manera general, con los estudios de cinética enzimática y de acoplamiento molecular, se encontró que las xantonas bioactivas ejercen su acción sobre AA en su mayoría mediante una inhibición de tipo competitivo, mientras que sobre AG predomina la inhibición de tipo mixto, y frente a LP la mayoría de los inhibidores son de tipo no competitivo. Por último, el estudio optimización farmacodinámica sobre Gm-4 permitió proponer 10 moléculas optimizadas, de las cuales se sintetizaron tres sin reportes previos en la literatura y que fueron denominadas como Gm-12, Gm-13 y Gm-14. Estas moléculas presentaron acción inhibitoria frente a LP, AG y AA, destacándose Gm-14 por su acción inhibitoria polifuncional, y por ser el único compuesto con el que se logró optimizar de manera simultánea la actividad inhibitoria frente a AG y AA. Adicionalmente, se estableció que los compuestos optimizados son de tipo competitivo para AA, de tipo no competitivo para AG, y no competitivo y acompetitivo para la enzima LP. (Texto tomado de la fuente)Garcinia mangostana (Clusiaceae), popularly known as mangosteen, is a species of economic importance worldwide that is characterized by containing a wide variety of xanthones, which can inhibit digestive enzymes such as α-amylase (AA), α- glucosidase (AG) and pancreatic lipase (LP). These enzymes play an important role in carbohydrate and lipid metabolism and are therefore often attractive therapeutic targets for the treatment of type 2 diabetes and obesity. There is a close correlation between these two diseases, reason why in the last decades many investigations have focused on the search for molecules with multitarget action to treat these two diseases simultaneously. In this sense, G. mangostana is an interesting object of study because several of its chemical components cause inhibitions in different digestive enzymes. The present investigation contributes to the search of molecules with multitarget inhibitory potential against pancreatic lipase, α-amylase and α-glucosidase, based on a study of xanthones from G. mangostana. The methodology included the bioguiated phytochemical study on the pericarp of G. mangostana fruits, to isolate and identify a series of xanthones with inhibitory potential on the target enzymes of interest. Additionally, some derivatives were synthesized from the majority constituent. Subsequently, the inhibitory concentration, the type of inhibition and the binding mode exerted by xanthones on digestive enzymes were determined. Finally, a pharmacodynamic optimization study was carried out with each target enzyme based on the α-mangostin molecule, to predict possible molecules with multitarget action and higher affinity against LP, AG and AA. The synthesis of some of the optimized molecules was carried out and the effect they exert on digestive enzymes was determined. The bioguiated chemical study made it possible to determine that the inhibitory activity on the three digestive enzymes (LP, AG and AA) is concentrated in the DCM fraction. From the DCM fraction, the isolation and identification of five prenylated xanthones was achieved, among which are 9-hydroxylabaxanthone (Gm-1), 8-deoxygartanine (Gm-2), gartanine (Gm-3), α- mangostin (Gm-4) and γ-mangostin (Gm-5). Additionally, from the majority constituent Gm-4, the derivatives Gm-6 to Gm-11 were synthesized, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle, from hydroxylated aromatic precursors with a neighboring prenylated chain. Among the isolated and synthesized compounds, Gm-4 (IC50 AA = 317.6 ± 4.3 μM, IC50 AG = 31.6 ± 2.6 µM and IC50 LP = 50.6 ± 6.7 μM) and Gm-6 (IC50 AA = 164.4 ± 28.6 µM, IC50 AG = 33.3 ± 4.1 µM and IC50 LP = 69.2 ± 6.9 µM) due to its greater multitarget action on the three enzymes. In general, with the enzymatic kinetics and molecular coupling studies, it was found that bioactive xanthones exert their action on AA mostly through competitive inhibition, while on AG mixed-type inhibition predominates, and against LP most of inhibitors are non-competitive. Finally, the pharmacodynamic optimization study on Gm-4 allowed proposing 10 optimized molecules, of which three were synthesized without previous reports in the literature and which were called Gm-12, Gm-13 and Gm-14. These molecules showed inhibitory action against LP, AG and AA, with Gm-14 standing out for its polyfunctional inhibitory action, and for being the only compound with which it was possible to simultaneously optimize the inhibitory activity against AG and AA. Additionally, it was established that the optimized compounds are competitive inhibitors against AA, non-competitive for AG and non-competitive and uncompetitive for the LP enzyme. (Text taken from source)Apoyo financiero del Ministerio de Ciencia, Tecnología e Innovación (MinCiencias) a través del contrato 003-2017 con código 110174559038, financiado a través de la convocatoria nacional de proyectos para el fortalecimiento de la investigación, creación e innovación de la universidad nacional de Colombia 2016-2018. Apoyo al Joven Talento Juan Camilo Cardozo-Muñoz a través del contrato 907-2019 de la convocatoria 850-2019 para el fortalecimiento de proyectos de investigación de CTeI en ciencias médicas y de la salud con talento joven e impacto regional.MaestríaMagíster en Ciencias - QuímicaBioprospección en agentes fitosanitarios y terapéutico
