Sinopsis de revisiones sistemáticas sobre el efecto clínico de la Ketamina en el paciente agitado / Synopsis of systematic reviews on the clinical effect of Ketamine in the agitatedpatient / Sinopse de revisões sistemáticas sobre o efeito clínico da Ketamina no paciente agitado

Introducción:La literatura científica reporta estudios sobre la Ketamina, con alta heterogeneidad en los diseños, poblaciones, desenlaces y especialidades clínicas; sin embargo, no se encontró un documento que consolidara sistemáticamente la evidencia disponible y que oriente decisiones clínicas para el paciente agitado.Objetivo:Analizar la evidencia disponible en revisiones sistemáticas sobre el uso de Ketamina en paciente agitado. Materiales y métodos:Búsqueda sistemática en bases de datos multidisciplinarias. Se garantizó la exhaustividad del protocolo de búsqueda y selección de estudios, reproducibilidad y evaluación de la calidad metodológica según la herramienta Ameasurement Tool to Assess Systematic Reviews-2.Se realizó síntesis cualitativa de variables extraídas y estimación de proporciones con IC=95%.Resultados:Se tamizaron 134 estudios, 10 cumplieron los criterios del protocolo. Las revisiones sistemáticas incluyeron una población de 26.936 pacientes, la evidencia procede de dos series de caso, 7 estudios observacionales y 9 ensayos clínicos controlados. La Ketamina produce múltiples efectos adversos, algunos mayores a los causados por Midazolam.Conclusión:En algunos subgrupos se presentó alta proporción de efectos adversos respiratorios, neuropsiquiátricos y cardiovasculares, pero sin posibilidades de generalización a otros contextos. Es necesario mejorar la evidencia clínica y epidemiológica para la prescripción de Ketamina en el manejo de la agitación.

Introduction:The scientific literature about Ketamine use shows high heterogeneity in terms of design, populations, outcomes, and clinical specialties. Nevertheless, available evidence systematically consolidated to guide clinical decisions for anxious patients was notfound. Objective:To analyze evidence available in systematic reviews about the use of Ketamine in anxious patients. Materials and methods:Systematic search in multidisciplinary databases. The "A measurement Tool to Assess Systematic Reviews-2" was used to guarantee comprehensiveness of the searching protocol and study selection, reproducibility, and analysis of the methodological quality. A quantitative synthesis of the extracted variables and proportion estimation with a 95% CI were performed. Results:10 out of 134 screened studies met the protocol criteria. The systematic reviews included a population of 26,936 patients and the evidence comes mainly from two case series, 7 observational studies, and 9 controlled clinical trials. Ketamine has multiple adverse effects, some of them more critical than those caused by Midazolam. Conclusion:Some patient subgroups showed a high frequency of adverse effects such as respiratory, neuropsychiatric, and cardiovascular dysfunctions, but it was difficult to generalize them to other contexts. It is necessary to improve clinical and epidemiological evidence in order to prescribe Ketamine to manage anxiety.

Introdução:A literatura científica relata estudos sobre Ketamina, com elevada heterogeneidade nos desenhos, populações, resultados e especialidades clínicas; no entanto, não foi encontrado nenhum documento que consolide sistematicamente as evidências disponíveis e que oriente às decisões clínicas para o paciente agitado. Objetivo:Analisar as evidências disponíveis em revisões sistemáticas sobre o uso da Ketaminaem pacientes agitadose/ou agressivos. Materiais e métodos:Pesquisa sistemática em bases de dados multidisciplinares. A exaustividade do protocolo de pesquisae seleção dos estudos, reprodutibilidade e avaliação da qualidade metodológica foram garantidos com a ferramenta Ameasurement Tool to Assess Systematic Reviews-2. Foi realizada uma síntese qualitativa das variáveis extraídas e estimativa de proporções com IC=95 %. Resultados:134 estudos foram selecionados, 10 preencheram os critérios do protocolo. As revisões sistemáticas incluíram uma população de 26.936 pacientes,a evidência vem de duas séries de casos, 7 estudos observacionais e 9 ensaios clínicos controlados. A Ketaminaproduz múltiplos efeitos adversos, alguns maiores que os causados pelo Midazolam. Conclusão:Em alguns subgrupos houve alta proporção de efeitos adversos respiratórios, neuropsiquiátricos e cardiovasculares, mas sem possibilidade de generalização para outros contextos. É necessário melhorar as evidências clínicas e epidemiológicas para a prescriçãoda Ketaminano manejo da agitação.

Role of Reactive Oxygen Species in GDC-0152-Induced Apoptosis and Autophagy of NB4 cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of reactive oxygen species (ROS) on GDC-0152-induced apoptosis and autophagy of acute promyelocytic leukemia cell line NB4.@*METHODS@#Different concentrations of GDC-0152 combined with Z-VAD-FMK was applied to NB4 cells. Cell proliferation was detected by CCK8 method. Apoptosis rate, autophagy and ROS level were detected by flow cytometry. The autophagy was observed by Cyto-ID staining fluorescence microscopy, and flow cytometry were used to detect the fluorescence expression. The expression of autophagy-related protein LC3B was detected by Western blot.@*RESULTS@#GDC-0152 increased proliferation inhibition rate and apoptosis rate in NB4 cells (P＜0.05); GDC-0152 induced increase of ROS level of NB4 cells; GDC-0152 increased autophagy of NB4 cells that was found by Cyto-ID staining fluorescence microscopy and flow cytometry (P＜0.05). Western blot showed that GDC-0152 increased LC3B expression in NB4 cells and promoted the conversion of LC3BI to LC3BII; as compared with GDC-0152 (100 ng/ml), GDC-0152 (100 ng/ml) combined with ROS inhibitor YCG063 (10 μmol/L) decreased apoptosis and autophagy (P＜0.05).@*CONCLUSION@#GDC-0152 inhibits cell proliferation by inducing apoptosis and autophagy of NB4 cells. ROS can promote GDC-0152-induced apoptosis and autophagy of NB4 cells.

Essential oil from leaves of Myrcianthes fragrans (Myrtaceae) from Costa Rica: a new chemotype? / Aceite esencial de las hojas de Myrcianthes fragrans (Myrtaceae) de Costa Rica: ¿Un nuevo quimiotipo?

Myrcianthes is a Myrtaceous genus of flowering plants of about 30 to 40 species, distributed in the American continent. The aim of this work was to study the chemical composition of the foliar essential oil from M. fragrans growing wild in central Costa Rica. The essential oil was obtained through the steam distillation process in a Clevenger type apparatus. The chemical composition of the oil was performed by capillary gas chromatography with a flame detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS) using the retention indices on a DB-5 type capillary column in addition to mass spectral fragmentation patterns. A total of 98 compounds were identified, accounting for 98.8% of the total amount of the oil. The major constituents in the leaf oil were (E)-methyl cinnamate (39.6%), limonene (34.6%), α-pinene (6.8%), and linalool (6.8%). This is the first report of (E)-methyl cinnamate occurring in oils of this plant genus. These findings appear to suggest a new chemotype of M. fragrans.

Myrcianthes (Myrtaceae) consta de 30 a 40 especies, distribuidas en el continente americano. El objetivo del presente trabajo consistió en identificar la composición química del aceite esencial contenido en las hojas de M. fragrans, planta que crece en forma silvestre en el Valle Central de Costa Rica. La extracción del aceite se efectuó mediante el método de hidrodestilación usando un equipo de Clevenger modificado. La composición química del aceite se analizó mediante las técnicas de cromatografía gaseoso-líquida con detector de ionización de llama (GC-FID) y de cromatografía gaseoso-líquida acoplada a un detector de masas (GC-MS). Se utilizaron índices de retención obtenidos en una columna capilar tipo DB-5 y se compararon con los patrones de iones de fragmentación de masas. Se identificaron en total 98 compuestos, correspondientes a un 98.8% de los constituyentes totales. Los componentes mayoritarios del aceite resultaron ser (E)-cinamato de metilo (39.6%), limoneno (34.6%), α-pineno (6.8%) y linalol (6.8%). Este es el primer informe de la aparición de (E)-cinamato de metilo en aceite de hojas de este género de plantas. Los datos obtenidos parecen sugerir un nuevo quimiotipo de M. fragrans.

Derivatives of 3H-spiro1-benzofuran-2, 1’-cyclohexanes: immunostimulants for veterinary use / Derivados de 3H-espiro1-benzofurano-2, 1’-ciclohexanos: inmunoestimulantes de uso veterinario

Four 3H-spiro1-benzofuran-2, 1’-cyclohexanes were synthesized from filifolinol, two of which are reported for the first time. Docking molecular studies were carried out to determine in silico whether these derivatives have similar immunostimulant activity to that reported for filifolinol, and its oxidation product, filifolinone. Through of the study of interactions of these compounds with the heterodimer of the protein present in teleost TLR1-TLR2, filifolinol, 3’-filifolinchloride and filifolinyl acetate shows similar interactions between them, allowing to predict that they would have similar immunostimulant activity, but different to filifolinone and filifolinane or that they would act by a different mechanisms.

Cuatro 3H-spiro1-benzofuran-2, 1'-ciclohexanos se sintetizaron a partir de filifolinol, dos de los cuales son reportados por primera vez. Se llevaron a cabo estudios de docking molecular para determinar in silico si estos derivados tienen actividad inmunoestimulante similar a la reportada para filifolinol y su producto de oxidación, filifolinona. A través del estudio de las interacciones de estos compuestos con el heterodímero de la proteína presente en teleósteos TLR1-TLR2 se estableció que el filifolinol, 3'-cloruro de filifolinilo y acetato de filifolinilo tienen interacciones similares con el heterodímero, lo que permite predecir que entre ellos tendrían una actividad simi- lar, pero diferente a la de la filifolinona y filifolinano o que estos últimos actuarían por diferentes mecanismos.

Avaliação da atividade antibacteriana de extratos etanólico e de ciclohexano a partir das flores de camomila (Matricaria chamomilla L. ) / Evaluation of the antibacterial activity of ethanolic and cyclohexane extracts of chamomile flowers (Matricaria chamomilla L. )

Devido à crescente seleção de microrganismos resistentes aos antimicrobianos atuais, tem-se valorizado a busca por alternativas naturais. O presente estudo teve por objetivo avaliar a atividade antibacteriana de extratos etanólico e de ciclohexano de flores de camomila, espécie vegetal de uso antigo pela medicina tradicional, frente às bactérias ATCC Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli e Salmonella enterica subsp. enterica sorovar Typhimurium pelas técnicas de difusão em ágar e diluição em caldo. Foi observada inibição do crescimento de P. aeruginosa frente ao extrato etanólico bruto (1g/mL) na técnica de diluição em caldo, e confirmada pela técnica de difusão em ágar (halo de inibição de 10 mm de diâmetro). Para as demais bactérias testadas, os extratos e suas diluições não apresentaram efeito bacteriostático em nenhuma das técnicas. Pode-se concluir que o extrato etanólico bruto da camomila apresentou atividade antibacteriana frente à P. aeruginosa, porém não foi eficaz frente à S. aureus, E. coli e Salmonella enterica subsp. enterica sorovar Typhimurium. Portanto, são necessários novos estudos com diferentes linhagens de microrganismos, com o intuito de corroborar e assegurar os resultados apresentados, para definir o potencial antimicrobiano do extrato da camomila.

Due to the growing selection of microorganisms resistant to antimicrobial, the search for natural alternatives has become popular. The objective of the present study was to evaluate the antibacterial activity of ethanolic and cyclohexane extracts of chamomile flowers, a plant species long used by traditional medicine, against ATCC bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Salmonella enterica subsp. enterica serovar Typhimurium by agar diffusion and broth dilution techniques. Growth of P. aeruginosa was inhibited when crude ethanolic extract (1g/mL) was used broth dilution, and was confirmed by agar diffusion, (10 mm diameter inhibition zone). For the other bacteria tested, the extracts and their dilutions did not show any bacteriostatic effect in any of the techniques. It may be concluded that pure ethanolic extract of chamomile presents antibacterial action against P. aeruginosa, and none against S. aureus, E. coli e Salmonella enterica subsp. enterica sorovar Typhimurium. However, other studies with different strains of microorganisms may be useful in order to corroborate and ensure these results, to define evaluation of the antimicrobial activity of chamomile extract.

The Anti-calcification Effect of Dithiobispropionimidate, Carbodiimide and Ultraviolet Irradiation Cross-linking Compared to Glutaraldehyde in Rabbit Implantation Models

BACKGROUND: Glutaraldehyde (GA) is a widely used cross-linking agent for improving mechanical properties and resistance to enzymatic degradation of collagenous tissue, but it has several drawbacks such as calcification and cytotoxicity. The aim of this study was to find the alternative effective cross-linking methods to GA. MATERIALS AND METHODS: Bovine pericardium was processed with GA with ethanol+octanol and glycine detoxification, and polyethylene glycol (PG) space filler, dimethyl 3,3'-dithiobispropionimidate (DTBP), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) treatment, and the physical fixation of ultraviolet irradiation were done. The biologic material properties of variously treated pericardial tissues were assessed by biochemical, mechanical and histological tests. Treated pericardial tissues were also implanted subcutaneously or intramuscularly into the rabbit for 10 weeks to assess the xenoreactive antibody response of immunoglobulin G and M, their anti-calcification effect. RESULTS: The biochemical and mechanical properties of EDC fixed pericardial tissues were comparable to the GA fixed tissue. The cytotoxicity was lowest in space filler treated GA fixed group. In rabbit subcutaneous or intramuscular implantation models, decellularization, space filler, EDC treatment group showed significantly lower calcium content than GA only and DTBP treatment group (p<0.05, analysis of variance). The titer of anti Galalpha1-3Galbeta1-4GlcNAc-R antibodies did not change in the postimplantation serial enzyme-linked immunosorbent assay. Hematoxylin and eosin and von Kossa staining showed that decellularization, space filler, EDC, and ultraviolet treatment had less inflammatory cell infiltration and calcium deposits. CONCLUSION: The decellularization process, PG filler, and EDC treatments are good alternative cross-linking methods compared to GA only fixation and primary amine of DTBP treatment for cardiovascular xenograft preservation in terms of the collagen cross-linking stability and in vivo anti-calcification effects.

Repaglinide, but Not Nateglinide Administered Supraspinally and Spinally Exerts an Anti-Diabetic Action in D-Glucose Fed and Streptozotocin-Treated Mouse Models

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 microg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

A reduced grade of liver fibros-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use / Grado reducido de fibroesteatosis tras la administración de raltegravir, maraviroc y fosamprenavir en un paciente co-infectado de VIH/VHC con hepatitis crónica, cardiomiopatía, intolerancia al nelfinavir y un aumento pronunciado de los niveles de creatina fosfoquinasa sérica probablemente debido al uso del inhibidor de la integrasa

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

Experimental study of the anti-inflammatory and analgesic effects of diethyl 1,3-dicyclohexyl- 1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the anti-inflammatory and analgesic activities of diethyl 1,3-dicyclohexyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (ZL-5010) in vivo and in vitro.</p><p><b>METHODS</b>The analgesic effect of ZL-5010 was evaluated by acetic acid-induced writhing response in mice, and the anti-inflammatory effects was assessed in mice with xylene-induced ear edema and in rats with carrageenan-induced paw edema. Mouse peritoneal exudate cells activated by bacterial lipopolysaccharides (LPS) were used to evaluate the anti-inflammatory effect of ZL-5010 in vitro. The levels of interleukin-1β (IL -1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>At the doses of 0.25 and 0.5 mmol/kg, ZL-5010 administered by gavage once daily for 3 days significantly reduced acetic acid-induced writhing frequency and suppressed xylene-induced ear edema in mice, and alleviated paw edema induced by carrageenan in rats (P<0.05). The agent also inhibited the production of the pro-inflammatory cytokines IL-1β and TNF-α by LPS-induced mouse peritoneal exudate cells in vitro, with the statistically significant minimum effective concentrations of 10 and 20 µmol/L, respectively (P<0.05).</p><p><b>CONCLUSION</b>ZL-5010 administered by gavage has anti-inflammatory and analgesic effects in mice and rats, and in mouse peritoneal exudate cell cultures, the agent also inhibits the production of the pro-inflammatory cytokines IL-1β and TNF-α.</p>

Work Environments and Exposure to Hazardous Substances in Korean Tire Manufacturing

OBJECTIVES: The purpose of this study is to evaluate the tire manufacturing work environments extensively and to identify workers' exposure to hazardous substances in various work processes. METHODS: Personal air sampling was conducted to measure polycyclic aromatic hydrocarbons, carbon disulfide, 1,3-butadiene, styrene, methyl isobutyl ketone, methylcyclohexane, formaldehyde, sulfur dioxide, and rubber fume in tire manufacturing plants using the National Institute for Occupational Safety Health Manual of Analytical Methods. Noise, carbon monoxide, and heat stress exposure were evaluated using direct reading instruments. Past concentrations of rubber fume were assessed using regression analysis of total particulate data from 2003 to 2007, after identifying the correlation between the concentration of total particulate and rubber fume. RESULTS: Workers were exposed to rubber fume that exceeded 0.6 mg/m3, the maximum exposure limit of the UK, in curing and production management processes. Forty-seven percent of workers were exposed to noise levels exceeding 85 dBA. Workers in the production management process were exposed to 28.1degrees C (wet bulb globe temperature value, WBGT value) even when the outdoor atmosphere was 2.7degrees C (WBGT value). Exposures to other substances were below the limit of detection or under a tenth of the threshold limit values given by the American Conference of Governmental Industrial Hygienists. CONCLUSION: To better classify exposure groups and to improve work environments, examining closely at rubber fume components and temperature as risk indicators in tire manufacturing is recommended.

In vitro antiproliferative activity of 3 H-spiro [1-benzofuran-2,1'-cyclohexane] derivatives / Actividad antiproliferativa in vitro de derivados de 3 H-spiro [1-benzofuran-2, 1'-cyclohexano]

The in vitro effect of the resinous exudate of Heliotropium filifolium, of the 3 H-spiro[1-benzofuran-2,1 '-cyclohexane] derivative called filifolinol 1, isolated from the resin and the semi-synthetic compounds filifolinone 2 and filifolinoic acid 3, obtained from filifolinol 1, were evaluated on the proliferation of an immortalized cell line, UCHT1, derived from rat thyroid. We evaluated the effect of these compounds on UCHT1 cell growth parameters by calculating doubling time; and toxicity using the LIVE/DEAD™ in vitro test. The results showed that the resin is not active, while filifolinone 2, filifolinoic acid 3 and filifolinol 1 produced a significant inhibition of cell doubling time, in concentrations equal or greater than 50, 25 and 75 uM, respectively. The LIVE/DEAD test showed no significant toxicity at these concentrations, compared to cultures kept in absence of compounds. These results suggest a possible cytostatic effect of these compounds, and could therefore constitute potential alternatives for antineoplasic therapy.

Se evaluó el efecto in vitro de la resina aislada desde Heliotropium filifolium y del derivado 3 H-spiro[1-benzofuran-2,1'-cyclohexano] llamado filifolinol 1, obtenido desde este exudado resinoso y los compuestos semi-sintéticos filifolinona 2 y ácido filifolinoico 3, obtenidos a partir de filifolinol 1, sobre la proliferación de la línea celular inmortal, UCHT1, derivada de tumor de tiroide de rata. Evaluamos el efecto de estos compuestos en el desarrollo celular de UCHT1 a través de los parámetros tiempo de doblaje y citotoxicidad usando el test LIVE/DEAD™ in vitro. Los resultados mostraron que la resina no presentó actividad y que filifolinona, ácido filifolinoico y filifolinol producen una inhibición significativa del tiempo de doblaje celular, en concentraciones iguales o superiores a 50, 25 y 75 uM, respectivamente. El test LIVE/DEAD no mostró toxicidad significativa en comparación con los cultivos mantenidos en ausencia de compuestos. Estos resultados sugieren un posible efecto citostático de estos compuestos y por lo tanto, constituirían alternativas potenciales para terapia antineoplásica.

Toxicity of Methylcyclohexane and Its Effect on the Reproductive System in SD Rats

OBJECTIVES: There is limited data regarding the toxicity of methylcyclohexane, despite its wide use in rubber adhesives, paint diluents, and cleansing agents. This study aimed to verify the toxicity and influence on the reproductive system of methylcyclohexane after its repeated injection in Sprague Dawley (SD) rats. METHODS: Methylcyclohexane was injected subcutaneously into male and female SD rats once a day, five times a week, for 13 weeks at different doses (0, 10, 100, and 1,000 mg/kg/day) for each group. The toxicity of testing material was verified by observing the change in body and organ weight, hematological change, pathological findings, and effect on the reproductive system at each different concentration. RESULTS: In the 1,000 mg/kg/day group, there were cases of animal deaths. In animals that survived, hematological changes, including a decrease in the red blood cell count, were observed. A considerable weight gain or loss and pathological abnormalities in the liver, kidney, and other organs were found. However, the 10 and 100 mg/kg/day groups did not cause deaths or other specific abnormalities. In terms of reproductive toxicity, there were changes in hormone levels, including a significant decrease in hormones such as estradiol and progesterone (p < 0.001) in male animals. Menstrual cycle change for female animals did not show concentration dependency. CONCLUSION: When injected repeatedly for 13 weeks, methylcyclohexane proved to be toxic for the liver, heart, and kidney at a high dose. The absolute toxic dose was 1,000 mg/kg/day, while the no observed adverse effect level was less than 100 mg/kg/day. The substance exerted little influence on the reproductive system.

Water soluble fractions of caraway (Carum carvi L. ) essential oil / Fracción de aceite esencial de alcaravea (Carum carvi L. ) soluble en agua

Natural essential oils are used extensively in fragrances, flavorants, and in the food and pharmaceutical industries. During hydrodistillation, a part of the essential oil becomes dissolved in the condensate and lost as this water is discarded. In this study, carvone and limonene content recovered from hydrodistillation waste water of caraway fruit were quantified using two methods for recovering dissolved aromatic molecules from condensate water: extraction through distillation and extraction by means of a solvent. This allows for the conservation of useful molecules which are typically discarded with the waste water produced during the distillation process. The objective of this study was to quantify the carvone and limonene content recoverable from waste water derived from the distillation of caraway essential oil. The well-known Clevenger method and a simpler, more practical technique employing cyclohexane as a solvent were employed to determine the recoverable content of aromatic molecules from the hydrosol. The chemical compositions of the respective recovered extracts were compared with those of the primary oils to analyze the efficacy of these methods. Recovered extract accounted for 10 to 40 percent of the total oil yield. The limonene and carvone molecules recovered using these methods were quantified through gas chromatography in order to characterize the composition of the secondary extract produced.

Los aceites esenciales naturales se utilizan ampliamente en las fragancias, saborizantes, y en la industria alimentaria y farmacéutica. Durante la hidrodestilación, una parte del aceite esencial se disuelve en el condensado y se pierde como agua de descarga. En este estudio, el contenido de carvona y limoneno recuperados del agua de desecho de la hidrodestilación de la fruta de alcaravea se cuantificaron utilizando dos métodos para recuperar las moléculas aromáticas disueltas en el agua condensada: extracción a través de la destilación y la extracción con un disolvente. Esto permite la conservación de las moléculas útiles que normalmente son desechadas con las aguas residuales producidas durante el proceso de destilación. El objetivo de este estudio fue cuantificar el contenido de carvona y limoneno recuperable de las aguas residuales procedente de la destilación del aceite esencial de alcaravea. El conocido método de Clevenger y una técnica sencilla y práctica que emplea ciclohexano como disolvente fueron utilizadas para determinar el contenido de moléculas aromáticas contenidas en el hidrosol. La composición química de los extractos recuperados fue comparada con los aceites primarios para analizar la eficacia de estos métodos. El extracto recuperado representa del 10 al 40 por ciento del contenido total de aceite esencial. Las moléculas de limoneno y carvona recuperadas mediante estos métodos se cuantificaron mediante cromatografía de gases con el fin de caracterizar la composición del extracto secundario.

Inhibitory effects of TNP-470 in combination with BCNU on tumor growth of human glioblastoma xenografts / 华中科技大学学报（医学）（英德文版）

This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice. Human glioblastoma U-251 cells (1×10(7)) were injected into 24 nude mice subcutaneously. The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation: TNP-470 group, in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times; BCNU group, in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times; TNP-470 plus BCNU group, in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group; control group, in which the mice were given 0.2 mL of the mixture including 3% ethanol, 5% acacia and 0.9% saline subcutaneously every other day 7 times. The tumor size and weights were measured. The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105. The results showed that on the 21th day following treatment, the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm(3), markedly lower than that in the TNP-470 group [(576.10±114.29)mm(3)] and the BCNU group [(473.01±48.04)mm(3)] (both P<0.01). And the xenograft volume in these 3 treatment groups was even much lower than that in the control group [(1512.61±470.25) mm(3)] (all P<0.01). There was no significant difference in the volume of xenografts between the TNP-470 group and the BCNU group (P>0.05). The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%, notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P<0.01) on the 21th day following treatment. There was no significant difference in the inhibition rate of tumor growth between the TNP-470 group and the BCNU group (P>0.05). The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P<0.05). The MVD of xenografts in the 3 treatment groups was markedly reduced as compared with that in the control group (all P<0.05). No significant changes in weights were observed before and after the treatment in each group (all P>0.05). It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects.

HIV entry inhibitors: progress in development and application / 药学学报

This review discusses recent progress in the development of anti-HIV agents, with emphasis on small molecule HIV-1 entry inhibitors. The entry inhibitors primarily target HIV-1 envelope glycoproteins or the cellular receptors, CD4 and chemokine receptors. Two of the entry inhibitors, enfuvirtide and maraviroc, have been approved by the US FDA for AIDS therapy. The drug resistance associated with some of the entry inhibitors will also be discussed.

The newest developments in anti-HIV-1 drugs / 药学学报

In the two decades since AZT was first approved for clinical use in 1987, 24 additional antiretroviral agents have been approved. They include 7 nucleoside analogs, a nucleotide analog and 4 non-nucleoside reverse transcriptase inhibitors, 10 protease inhibitors, 2 entry inhibitors and an integrase inhibitor. More than 20 investigational agents are currently being studied in clinical trials. Highly active antiretroviral therapy (HAART), which involves a combination of anti-HIV-1 drugs, is extremely effective in suppressing HIV-1 replication and increasing CD4+ number and results in substantial reductions in HIV-1-related morbidity and mortality. In last 20 years, much has been learned about resistance to antiretroviral drugs, drug interactions and metabolic complications of antiviral drug use. Drugs are now selected on the basis of resistance tests and on the risk of specific drug complications in individual patients. As a result, decisions about the therapy of HIV/AIDS have become personalized and are made on a patient-by-patient basis. With appropriate medical management, a person with HIV-1 now has the possibility of a nearly normal life expectancy.

Composition and antibacterial activity of the volatile oils from different parts of Achillea tenuifolla Lam, from Iran

Achillea tenuifolia Lam. [Compositae] with small yellow flowers and several times pinnately divided leaves in worm shape is known for many years in the folk medicine. It has been used to reduce sweating and to stop bleeding. It helps regulation of the menstrual cycle and reduces heavy bleeding and pain. Plant material [flower, leaf and stem] was collected in Khalkhal-Ardabil road area, at an altitude of 1650 m in Northwest of Iran. Plant materials were air dried 150g of flower; 150g of leaf and 200g of stem were subjected to 3h of hydrodistillation in a Clevenger-type apparatus, separately. The hydrodistilled essential oils were analyzed by GC and GC/MS methods. Antibacterial activities of the oils were evaluated by the disc diffusion method using Mueller-Hinton agar for bacteria. The oil of flower was characterized by higher amount of limonene [23.2%] and alpha cadinol [18.2%]. Twenty one constituents representing [92.2%] of the leaf oil were identified of which limonene [25.2%], u-pinene [14.4%], caryophyllene oxide [6.5%], alpha-gurjunene [6.3%], bornyl acetate [5.5%] and delta-cadinene [4.4%] were major components. The main components of the stem oil were limonene [23.6%], alpha-pinene [13.4%] and spathulenol [6.4%]. The oils showed inhibitory effects on Escherichia coli and Salmonella typhi. The main components of the oil of flower, leaf and stem were limonene, alpha-cadinol, alpha-pinene and spathulenol, but Borneol, ornyl acetate, camphor, alpha and beta-thujone, and 1, 8-cineol were found as the main components of essential oils of many other Achillea species. These variations may be attributed mainly to variation in their agroclimatic and geographical conditions. The results indicated that three oils were found to be active against bacteria, the oil from the flower was found to be more active than the oil from the leaf and stem

Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats

Saffron is the dried stigmata of the flowers of saffron [Crocus sativus L., Iridaceae]. Saffron is well known for the treatment of gastric disorders in traditional medicine. In the search for new potential antiulcer agents, the effects of the ethanol extract of saffron and its active constituents crocin and safranal as compared with omeprazole against gastric ulcer induced by indomethacin in non-diabetic and streptozocin diabetic rats were studied. The effects of pretreatment with saffron extract [25, 100 or 250 mg/kg, p.o.], crocin [2.5, 5 or 10 mg/kg, p.o.] and safranal [0.25, 2, 5 ml/kg, p.o.] and omeprazole [30 mg/kg, p.o.] 30 min before administration of indomethacin [40 mg/kg, p.o. in non-diabetic rats and 15 mg/kg, p.o. in diabetic rats] on gastric lesions, increase of lipid peroxidation and decrease of glutathione levels induced by indomethacin in non-diabetic and diabetic rats were evaluated. Saffron extract, crocin, safranal and omeprazol prevented the gastric lesions, increase of lipid peroxidation and decrease of glutathione levels induced by indomethacin in non-diabetic and diabetic rats as compared with the control group [P < 0.01]. The effects of saffron extract, crocin and safranal on the gastric ulcer index, lipid peroxidation and glutathione levels were comparable to omeprazole. Saffron, crocin and safranal may prevent the gastric mucosa damage due to their antioxidant properties by increasing the gluthatione levels and diminishing the lipid peroxidation in the rat gastric mucosa

[ systematic review on pharmacology of saffron and its active constituents]

Saffron is the dried stigmata of the flowers of saffron [Crocus sativus L., Iridaceae]. Saffron has various pharmacological effects and is regarded as a potent drug. Thus research on the biological activities of saffron and its active constituents may have clinical and public health applications. To evaluate the basic and clinical pharmacology of saffron and its active constituents, the English papers in the data bases EMBASE, SCOPUS, MEDLINE, SCIENCE DIRECT, CHEMICAL ABSTRACTS, English and Persian papers in the data base SID and proceedings of the Iranian physiology and pharmacology congresses and Iranian congresses concerning saffron were retrieved by using keywords comprising Crocus sativus, anti-tumor, anti-oxidant, anti-genotoxic, memory, neuroprotective, analgesic, anticonvulsant, opioid dependence, antidepressant, cardiovascular, lipids, respiratory, gastric ulcer, immune system, ocular, antimicrobial and toxicity and their Persian equivalents from 1975 until November 2008. The investigations demonstrate that saffron and its active constituents have anti-tumor, anti-oxidant, anti-genotoxic, memory and learning enhancing, neuroprotective, analgesic and anti-inflammatory, anticonvulsant, opioid abstinence syndrome alleviating, antidepressant, hypotensive, hypolipidemic, insulin resistance reducing, tissues oxygenation enhancing, bronchodilator, antitussive, gastric ulcer preventive, Immune-stimulator, retina protective and antibacterial effects. In view of the existing deficiencies in the conducted researches, further clinical trials, pharmacokinetic and toxicological studies concerning saffron are recommended

Clinical evaluation of efficacy and safety of nateglinide in the treatment of type 2 diabetes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of nateglinide, a new antidiabetic agent, in the treatment of type 2 diabetes.</p><p><b>METHODS</b>A total of 219 treatment-naïve patients with type 2 diabetes from 6 centers were enrolled in this study and blindly divided into nateglinide group (n = 105) and repaglinide group (n = 114). In all patients, the disease was confirmed for at least three months. The whole observation lasted for 12 weeks. The efficacy indicators measured include glycohemoglobin A1c (HbA1c), fasting blood glucose, and 2 hours postprandial blood glucose, and the safety parameters measured included renal and hepatic function, serum lipids, and blood and urea profiles.</p><p><b>RESULTS</b>Similar decreases in fasting blood glucose, 2 hours postprandial blood glucose, and HbA1 c were found in both nateglinide group and repaglinide group without significant differences. No severe adverse events were noted. The hypoglycemia event reports were not significantly different between these two groups.</p><p><b>CONCLUSION</b>Nateglinide is an effective and safe drug in treating type 2 diabetes.</p>