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INTRODUCTION: To review the physiology of the glutamate receptor subunits such as N-methyl-D-aspartate (NMDA). DEVELOPMENT: Glutamic acid (Glu) is the major excitatory neurotransmitter in the central nervous system which interacts with two types classified into two types: metabotropic and ionotropic. Ionotropic receptors are classified according to the affinity of their specific agonists: N-methyl-D-aspartate (NMDA), α-amino acid-3-hydroxy-5-methyl-4-isoxazole (AMPA) and kainic acid (KA). NMDA receptors are macromolecular structures that are formed by different combinations of subunits, NMDAR1 (NR1), NMDAR2 (NR2) and NMDAR3 (NR3) CONCLUSIONS: The study of this receptor has been of great interest due to its role in synaptic plasticity, but mainly due to the permeability it has to Ca(++) ion. This review examines the molecular composition of NMDA receptor and the variants of NR1 subunit edition in association with NR2 subunit dimer, the main form of this receptor. The composition, structure and function and their distinct expression patterns in both time and space, has shown the versatility and diversity of functionally different isoforms of the NR1 subunit and various pharmacological properties of the NR2 subunit.
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Receptores de N-Metil-D-Aspartato/fisiologia , Relação Estrutura-AtividadeRESUMO
Hypoxia-inducible factor-1 alpha (HIF-1α) is a master transcription factor that regulates the response to hypoxia and ischemia and induces the expression of various genes, including vascular endothelial growth factor (VEGF) and erythropoietin (EPO). This study shows the systemic response of increased HIF-1α, EPO, and VEGF mRNA and protein. In addition, VEGF expression was increased in neurons and over-expressed in glial cells in a model of neuroexcitotoxicity in the hippocampus, in which rats were neonatally exposed to high glutamate concentrations. Simultaneous increases in HIF-1α, EPO and VEGF mRNA in peritoneal macrophages were also observed. Our study is consistent with the hypothesis that these genes exert a protective effect in response to neurotoxicity.
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Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipocampo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/metabolismo , Síndromes Neurotóxicas/patologia , Fatores Etários , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Eritropoetina/genética , Eritropoetina/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Macrófagos/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Síndromes Neurotóxicas/etiologia , Neurotoxinas/toxicidade , Gravidez , RNA Mensageiro , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVES: To describe the prevalence of baseline drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naïve patients from Mexico with established HIV-1 infection. METHODS: Resistance testing was performed on plasma samples from antiretroviral-naïve patients. Data on mutations associated with antiretroviral drug resistance were obtained using Stanford software (http://hivdb.stanford.edu). RESULTS: Ninety-six treatment-naïve individuals were enrolled in the study during 2002-2003. Of these, 83 patients (86%) had at least one resistance mutation and 15 (16%) had drug resistance. At baseline, the mean plasma viral load was 299 834 HIV-1 RNA copies/mL, and at follow-up it was 37 620 copies/mL (P<0.0001). Primary mutations in the reverse transcriptase region were observed in 15% of patients. For nucleoside inhibitors, mutations T215Y/C and F77L (3%) and D67N/S, T69N and M184V (2%), were detected. For nonnucleoside inhibitors, mutations K103N/R (6%), Y181C (3%) and G190A (2%) were detected. Overall, 6% of patients showed resistance to delavirdine and nevirapine, 4% to efavirenz, and 2% to lamivudine and nelfinavir. Twelve patients showed no response to treatment and three of these patients had antiretroviral drug resistance. CONCLUSIONS: The prevalence of baseline drug-resistance mutations found in this study was similar to that found in previous reports for newly HIV-infected individuals, although access to and management of antiretrovirals in Mexico are different.
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Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/genética , Mutação , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Protease de HIV/genética , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Masculino , Estudos Prospectivos , RNA Viral/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Resultado do Tratamento , Carga ViralRESUMO
Virend (SP-303), a new topical antiviral agent with activity against herpesvirus, was evaluated in a multicenter, double-blind, placebo-controlled Phase II study for safety and effectiveness against recurrent genital herpes lesions in patients with AIDS. The primary endpoints of this study were complete healing of lesions and time to healing. Patients had a history of recurrent genital or anogenital herpes with at least one lesion and positive HSV culture at enrollment. Participants received Virend (15% ointment; 24 patients) or matching placebo (21 patients) three times a day for 21 days. Excluding two patients in the Virend group who received an initial treatment but were lost to follow-up, 9 of 22 (41%) patients treated with Virend experienced complete healing of their lesions compared with three (14%) patients in the placebo group (P = 0.053). Viral culture revealed that 50% of Virend-treated patients and 19% of placebo-treated patients became culture-negative during treatment (P = 0.06). Based on these preliminary clinical findings, further evaluation of Virend for topical treatment of genital herpes in patients with AIDS is planned.
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Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/uso terapêutico , Doenças do Ânus/tratamento farmacológico , Biopolímeros/uso terapêutico , Catequina/análogos & derivados , Herpes Genital/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Administração Tópica , Adulto , Antivirais/efeitos adversos , Antivirais/química , Doenças do Ânus/induzido quimicamente , Doenças do Ânus/virologia , Biopolímeros/efeitos adversos , Biopolímeros/química , Catequina/efeitos adversos , Catequina/química , Catequina/uso terapêutico , Método Duplo-Cego , Feminino , Seguimentos , Herpes Genital/complicações , Herpes Genital/virologia , Herpes Simples/complicações , Herpes Simples/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Dor/tratamento farmacológico , Fatores de Tempo , Eliminação de Partículas ViraisRESUMO
Potassium iodide (KI), the specific treatment for sporotrichosis, apparently does not have a direct action on Sporothrix schenckii. The spontaneous healing and the variability of the clinical presentation in the disease have strengthened the idea that the KI rather interacts with the immune response of the host. The phagocytic process is inefficient in individuals with sporotrichosis in whom the microbicidal mechanism of halogenation fails to control the disease. There is evidence that blocking of free radicals decreases in the presence of KI. Humoral and cellular immunity are present in sporotrichosis but its participation is uncertain; it is yet to be determined if in this mycosis the KI influences other processes or factors of immune response.
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In México, since may 1986, the mandatory detection of antibodies against HIV in blood and derivates for the use by humans was legislated, one year later the prohibition of blood trade took effect. The impact of the Sanitary Normativity in the seroprevalence of anti HIV antibodies between blood donors one year before and one year after it took result was compared. A sample was taken from 4743 serums of donors of 6 blood banks in Guadalajara between june 1986 and june 1988; 4020 in the first year and 723 the next. In all the samples the presence of anti HIV antibodies was determined by the ELISA assay and the positive ones were confirmed by indirect immunofluorescence and by Western blot. During the first year, the seroprevalence fluctuated between 2.02 and 30.15 percent depending on different factors, differing from the second year where the seroprevalence was 0.14 percent. It is concluded that the mandatory detection of antibodies against HIV and the prohibition of blood trade, have been definitive factors to decrease the incidence of HIV in blood donors.
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Doadores de Sangue/legislação & jurisprudência , Soropositividade para HIV/epidemiologia , Soroprevalência de HIV , Adulto , Feminino , Humanos , Masculino , México/epidemiologia , Distribuição AleatóriaAssuntos
Hemólise/efeitos dos fármacos , Peróxido de Hidrogênio , Síndrome do Desconforto Respiratório do Recém-Nascido/sangue , Adulto , Líquido Amniótico/análise , Eritrócitos , Feminino , Sangue Fetal/citologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Surfactantes Pulmonares/análise , RiscoRESUMO
El proposito de este estudio fue investigar la posibilidad de efectuar una prueba con sangre del cordon umbilical que permitiera procedir cuales neonatos desarrollarian el sindrome de insuficiencia respiratoria neonatal (SIRN). Para ello se estudiaron 45 neonatos, de los que 30 fueron maduros y 15 inmaduros. En ellos se efectuo antenatalmente la prueba de la espuma (PE) en liquido amniotico y la prueba de la hemolisis de los eritrocitos con peroxido de hidrogeno (PH202).Los 30 neonatos maduros dieron la PE positiva y la PH202 de 7.55+/-7.30 por ciento, y ninguno desarrollo el SIRN. Los 15 inmaduros dieron la PE negativa, la PH202 de 41.23+/- 25.50 por ciento, y todos desarrollaron el SIRN. En nueve inmaduros que desarrollaron el SIRN y se recuperaron, la PH202 fue menor de 30 por ciento. En seis inmaduros que fallecieron por el SIRN, la PH202 fue mayor del 30 por ciento, y la PH202 y la PE tuvieron la misma certeza para pronosticar cuales neonatos desarrollarian el SIRN. Ademas, la PH202 permitio pronosticar la gravedad del sindrome
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Recém-Nascido , Humanos , Peróxido de Hidrogênio , Síndrome do Desconforto Respiratório do Recém-NascidoAssuntos
Hipertensão/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Hipertensão/terapia , Masculino , México , Pessoa de Meia-Idade , População RuralRESUMO
It has been reported that a great part of the deleterious effect caused by ionizing radiations is due to oxidative phenomena. The purpose of this work was to investigate if some antioxidants commonly used in the food industry might have a radioprotecting effect. N propyl-galate (NPG), hydroxyanisol-butylated (HAB) and hydroxytoluene-butylated (HTB) were utilized. Forty BALB/C mice that received 600 rads of gamma irradiation from a 60Co emitter died 17.12 +/- 7.82 days after. Thirteen mice that were injected 5 mg of NPG 24 hours and 30 minutes before radiation survived for more than 90 days. This same effect was observed in 13 mice that were also injected with 10 mg NPC and in other 13 that received 10 mg of HAB in the same way. Doses of 5 mg HAB or 5 and 10 mg HTB did not have a radioprotecting effect. When the radiation dose was increased to 800 rads, the radioprotecting effect was absent with any of the NPG, HAB or HTB doses. In protected mice, preservation of higher numbers of hematopoietic cells were observed in the bone marrow together with slight reduction of chromosomal fractures. There results show that antioxidants used in the food industry have a radioprotecting effect that had not been investigated.