Tacrolimus impairs airway mucociliary clearance of rats.

OBJECTIVES: Tacrolimus (TAC) is the most widely used immunosuppressive agent after lung transplantation. Considering that the ciliary beat frequency (CBF) mainly depends on the cytoplasmic calcium concentration and that TAC can affect this due to its binding with the intracellular immunophilin FKBP12, we hypothesized that TAC could also impair the airway mucociliary clearance of rats. METHODS: Sixty rats were divided into two groups (n = 30 each): Control = water; TAC = tacrolimus. After 7, 15 or 30 days of treatment, ten animals from each group were euthanized and the following parameters were studied: mucus transportability, CBF, mucociliary transport velocity (MCTV), and neutral and acid mucus production. RESULTS: There was a significant decrease in CBF (Control vs TAC: 7 days, p = 0.008; 15 days, p = 0.007; 30 days, p = 0.001) and MCTV (Control vs TAC: 7 days, p = 0.004; 15 days, p < 0.001; 30 days, p < 0.001) in all immunosuppressed animals. TAC therapy also caused an increase in acid mucus production at all treatment times (Control vs TAC: 7 days, p = 0.001; 15 days, p = 0.043; 30 days, p = 0.001). CONCLUSIONS: TAC impairs airway mucociliary clearance of rats.

Methylnaltrexone in the Management of Opioid-Associated Urinary Retention in Children.

OBJECTIVE: To evaluate the association between methylnaltrexone and urine output (UOP) in critically ill children with opioid-associated urinary retention. METHODS: This retrospective study included patients admitted to the pediatric intensive care unit between December 1, 2019, and November 30, 2020, who received methylnaltrexone for opioid-associated oliguria (spontaneous UOP below 1 mL/kg/hr and at least 1 dose of an opioid within the preceding 6 hours). RESULTS: Twenty-five patients (median age = 5.5 years, IQR 1.7-16.4; median weight = 19 kg, IQR 9-45) were included. Mean methylnaltrexone dose was 0.15 ± 0.006 mg/kg. A statistically significant increase in UOP from baseline to 6 hours following methylnaltrexone was observed (p = 0.001), but not all patients responded. Fourteen patients (56%) had no UOP following methylnaltrexone administration, while 11 (44%) demonstrated a robust increase (median = 0 mL/kg/hr at baseline [IQR 0-0] to 1.96 mL/kg/hr [IQR 1.08-2.22; p = 0.001]) within 6 hours following methylnaltrexone administration. Younger patients responded better than older patients (responder age = 2.5 years [IQR 0.8-7]) versus 11.4 years [IQR 1.75-17.5] for non-responders) (p = 0.04). Both intravenous (IV) and subcutaneous (SQ) routes were associated with an increase in UOP (IV, p = 0.04; SQ, p = 0.02). The effect persisted for up to 24 hours after administration. Sixty-four percent of patients required urinary catheter placement. Pain scores (averaged 6 hours before and after methylnaltrexone) remained unchanged (p = 0.44). CONCLUSIONS: Methylnaltrexone may increase spontaneous UOP in some children with opioid-associated urinary retention, but urinary catheterization rates remain high.

Machine learning prediction of side effects for drugs in clinical trials.

Early and accurate detection of side effects is critical for the clinical success of drugs under development. Here, we aim to predict unknown side effects for drugs with a small number of side effects identified in randomized controlled clinical trials. Our machine learning framework, the geometric self-expressive model (GSEM), learns globally optimal self-representations for drugs and side effects from pharmacological graph networks. We show the usefulness of the GSEM on 505 therapeutically diverse drugs and 904 side effects from multiple human physiological systems. Here, we also show a data integration strategy that could be adopted to improve the ability of side effect prediction models to identify unknown side effects that might only appear after the drug enters the market.

Knowledge of the consequences and use of drugs for CostaRica niversity students / Conhecimento das consequências e do uso de drogas em estudantes universitários costarriquenses / Conocimiento de las consecuencias y uso de drogas en estudiantes universitarios costarricenses

ABSTRACT Objective: to determine the relationship between knowledge of consequences and drug use in undergraduate students of a university in San José, Costa Rica. Method: the cross-sectional study examines the demographic profile of the sample and the relationship between knowledge of consequences, drug use and academic performance. The study focuses on three types of drugs: alcohol, marijuana and cocaine. Three variables will be analyzed: demographic data, knowledge of consequences and use of drugs. Results: the relationship between knowledge of consequences and use of drugs was made using of the T-test. The sample had 272 students, 28.2% (n=77) of them were men and 71.4% were women (n=195). They were selected from the areas of social sciences (n=137, 50.2%), and from the area of health sciences (n=136; 49.8%). Alcohol was the most used drug (n=217, 79.8%), followed by marijuana (n=72, 26.6%) and finally cocaine (n=3, 1.1%) in the last 12 months. Conclusion: the results shown indicate that there is no significant relationship between such variables. The findings are important at the level of drug policies to support the development of new preventive strategies for drug use.

RESUMO Objetivo: determinar a relação entre o conhecimento das consequências e o uso de drogas em estudantes de graduação de uma universidade em San José, Costa Rica. Método: este estudo, de corte transversal, examina o perfil demográfico da amostra e a relação entre o conhecimento das consequências, o uso de drogas e o desempenho acadêmico. A pesquisa centra-se em três tipos de drogas: álcool, maconha e cocaína. Três variáveis foram analisadas: os dados demográficos, o conhecimento das consequências e o uso de drogas. Resultados: a relação entre o conhecimento das consequências e o uso de drogas foi realizada através do uso do T-test. A amostra foi composta por 272 estudantes, sendo 28,2% (n=77) homens e 71,4% mulheres (n=195); selecionados da área de ciências sociais (n=137; 50,2%), e da área de ciências da saúde (n=136; 49,8%). O álcool foi a droga mais utilizada (n=217; 79,8%), seguida da maconha (n=72; 26,6%) e, finalmente, a cocaína (n=3; 1.1%) nos últimos 12 meses. Conclusão: os resultados demostram que não existe relação significativa entre tais variáveis, e são importantes no nível das políticas de drogas para apoiar o desenvolvimento de novas estratégias preventivas para o uso de drogas.

RESUMEN Objetivo: determinar la relación entre conocimiento de consecuencias y uso de drogas en estudiantes de pregrado de una universidad en San José, Costa Rica. Método: el estudio, de corte transversal, examina el perfil demográfico de la muestra y la relación entre conocimiento de consecuencias, uso de drogas y rendimiento académico. El estudio se enfoca en tres tipos de droga: alcohol, marihuana y cocaína. Se analizarán tres variables: datos demográficos, conocimiento de consecuencias y uso de drogas. Resultados: la relación entre conocimiento de consecuencias y uso de drogas se realizó mediante el uso de la prueba T-test. La muestra fue de 272 estudiantes, con un 28.2% (n=77) de hombres y 71.4% de mujeres (n=195); seleccionados de las áreas de ciencias sociales (n=137; 50.2%), y del área de ciencias de la salud (n=136; 49.8%). El alcohol fue la droga más utilizada (n=217; 79.8%), seguida por marihuana (n=72; 26.6%) y finalmente la cocaína (n=3; 1.1%) en los últimos 12 meses. Conclusion: los resultados mostrados indican que no hay una relación significativa entre tales variables. Los hallazgos son importantes a nivel de políticas de drogas para apoyar el desarrollar de nuevas estrategias preventivas de uso de drogas.

Estudio Transversal: Consumo de Sustancias Psicotrópicas en Pacientes que Acuden al Servicio de Psicología del Centro de Salud No 1 de Azogues - Ecuador, 2017 / Cross ­ Sectional Research: Consumption of psychotropic substances in Psychology service patients´ of the Health Center No. 1 of Azogues, 2017

INTRODUCCIÓN: El consumo de sustancias psicotrópicas de manera continua actúan sobre el sistema nervioso central, estimulando o deprimiéndolo. Los objetivos del estudio fueron determinar la prevalencia del consumo de sustancias psicotrópicas en pacientes que acuden al servicio de Psicología, establecer cuáles son los psicotrópicos que se consumen, su frecuencia, su asociación con edad y sexo e identificar riesgo. MÉTODOS: Se trata de un estudio transversal, con un universo de 1182 pacientes, obtenidos del registro diario automatizado de consultas y atenciones médicas ambulatorias del Ministerio de Salud Pública, que midió la prevalencia del consumo de psicotrópicos en el área de Psicología del centro de salud No 1 de Azogues ­ Ecuador, durante el año 2017. Se utilizó la clasificación internacional de enfermedades 10 para los respectivos diagnósticos y se tabuló en los programas estadísticos SPSS versión 22 y EPIDAT 3.1. RESULTADOS: El 52.2 % eran hombres, la media de edad fue de 26 años. Se estableció una prevalencia de 9 % para el consumo de sustancias psicotrópicas. Los psicotrópicos más consumidos fueron: alcohol (3.6 %), cannabinoides (2.9 %) y múltiples drogas (1.8 %), teniendo más frecuencia de consumo, el sexo masculino (15.4 % frente a 1.9 % del femenino) y en el grupo etario de 10 - 19 años con un 13.9 %, seguido de los de 20 ­ 29 años con 11.1%. El uso nocivo tuvo una prevalencia de 57.55 %, la dependencia 34.9 % y la abstinencia un 7.55 %. CONCLUSIONES: Existe asociación estadística entre el consumo y las variables sexo y edad (ambas P: 0.000). El sexo masculino y ser adolescente/joven (10 ­ 29 años) constituyen factores de riesgo para el consumo de sustancias psicotrópicas (RP 7.9; LC: 4.2 ­ 14.6 y RP 2.5; LC: 1.6 ­ 3.7 respectivamente).

BACKGROUND: The consumption of psychotropic substances acts continuously on the central nervous system, stimulating or depressing it. The aim of the study they should determine the prevalence of use of psychotropic substances in patients who attended the psychology service, establish which psychotropic drugs are consumed, their frequency, their association with age and sex, and identify the risk. METHODS:It is a cross-sectional study, with a universe of 1182 patients, obtained of the automated daily record of outpatient consultations and medical attentions of the Ministry of Public Health, which measured the prevalence of psychotropic use in the area of Psychology of the health center Nº 1 of Azogues - Ecuador, during the year 2017. It was used the international classification of diseases 10 for the respective diagnoses and it was tabulated in the statistical programs SPSS version 22 and EPIDAT 3.1. RESULTS: The 52.2 % were men, the average age was 26 years. A prevalence of 9 % was established for the consumption of psychotropic substances. The psychotropics most consumed were: alcohol (3.6 %), cannabinoids (2.9 %) and multiple drugs (1.8 %), having more frequency of consumption, the male sex (15.4 % versus 1.9 % of the female) and in the age group of 10 -19 years with 13.9 %, followed by those aged 20 - 29 with 11.1 %. Harmful use had a prevalence of 57.55 %, dependence 34.9 % and abstinence a 7.55 %. CONCLUSIONS: There was a statistical association between consumption and sex and age variables (both P: < 0.001). Male and adolescent / young (10 - 29 years) are risk factors for the consumption of psychotropic substances (RP 7.9, LC: 4.2 - 14.6 and RP 2.5; LC: 1.6 - 3.7 respectively).

Farmacovigilancia en pacientes con el virus de inmunodeficiencia humana/sida en un hospital de Zimbabwe / Drug surveillance in patients with HIV/AIDS in a hospital of Zimbabwe

Se realizó un estudio descriptivo y prospectivo de 171 pacientes con virus de inmunodeficiencia humana/sida, tratados con antirretrovirales desde abril hasta diciembre de 2008 en el Hospital de Bindura de la provincia de Mashonaland Central (Zimbabwe), a fin de evaluar las reacciones adversas a estos fármacos. Los integrantes de la casuística recibieron combinaciones de dosis fijas y triples de medicamentos prescritos para combatir ese proceso morboso. Se encontró que el sexo femenino fue el más afectado, que 13,4 % experimentaron efectos medicamentosos no deseados y que la mayoría de las reacciones adversas fueron de causalidad probable y de significación clínica moderada. El personal farmacéutico desempeña una función importante en el seguimiento terapéutico de estos portadores.

A descriptive and prospective study was conducted in 171 patients with HIV/AIDS treated with antiretroviral drugs from April to December 2008 in Bindura Hospital of Central Mashonaland province (Zimbabwe), in order to evaluate the adverse reactions to these drugs. Patients of the case material received combinations of fixed and triple doses of medications prescribed to control the disease process. It was found that females were the most affected, 13,4 % experienced undesirable drug effects and most adverse reactions were of probable causation and moderate clinical significance. The pharmacy staff play an important role in therapeutic follow up of these carriers.

Pharmacological immunomodulation enhances peripheral nerve regeneration

To assess the effect of N-Acetylmuramyl-L-Alanyl-D-Isoglutamine MDP topically administrated on the regenerating peripheral neurons, twelve male C57BL/6J adult mice were equally distributed into three groups. Four mice underwent unilateral sciatic nerve transection and polyethylene tubulization, with a 4mm gap between the proximal and distal nerve stumps and were implanted with collagen + PBS (COL). Other four animals underwent the same surgical procedure but received collagen + MDP (COL/MDP) inside the prosthesis. Four animals were not operated and served as control group (NOR). After 4 weeks, the regenerated nerve cables were processed for total myelinated axon counting and myelinated fiber diameter measurement. The L5 dorsal root ganglion (DRG) was also removed and sectioned for sensory neurons counting and measurement. The results revealed significant difference (p<0.05) in axonal counting among the groups NOR (4,355±32), COL (1,869±289) and COL/MDP (2,430±223). There was a significant reduction in the axonal diameter in the operated groups (COL=3.38µm±1.16 and COL/MDP=3.54µm±1.16) compared to NOR (6.19µm±2.45). No difference was found in the number of DRG neurons between the experimental groups (COL=564±51; COL/MDP=514±56), which presented fewer sensory neurons compared to NOR (1,097±142). Data obtained indicate that locally applied MDP stimulates peripheral nerve regeneration in mice.

Para avaliar o efeito do NAcetilmuramil- L-Alanil-D-Isoglutamina administrado topicamente em neurônios periféricos em regeneração, doze camundongos C57BL/6J machos adultos foram igualmente separados em três grupos. Quatro animais sofreram transecção unilateral do nervo ciático que foi ancorado no interior de um tubo de polietileno, mantendo-se 4 mm de distância entre as extremidades dos nervos e receberam colágeno + PBS (COL) dentro do tubo. Outros quatro animais sofreram o mesmo procedimento cirúrgico, porém receberam colágeno + MDP (COL/MDP) no interior da prótese. Quatro animais não foram operados e serviram como controle de normalidade (NOR). Após quatro semanas, os cabos de regeneração foram coletados para determinação do número de axônios mielínicos e da mêdia do diâmetro das fibras mielínicas regeneradas. O gânglio da raiz dorsal L5 também foi coletado para contagem e mensuração dos neurônios sensitivos. Os resultados revelaram diferença significativa no número de axônios entre os grupos NOR (4355±32), COL (1869±289) e COL/MDP (2430±223). Houve redução significativa no diâmetro das fibras mielínicas nos grupos que receberam as próteses tubulares (COL=3,38µm±1,16 e COL/ MDP=3,54µm±1,16) quando comparados ao grupo NOR (6,19µm±2,45). O número de neurônios não diferiu entre os grupos experimentais (COL=564±51 e COL/MDP=514±56), os quais apresentaram menor número de neurônios sensitivos em relação ao grupo não operado (NOR=1097±142). Os dados obtidos indicam que a aplicação local do MDP estimula a regeneração de nervos em camundongos.