Synthesis, and anti-inflammatory activities of gentiopicroside derivatives / 中国天然药物

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Perfil de riesgo de los antidepresivos inhibidores selectivos de la recaptación de serotonina (ISRS) / Risk profile of antidepressants selective reuptake inhibitors (SSRIs)

Los antidepresivos inhibidores selectivos de la recaptación de serotonina son ampliamente utilizados en la práctica clínica y han desplazado a otros grupos de antidepresivos en las últimas décadas. Esto parece estar vinculado al concepto de su mayor perfil de seguridad y a la minimización de los potenciales efectos adversos que su uso podría generar. Sin embargo el número de efectos adversos tanto leves como graves reportados no son despreciables y es importante su conocimiento con el fin de evitar o diagnosticar en forma precoz y actuar en consecuencia

Selective serotonin receptor inhibitor are widely used in clinical practice and have moved to other antidepressive drugs in recent decades. This seems to be linked to the concept of their greater safety profile and to minimize potential adverse effects that their use could generate. However, the number of both minor and serious reported adverse effects are not negligible and knowledge is important in order to prevent or diagnose early and act accordingly

Efecto de una combinación nutritiva y selectiva con sustratos cromogénicos para diagnóstico de cocos grampositivos / Effect of a selective nutrient combination of chromogenic substrates for diagnosis of Grampositive cocci

INTRODUCCIÓN: la reemergencia de infecciones por bacterias grampositivas y el aumento de su patogenicidad, requiere de un diagnóstico microbiológico rápido y certero. En BioCen se desarrolló una composición cromogénica para el aislamiento, cultivo y diferenciación rápida y presuntiva de microorganismos grampositivos por medio de reacciones cromogénicas específicas, donde las bacterias gramnegativas se encuentran inhibidas de manera parcial o total. OBJETIVO: evaluar el efecto de la combinación de bases nutritivas, inhibidores selectivos y sustratos cromogénicos para aumentar la selectivad y capacidad diferencial para especies de los géneros Enterococcus, Streptococcus y Staphylococcus de importancia clínica. MÉTODOS: se evaluaron 21 cepas microbianas de la American Type Culture Collection y 24 aislamientos clínicos de Streptococcus, Enterococcus y Staphylococcus y otros microorganismos gramnegativos. Se evaluaron diferentes combinaciones de bases nutritivas, acetato de talio, ácido nalidíxico y sustratos cromogénicos para la promoción del crecimiento y diferenciación de las bacterias grampositivas. Se evaluó la funcionalidad microbiológica y se le determinaron los parámetros de calidad diagnóstica. RESULTADOS: la combinación de bases nutritivas permitió el desarrollo de los microorganismos grampositivos, en 24 h y su diferenciación por reacciones cromogénicas específicas. El crecimiento de los microorganismos gramnegativos fue inhibido por la acción del acetato de talio (0,014 g·L-1) y ácido nalidíxico (0,008 g·L-1), excepto Proteus mirabilis y Pseudomonas aeruginosa, cuyas características morfológicas no interfieren en la diferenciación de los microorganismos diana. La sensibilidad, especificidad y exactitud diagnósticas fueron del 100 %. CONCLUSIÓN: la combinación de las bases nutritivas, los inhibidores selectivos y los sustratos cromogénicos permitió el desarrollo y diferenciación de especies de los microorganismos evaluados. La inoculación en el medio cromogénico de microorganismos diana y no diana y la diferenciación de aquellas cepas donde se detectó color similar de las colonias por medio de pruebas complementarias rápidas, le confirió al medio elevadas sensibilidad, especificidad y exactitud diagnóstica.

INTRODUCTION: reemergence of Grampositive bacteria infections and the rise of their pathogenicity require a quick and accurate microbiological diagnosis. BioCen has developed a chromogenic composition for isolation, culturing and rapid and presumptive differentiation of gram-positive microorganisms through specific chromogenic reactions in which the inhibition of gramnegative bacteria is partial or total. OBJECTIVE: to evaluate the effect of a combination of nutrient bases, selective inhibitors and chromogenic substrates to increase the selectivity and differential capacity to detect Enterococcus, Streptococcus and Staphylococcus species of clinical importance. METHODS: twenty one microbial strains from the American Type Culture Collection and 24 clinical isolates of Enterococcus, Streptococcus and Staphylococcus and of other gramnegative microorganisms were evaluated. Various combinations of nutrient bases, thallium acetate, nalidixic acid and chromogenic substrates were also assessed for the promotion, growth and differentiation of grampositive bacteria. The microbiological functionality was evaluated whereas the diagnostic quality parameters were determined. RESULTS: the combination of nutrient bases allowed the development of grampositive microorganisms in 24 hours and their differentiation through specific chromogenic reactions. The growth of gramnegative microorganisms was inhibited by the thallium acetate (0.014 g·L-1) and nalidixic acid (0,008 g·L-1) except for Proteus mirabilis and Pseudomonas aeruginosa whose morphological characteristics do not interfere with differentiation of target microorganisms. Sensitivity, specificity and accuracy for diagnosis were 100 %. CONCLUSIONS: the combination of nutrient bases, selective inhibitors and chromogenic substrates allowed the development and differentiation of the evaluated microorganism species. The inoculation of target and non-target microorganisms in the chromogenic medium and the differentiation of those strains where a similar color of the colonies was detected by means of supplementary rapid tests provided the medium with high diagnostic sensitivity, specificity and accuracy.

Effects of cyclooxygenase-2 selective inhibitor Celecoxib on the expression of P-glycoprotein in rat with status epilepticus / 中华实用儿科临床杂志

Objective To study the effect of cyclooxygenase-2 (COX-2)selective inhibitor Celecoxib on the expression of P-glycoprotein(P-gp)in the brain of rats with status epilepficus,in order to assess the therapeutic value of intractable epilepsy.Methods Sixty adult male SD rats were randomly divided into blank control group,the epilepsy model group and Celecoxib intervention group.The status epilepticus was induced in rats by injecting Lithium pilocarpine.Forty-eight rats were included in the experiment.There were 16 rats in each of the blank control group,epilepsy model group and Celecoxib intervention group,respectively.Immunohistochemical method and Western blot method were used to detect the expression of P-gp in experimental group in the frontal cortex and hippocampus.Results Immunohistochemistry result showed that the expression of P-gp was significantly higher in epilepsy model group than the blank control group,and the difference was statistically significant (P ＜ 0.01);The P-gp expression in the Celecoxib intervention group was lower than that in the epilepsy model group,and the difference was statistically significant (P ＜0.01).Western blot results suggested that the expression of P-gp could be found both in the frontal cortex and hippocampus in each group.Compared with the blank control group,the P-gp expression was significantly higher than that in the epilepsy model group,and the expression of the P-gp was lower after the Celecoxib intervention than that in the epilepsy model group,and the difference was statistically significant (P ＜ 0.05).Conclusions COX-2 inhibitor Celecoxib could decrease the expression of P-gp in brain tissue with status epilepticus,which may provide a new method for the treatment of intractable epilepsy.

Ejaculação precoce: revisão de literatura sobre novos tratamentos / Premature ejaculation: a literature review about new treatment options

Ejaculação precoce é o problema sexual masculino mais comum, com prevalência de 2% a 23%. Este estudo é uma revisão do tratamento de ejaculação precoce em artigos de relevância publicados nas bases de dados PubMed, Lilacs e SciELO no período de 2006 a 2012. Discute-se sobre abordagens tópicas, medicações por via oral, acupuntura e drogas injetáveis. Os resultados mostram que a ejaculação precoce é problema de origem multifatorial e que diversos estudos estão sendo conduzidos sobre abordagens terapêuticas diferentes. O acompanhamento em longo prazo é fundamental para o tratamento e, em alguns casos, é importante que se realize terapia combinada. Ressalta-se que se deve aguardar os resultados de estudos que estão sendo desenvolvidos com novas drogas e terapias. Enquanto não houver novas conclusões, deve-se utilizar terapia medicamentosa por via oral e, em casos selecionados, terapia tópica.

Premature ejaculation is the most common sexual problem in men, with prevalence from 2% to 23%. This study is a review of relevant articles about the treatment of premature ejaculation published in the PubMed, Lilacs and SciELO databases between 2006 and 2012. We discuss topical approaches, oral medication, acupuncture and injectable drugs. The results of this study show that premature ejaculation is a multifactorial problem. In fact, many studies are being conducted on different therapeutic approaches to treat this condition. Long term follow-up is critical to treatment and, in some cases, combined therapy is important. We emphasize the relevance of waiting for the results of studies that are being conducted about new drugs and therapies. Oral medication and, in special cases, topical drugs, should be used while new conclusions are not reached.

CHANGE OF COX-1/2 EXPRESSION IN BRAIN AFTER SPARED NERVE INJURY-INDUCED NEUROPATHIC PAIN AND ANALGESIC EFFECTS OF COX INHIBITORS WITH DIFFERENT SELECTIVITY / 神经解剖学杂志

To observe the expression of cyclooxygenase (COX)-1 and COX-2 in brain after spared nerve injury (SNI) and compare the analgesic effects of COX inhibitors with different selectivity. Radioimmunoassay, RT-PCR and Western blotting techniques were used to evaluate the change of brain COX expression at different time points( before SNI, 1 h, 12 h, 1 d, 3 d, 7 d, 14 d, 30 d and 60 d after SNI); By exploring hot plate test, we observed the reacting time of animals after injection of saline, NS-398, SC-560 and indomethacin at different time points. The results showed that: ( 1 ) The expression of brain COX-1 didn't increase significantly until 14 d after SNI, while that of COX-2 increased significantly and rapidly after SNI and reached peak at the time point of 1 d ( all P ＜0.05 ); (2) NS-398 showed significant analgesic effect on neuropathic pain after SNI at the early phase ( P ＜ 0.05 ), but didn't persist for over 30 d; ( 3 ) Indomethacin and SC-560 didn't show significant analgesic effects until 14 d. These results suggest that brain COX-1 is involved in the late phase of neuropathic pain and may play a role in the persistence of pain, while brain COX-2 is involved in the early phase of neuropathic pain and may play a role in the pain origination.