Analgesic and side effects of intravenous recombinant Phα1ß

Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1ß exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1ß in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1ß using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1ß toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1ß may be feasible for drug-induced analgesia, without causing any severe side effects.(AU)

Analgesic and side effects of intravenous recombinant Ph alfa 1 beta

Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.

Papel do estresse oxidativo na fisiopatologia da esquizofrenia / Role of oxidative stress in the pathophysiology of schizophrenia

Introdução: a fisiopatologia da esquizofrenia é ainda pouco esclarecida. Vários estudos descrevem o importante papel da inflamação e do estresse oxidativo nessa explicação. Esquizofrênicos parecem ter seus mecanismos de defesa alterados e resposta distinta dos controles ao estresse oxidativo, que é lesivo a várias estruturas celulares, entre elas a matriz extracelular (MEC). Uma MEC íntegra e estruturada é essencialpara a boa condução sináptica. Objetivo: avaliar a resposta de genes que codificam proteínas da MEC ao estresse oxidativo em esquizofrênicos crônicos e controles. Metodologia: foi feita cultura de fibroblastos a partir de biópsias de pele de esquizofrênicos e controles. Estas foram tratadas com TBHQ, um pró-oxidante, ou DMSO, o veículo, e então se quantificou a expressão dos genes MMP16, GALNT6, SULF1, ADAMTS1 e ACSL1pelo método de PCR em tempo real e dos seus produtos por western blot. Resultados: existe resposta de ambos os grupos ao estresse oxidativo, no entanto, essa resposta é distinta entre pacientes e controles, com esquizofrênicos expressando menos o gene GALNT6 e sua proteína. Conclusão: o gene GALNT6 codifica uma enzima responsável por glicosilar componentes da MEC. Pode-se hipotetizar que a resposta de esquizofrê-nicos ao estresse oxidativo torna essa MEC mais suscetível aos seus efeitos deletérios, colaborando com a fisiopatologia da doença.

Introduction: The pathophysiology of schizophrenia is still poorly understood. Several studies suggest an important role of inflammation and oxidative stress in this explanation. Schizophrenics seem to have altered defense mechanisms and a distinct response to oxidative stress than that of controls. Oxidative stress is harmful to various cellular structures,among them the extracellular matrix (ECM). A intact and structured ECM is essential for proper synaptic signaling. Objective: To evaluate the response of genes encoding ECM proteins to oxidative stress in chronic schizophrenics and controls. Methodology: Fibroblasts were cultivated from schizophrenic and controls? skin biopsies. They were treatedwith TBHQ, a pro-oxidant, or DMSO (the vehicle), and then had the expression of MMP16, GALNT6, SULF1, ADAMTS1 and ACSL1 genes quantified by the method of real time PCR and their products by the method of Western blot. Results: There was response from both groups to oxidative stress, however, this response was different between patients and controls, with schizophrenics expressing less the GALNT6 gene and its protein. Conclusion: GALNT6 gene encodes an enzyme responsible for glycosylating ECM components. We can hypothesize that the schizophrenic?s response to oxidative stress renders the ECM moresusceptible to its harmful effects, contributing to the pathophysiology of the disease.

Propriedades psicométricas de um protocolo neuropsicológico breve para uso em populações geriátricas / Psychometric properties of a brief neuropsychological protocol for use in geriatric populations

CONTEXTO: O aumento na expectativa de vida e na proporção de idosos na população tem acarretado elevação nas taxas de prevalência de demências. O diagnóstico correto da demência é muito importante para o tratamento clínico e para um melhor prognóstico. Por isso, é necessário adaptar e desenvolver instrumentos para o diagnóstico diferencial entre os processos de envelhecimento normal e patológico. OBJETIVO: Avaliar as propriedades psicrométricas e a estrutura fatorial de um protocolo neuropsicológico usado para avaliação geriátrica. MÉTODO: Pacientes (n = 69) com queixas cognitivas heterogêneas foram avaliados no Núcleo de Geriatria e Gerontologia do Hospital das Clínicas da Universidade Federal de Minas Gerais, a partir de um protocolo composto pelo Miniexame do Estado Mental, Desenho do Relógio, Cubos de Corsi, Fluência Verbal, Span de Dígitos e Token Test. A análise estatística incluiu análise fatorial dos resultados dos testes, correlação de Pearson entre o fator obtido e a idade, escolaridade, anos de educação formal e a Classificação Clínica das Demências (CDR) e a área sob a curva ROC. RESULTADOS: A análise fatorial dos escores do teste mostrou um fator geral representativo que teve associação moderada e significativa com o CDR (r = -0,672; p < 0,001) e anos de educação formal (r = 0,455; p < 0,001). Esse fator teve fraca, mas significativa, correlação com a idade (r = -0,282; p < 0,05). CONCLUSÃO: Esses resultados apontam para uma boa validade de construto e de critério do protocolo na avaliação do declínio cognitivo de idosos. Estudos futuros sobre aplicabilidade e normas populacionais são necessários para aprimorar o uso clínico desse protocolo de avaliação.

BACKGROUND: The increase in life expectancy and proportion of elderly in the population is causing an increase in dementia prevalence rates. The correct, early dia gnosis of dementia is very important to clinical treatment and to improved prognosis. Therefore, it is necessary to adapt and develop assessment tools for the differential diagnosis between pathological and normal aging processes. OBJECTIVE: Assess the psychometric properties and the factorial structure of a neuropsychological protocol used in geriatric assessment. METHOD: Subjects (n = 69) with heterogeneous cognitive complaints were assessed at the Geriatric and Gerontologic Clinic at the Clinical Hospital of the Federal University of Minas Gerais using a protocol composed of the Mini-Mental State Examination, Clock Drawing, Corsi Blocks, Verbal Fluency, Digit Span and Token Test. Statistical analyses included factorial analyses of test results, Pearson's correlation between obtained factor, age, years of formal education and Clinical Dementia Rating (CDR) and area under the ROC curve. RESULTS: The factorial analyses of test scores showed a general representative factor that had moderate and significant association with CDR (r = -0.672; p < 0.001) and years of formal education (r = 0.455; p < 0.001), respectively. This factor had weaker and less significant correlation with age (r = -0.282; p < 0.05). DISCUSSION: These results point to the protocol's good construct and criteria validity in assessing cognitive decline in the elderly. Future works concerning applicability and populational norms are needed to improve the clinical use of this assessment protocol.