Assessment of Natural Sunlight Protection Provided by 10 High-SPF Broad-Spectrum Sunscreens and Sun-Protective Fabrics.

In 1978, the FDA Advisory Panel proposed both indoor and natural sunlight SPF testing methods but reverted to indoor testing only in 1993. Today's sunscreen sun protection and broad-spectrum claims are based on mandated clinical tests using solar simulators and in vitro spectrophotometers. This research evaluated the protection of 10 high-SPF (30-110), broad-spectrum sunscreen products, as well as 6 sun-protective fabrics against natural sunlight in Arequipa, Peru. Each of the 17 subjects was exposed to natural sunlight for 1 h and 59 min under clear skies, with temperatures and humidity similar to those in an indoor clinical laboratory. Test sites were photographed 16-24 h later. Four dermatologists evaluated the photographs for erythema and persistent pigment darkening (PPD). Perceptible sun-induced skin injury (sunburn and/or pigmentation) was detected at 97% of the sunscreen-protected scores. The most sun-sensitive subjects obtained the least erythema protection. The higher the SPF was, the higher the erythema protection, but the intensity of PPD was also higher. The 2 sunscreens using only FDA-approved sunscreen filters rated 30 SPF and 45+ SPF performed poorly: Eighty-one percent of the 136 scores were graded 1 minimal erythema dose or higher erythema, achieving, at a maximum, SPF of 5-7 in natural sunlight. Sun-protective fabrics tested provided excellent sun protection. The erythema and PPD observed through the sunscreens in less than 2 h are incongruous with the broad-spectrum, high-SPF sunscreen claims. Reapplying these sunscreens and staying in the sun longer, as stated on the product labels, would have subjected the subjects to even more UV exposure. High-SPF, broad-spectrum sunscreen claims based on indoor solar simulator testing do not agree with the natural sunlight protection test results.

Ensemble learning application to discover new trypanothione synthetase inhibitors.

Trypanosomatid-caused diseases are among the neglected infectious diseases with the highest disease burden, affecting about 27 million people worldwide and, in particular, socio-economically vulnerable populations. Trypanothione synthetase (TryS) is considered one of the most attractive drug targets within the thiol-polyamine metabolism of typanosomatids, being unique, essential and druggable. Here, we have compiled a dataset of 401 T. brucei TryS inhibitors that includes compounds with inhibitory data reported in the literature, but also in-house acquired data. QSAR classifiers were derived and validated from such dataset, using publicly available and open-source software, thus assuring the portability of the obtained models. The performance and robustness of the resulting models were substantially improved through ensemble learning. The performance of the individual models and the model ensembles was further assessed through retrospective virtual screening campaigns. At last, as an application example, the chosen model-ensemble has been applied in a prospective virtual screening campaign on DrugBank 5.1.6 compound library. All the in-house scripts used in this study are available on request, whereas the dataset has been included as supplementary material.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review.

Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction.

Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS).

The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P(oct) value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).

Development and evaluation of a floating multiparticulate gastroretentive system for modified release of AZT.

The aim of this study was to develop and evaluate a floating multiparticulate gastroretentive system for the modified release of zidovudine (AZT). AZT was used as a model drug water-soluble at therapeutic doses. The floating gastroretentive system was obtained by co-precipitation, after solvent diffusion and evaporation. The proposed system was evaluated in vitro for particle morphology, lag time and floating time, loading rate, release profile, and the release kinetic of AZT release. AZT's physico-chemical characteristics were evaluated by differential scanning calorimetry (DSC), X-ray diffraction (XDR) and infrared spectroscopy (IR). The particles obtained were sphere-shaped, hollow, and had porous walls. The floating was immediate, and floating time was higher than 12 h. The loading rate was 34.0 ± 9.0%. The system obtained had an extended release. DSC and XDR results showed a modification in AZT's solid state. IR spectroscopy revealed that the chemical structure of the AZT was unchanged. The hollow microballoons presented gastroretentive, floating, and extended-release properties.

Evaluation of blockbuster drugs under the rule-of-five.

The current drug research techniques, combinatorial synthesis and high throughput screening, enabled the obtaining and pre-evaluation of thousands of compounds in short time. In order to chose the best hits to become leads, observation of drug-likeness tries to optimize this selection. Probably, the most widely used filter is Lipinski's Rule-of-five, which proposes that molecules with poor permeation and oral absorption have molecular weight > 500, Clog P > 5, hydrogen-bond donor > 5 and hydrogen-bond acceptor > 10. In order to evaluate the Rule-of-five, the top pharmaceutical products in 2007 were analyzed. Among 60 drugs, 7 (atorvastatin, montelukast, docetaxel, telmisartan, tacrolimus, leuprolide and olmesartan) did not fit the rule, and 5 failed only one of the threshold values. It was possible to conclude that the rule is very useful to select better compounds in chemolibraries, but it must be used carefully and with criteria, to avoid a possible exclusion of promising compounds.

[Intersectorial policy concerning medicinal plants of the State of Rio Grande do Sul: as viewed by faculty members]. / Politica intersetorial de plantas medicinais do Estado do Rio Grande Do Sul: visão docente.

This survey aimed detecting the knowledge of university faculty members of the southern region of the state of Rio Grande do Sul, Brazil, in the Intersectorial Policy of Medicinal Plants of the State of Rio Grande do Sul. This quantitative survey used a sample size of 185 professors (61.7%). It was found that 91.50% of the interviewed professors did not know this policy. This suggests that, despite the existence of a policy on medicinal plants in the state of Rio Grande do Sul, is not well disseminated in the academia, which hinders its knowledge among faculty members.

Quality control validation for exogenous natural surfactant labeled with 99mTc.

OBJECTIVE: Exogenous natural surfactant (ENS) labeled with 99mTc shows an elevated lung specificity allowing the acquisition of high-quality images for ventilation scintigraphy. METHODS: The methods for 99mTc-ENS quality control (physical properties, pH determination, radiochemical studies, and biologic studies) were evaluated and validated. RESULTS: The physical properties of the nonradioactive precursor and of the radiopharmaceutical were analyzed as general descriptors of the product. The pH of the radiopharmaceutical was determined by using pH test papers, a method described and validated in the United States Pharmacopeia. Chromatographic studies performed using the acetone/Whatman-1 paper system were validated as a method to evaluate the radiochemical purity of the 99mTc-ENS. Biodistribution studies on rats after intratracheal administration were validated as a method to estimate the radiopharmaceutical biodistribution in humans. CONCLUSION: The proposed method for 99mTc-ENS quality control studies and stability studies was evaluated and validated following international standards.

Guía de práctica clínica basada en la evidencia para el manejo de la paciente embarazada que requiera tratamiento endodóntico / Evidence-based clinical practice guide for the management of the pregnant patients requiring endodontic treatment

Antecedentes: el tratamiento odontológico de los pacientes sistémicamente comprometidos tiene cada vez más importancia en el campo de la salud bucal. El sistema general de seguridad social actual en Colombia crea la necesidad de establecer protocolos para el diagnóstico y tratamiento de las diferentes patologías, con evidencia científica para el mejoramiento en la calidad de la atención de los usuarios. La mayoría de los protocolos que existen actualmente para el manejo del paciente con compromiso sistémico y diangóstico de patología bucal, se presentan como revisiones teóricas con poca aplicabilidad clínica o con una inapropiada sustentación científica; de igual forma, se encuentra diversidad de procedimientos terapéuticos para abordar una mismma patología, generando serias dificultades para unificar criterios de planes de tratamiento en este grupo de pacientes. Objetivo: diseñar guías de práctica clínica bassadas en la evidencia para el manejo del paciente sistémicamente comprometido que requiera tratamiento. En este artículo se presenta una revisión que concierne a la condición sistémica del embarazo. Métodos: revisión sistemática de la literatura y desarrollo de guías de práctica clínica con metodología de medicina basada en la evidencia. Resultados: desarrollo de la guía de práctica clínica basada en la evidencia para el manejo de la paciente embarazada que requiera tratamiento endodóntico. Conclusiones: la realización de esta guía ofrece una ilustración práctica de los puntos críticos de la toma de decisiones para el tratamiento endodóntico de la paciente embarazada (uso de anestésicos, analgésicos, antibióticos y toma de radiografías) y garantiza que éstas sean tan realizables y éticas como sea posible

Evolución histórica de los medicamentos no incluidos en la lista oficial (claves) de la CCSS / Historical evolution of medicines not including in the official list (key) of the CCSS

En el contexto de la Seguridad Social de Costa Rica se cuenta con la Lista Oficial de Medicamentos (LOM), que traduce la selección de los fármacos necesarios para atender las necesidades sanitarias de la población asegurada. Como un mecanismo para dar resolución a necesidades excepcionales de medicamentos, se dispone de la opción para gestionar claves de autorización para medicamentos no LOM a cargo institucional. El objetivo de esta presentación es exponer una breve reseña de la evolución histórica de las claves, con base en la información contenida en los archivos disponibles y las base de datos. La alternativa del sistema de claves para medicamentos no LOM se ha documentado desde 1985, cuando se otorgaron 387 claves. La confirmación de un constante crecimiento de las claves confirma la vigencia de esta alternativa a lo largo de los años, hasta llegar a 3848 claves durante el año 2001, aunque la gran mayoría de los producos autorizados a la fecha ya están incluidos en a LOM. Durante el primer semestre de 2002, los medicamentos más solicitados fueron Angiotensina II, Capecitabina, los inhibidores de Aroatasa (letrozol y otros) y la Amifostina. Se concluye que la opción de brindar medicamenots no LOM a cargo institucional a una minoría de pacientes tributarios, que por su condición clínica diferencial o por la excepcionalidad de su diagnóstico no está cubierto, constituye un recurso real en procura de asegurar una intervención farmacológica eficaz y segura a los pacientes. Palabras clave: Medicamentos, fármacos, Lista Oficial de Medicamentos.

Qué antibióticos prescribimos los dentistas? / Which antibiotics do dentists prescribe?

Las infecciones odontogénicas son comunes en la práctica del cirujano dentista, el tratamiento consiste en el establecimiento de un drenaje y en la eliminación de la fuente de infección que en ocasiones puede ser acompañado por la prescripción de antibióticos. Para conocer qué antibióticos prescriben los cirujanos dentistas, se circuló un cuestionario entre 303 dentistas de tres ciudades de la república mexicana. El antibiótico más prescripto fue la ampicilina (23 por ciento), seguido de la eritromicina (11 por ciento) y la penicilina V con un 10 por ciento. La duración del tratamiento también fue variable, siendo el esquema de 7 días (50.87 por ciento) el más frecuente, seguido de menos de 7 días (35.19 por ciento) y de más de 7 días, 13,93 por ciento. Actualmente sabemos que las infecciones odontogénicas son polimicrobianas, con un 65 por ciento de microorganismos anaerobios y que la ampicilina tiene poca actividad contra anaerobios. Los resultaods de la encuesta sugieren, de manera indirecta, que en la mayor parte de los dentistas entrevistados no existe el conocimiento adecuado del tipo de microorganismo invlucrado en las infecciones odontogénicas y de la sensibilidad y resistencia bacteriana a los antibióticos necesarios para poder prescribir antimicrobianos

Manejo racional de medicamentos en hospitales: un componente del mejoramiento contínuo de la calidad / Drugs rational management in hospitals: a component of quality continuos improvement

El presente manual presenta 8 módulos de monitoreo-capacitación-planificación, dirigidos a los establecimientos de salud del Ministerio de Salud, que traducen el esfuerzo de sistematización de la propuesta metodológica e instrumental para mejorar la gestión de medicamentos. Contiene: Introducción, Abreviaturas, Como usar la Guía; así como los siguientes Módulos: 1. El Comité Farmacológico, 2. Selección de Medicamentos, 3. Evaluación de la Gestión de Medicamentos en el Hospital, 4. Prácticas de Prescripción, 5. Farmacia Hospitalaria, 6. Gestión del Comité Farmacológico, 7. Participación del Paciente en su Tratamiento, 8. Información de Medicamentos, asegurando su buen uso. Guía de Navegación del Web Site

Estudios de toxicología preclínica para nuevos farmacos / Preclinical toxicology studies for new drugs

El objetivo de los estudios toxicológicos preclínicos de los nuevos fármacos es la caracterización del impacto fisiológico consecuente a su administración del impacto fisiológico consecuente a su administración. Para este fin se requiere hacer estudios en animales de laboratorio u otros modelos experimentales que demuestren la toxicidad o innocuidad del fármaco en experimentación. En el presente trabajo se describen los principios, metodología y lineamientos recomendados a nivel internacional para los estudios agudos, subcrónicos, crónicos, genotóxicos, así como los de toxicología de la reproducción. Este tipo de estudios se están efectuando actualmente con el nuevo anticonvulsionante DL-4-hidroxi, 4-hidroxi, 4-etil, 4-fenil butiramida (HEPB)

[Intestinal absorption of glucose in anesthetized rats. I. Standardization of a method for screening of oral hypoglycemic agents]. / Absorção intestinal de glucose em ratos anestesiados. I. Padronização de método para "screening" de drogas hipoglicemiantes orais (DHO).

This paper presents a method for the screening of natural hypoglycaemic drugs that interfere with the intestinal absorption of glucose. Luminal perfusion of the small intestine (whole length) was carried out on 24 h fasted adult Wistar rats, anaesthetized with sodium pentobarbital. Two rubber Nelaton cannulae were introduced into the organ, the first at the proximal end of the duodenum, just after the pylorus and a second larger one near the ileo-cecal valve. After a preliminary washing with warm physiological saline to remove any alimentary residues and secretions, warm saline containing glucose (plain or with added putative absorption inhibitors), was then introduced into the gut. Ten minutes later the contents was expelled with air and the preparation fully washed with plain warm saline. All perfusates were separately collected up to volume in graduated flasks kept in chipped ice. The glucose concentration was measured in triplicate samples by the specific glucose-oxidase method. The intestinal absorption of the sugar was calculated by difference from the glucose concentration found in the initial solution and in the final perfusate. The method is reliable and highly reproducible.