The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 micromol/L), gp120 (500 pmol/L) plus ddC (50 micromol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 micromol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 micromol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 microm), whereas ddC mainly affected small diameter DRG neurons (< or =25 microm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning.</p><p><b>METHODS</b>In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope.</p><p><b>RESULTS</b>Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4 h or 30 h and tested on the 7th day after exposure, DDC group administrated at 30h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P < 0.05 or P < 0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone, DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels.</p><p><b>CONCLUSION</b>The results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.</p>

Efficacy and safety of zidovudine and zalcitabine combined with a combination of herbs in the treatment of HIV-infected Thai patients.

A randomized double blind placebo controlled trial to determine the efficacy and safety of combined-herbs (SH) given with zidovudine (ZDV) and zalcitabine (ddC) for the treatment of HIV infection in Thai adults was conducted in 3 hospitals in northern Thailand during 2002 to 2003. The eligible subjects were HIV-infected Thai adults who had never received anti-retrovirals, had a Karnofski Performance Score (KPS) of > or = 70, and had no opportunistic infections. The subjects were randomized to receive either a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and SH 2.5 g three times per day or a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and placebo 2.5 g three times per day for 24 weeks. The main outcome measures were HIV-RNA, CD4 cells, and blood chemistry profiles prior to the treatment and then every 4 weeks for 24 weeks. The baseline characteristics of 60 evaluable subjects, 40 in the SH group and 20 in the placebo group, were not significantly different. HIV RNA at week 4 and thereafter was significantly decreased from the baseline value in both groups (p<0.001). However, the decline in HIV RNA in the SH group was significantly more than that in the placebo group. The CD4 cells in the SH group at week 12 and thereafter were significantly increased from the baseline value. Serious adverse events in the two groups were not observed. It is concluded that an addition of SH herbs to two nucleoside reverse transcriptase inhibitors has greater antiviral activity than antiretrovirals only. The SH herbs may be an alternative for the third anti-retroviral agent in the triple drug regimen for the treatment of HIV infected patients in countries with limited resources.

Antirretrovirales. Realidades y limitaciones / Antiretrovirals. Realities and limitations

En el contexto de la investigación actual de la infección por VIH, los antirretrovirales ocupan un lugar preponderante. La síntesis de nuevos fármacos y el descubrimiento de resistencias virales ha provocado la creación de terapéuticas combinadas más agresivas contra el virus y, a su vez, más efectivas para limitar dichas resistencias. La valoración de la efectividad de los antivirales se realiza por dos métodos actualmente catalogados como indicadores de la progresión o limitación de la infección por el VIH: conteo de linfocitos CD4 y determinación de copias de RNA viral en plasma (carga viral). Gracias a éstos se puede determinar la necesidad de terapéuticas únicas o combinadas y limitar el daño provocado por el virus y evitar la progresión a SIDA

Documento de consenso sobre terapia antiretroviral em adultos / Retroviridae infection therapy in adults

Revisäo das recomendaçöes para terapia antiretroviral publicadas pelo Ministério da Saúde em 1994. Estas recomendaçöes baseavam-se no tratamento inaugural com zidovudina (AZT), e admitiam terapia combinada [AZT + didanosina (ddl), ou AZT + zalcitabina (ddC)] diante da falha da monoterapia inicial.

Avances recientes en terapia antirretroviral / Recent developments in antiretroviral therapy

Camios recientes en nuestro conocimiento acerca de la patogénesis de la infección causada por el virus de la inmunodeficiencia humana (VIH) en pacientes con el síndrome de inmunodeficiencia adquirida (SIDA) nos han llevado a repensar nuestras estrategias de tratamiento. Existe marcado interés en explorar el uso de medicamentos antirretrovirales en combinación. En esta revisión se presenta la información más reciente acerca de los resultados de estudios clínicos comparando monoterapia versus terapia combinada, incluyendo ACTG 175, los estudios DELTA y los estudios NUCA. Se presenta además información preliminar acerca del uso de los inhibidores de proteasa, una nueva familia de medicamentos antirretrovirales, incluyendo ejemplos de nuestra casuística

Tratamiento de la infección por el virus de la inmunodeficiencia humana (VIH): antirretrovirales / Treatment of HIV infections: antirretrovirals

Aunque no hay tratamiento curativo para la infección por virus de la inmunodeficiencia humana (VIH), los antirretrovirales son efectivos en cuanto a mejorar la calidad de vida, disminuyendo la frecuencia de infecciones oportunistas. Hay total acuerdo en indicarlos a aquellos pacientes en estadío SIDA, o severamente inmunodeprimidos. Se aconseja también su administración temprana cuando la población de linfocitos T4 está en <= 500 elementos/mm3, aunque los distintos grupos de estudio polemizan entre darlos a todos los infectados que alcancen ese nivel de linfocitos, independientemente de que sean sintomáticos o no, o esperar a que además tengan algún síntoma indicativo de la progresión al SIDA. Zidovudina continúa siendo la medicación de primera línea, reservándose zalcitabina y didanosina para cuando se manifiesten efectos de intolerancia, toxicidad o fracaso ante la primera

Zalcitabina / Zalcitabine

Revisao sucinta quimioterapico antiviral,contendo:emprego clinico,mecanismo de acao,farmacocinetica,efeitos adversos,precaucoes,contra-indicacoes,interacoes medicamentosas,associacoes farmacologicas e posologia.

Infecçäo pelo HIV / Infection HIV

A infecçao pelo HIV rapidamente ganhou importância no meio médico. Entretanto, ainda há desinformaçao sobre as manifestaçoes clínicas e a classificaçao dos pacientes. Os autores abordam os aspectos clínicos e epidemiológicos, com a nova classificaçao proposta pelo Center for Disease Control (CDC), em 1992, para o melhor manuseio da infecçao pelo HIV.

Didesoxicitidina y zidovudina secuenciales en infección avanzada por virus VIH-1: estudio fase II / Efficacy of sequential dideoxycytidine and zidovudine in stage IV HIV-1 infection: phase II study

Se estudiaron prospectivamente 17 pacientes infectados por VIH-1 tratados con ddC (0.375 mg tid durante 30 días), alternado con AZT (100 mg tid durante 30 días), por periodos de 8 a 32 semanas, medida de 17. Trece pacientes recibieron este tratamiento después de otros antirretrovirales, y cuatro lo recibieron desde el diagnóstico. Antes y después de AZT/ddC, la medida de células CD4 cambió de 184 a 164/uL (p NS), y la media de peso de 60 a 61 kg (p NS). Los parámetros hematológicos mejoraron en pacientes expuestos previamente a AZT. En uno de los cuatro casos desapareció la antigenemia P24 y en tres de nueve disminuyeron los niveles de beta-2-microglobulina sérica. En uno hubo neuropatía periférica sensorial reversible como efecto colateral de ddC y en ocho cedieron efectos adversos de AZT como intolerancia gástrica, cefalea y fiebre. La administración combinada secuencial de AZT/ddC fue bien tolerada y se disminuyó la toxicidad de AZT.