Adverse Drug Reactions during COVID-19 Treatment: A Comprehensive Analysis Focused on Hospitalized Patients, with the Use of a Survey in Cuba in 2020.

Aims: To evaluate the prevalence and type of adverse drug reactions (ADRs), together with associated risk factors, among Cuban COVID-19 patients treated with chloroquine (CQ), lopinavir/ritonavir (LPV/r), or interferon α2b (IFN α2b), according to the Cuban protocol. Materials and Methods: A prospective descriptive analysis of ADRs was performed on 200 COVID-19 patients who were admitted consecutively to three hospitals in Havana and Pinar del Río from April to July 2020. Information on demographics, ADRs, outcomes, behavioral, and health-related factors was collected using a validated questionnaire and clinical records. Each potential ADR case was assessed for causality based on the WHO-UMC algorithm, concomitant drug influences, and the presence of any drug-drug interactions (DDI). Results: The total frequency of ADRs was 55%, with predominantly gastrointestinal disorders and general symptoms (23% vs 20%). 95.1% of ADRs occurred within 10 days after treatment and 42 potential DDI in 55.5% of patients (61/110) were observed. The prevalence of ADRs was: 44%, 30.4%, and 26.4% for IFN α2b, LPV/r, and CQ, respectively. Sex (odds ratio (OR): 0.40 (95% confidence interval (CI): 0.211-0.742), age (OR: 2.36 (95% CI: 1.02-5.44)), and underlying diseases (OR: 0.12 (95% CI: 0.06-0.23)) were independently associated factors for ADRs (P < 0.05). Conclusions: The frequency of ADRs and potential DDI was high compared to their use during nonpandemic times (e.g., for malaria, HIV, or inflammatory diseases). The safety profile of these drugs when used for COVID-19 treatment showed similar characteristics. Comorbidities, age >37 years old, and female sex were associated with ADRs.

El distrés oxidativo y sus implicaciones moleculares en algunas enfermedades infecciosas: una revisión / Oxidative distress and its molecular implication for some infectious diseases: A review

Introducción: Las especies reactivas de oxígeno, nitrógeno y azufre (ERONS) se generan continuamente en la fisiología de los organismos. Como parte de la respuesta de las células inmunitarias frente a los patógenos podrían aumentar y producir distrés oxidativo, citotoxicidad y daño de los órganos. El reconocimiento de las implicaciones moleculares de las ERONS todavía es un campo de investigación en desarrollo. Objetivo: Describir los aspectos moleculares relacionados con el metabolismo oxidativo y algunos patógenos (virus, parásitos, bacterias y hongos) en relación con las infecciones. Métodos: Se identificaron 520 documentos relacionados con los criterios de búsqueda en las bases de datos LILACS, Science Direct, SciELO, EMBASE, PubMed e Infomed, con los buscadores Google y Google académico. De estos, fueron analizados 78 documentos publicados a partir de 1980 al 2021 en español o inglés y organizados en 7 subtemas. Información, análisis y síntesis: Los agentes infecciosos y el hospedero interactúan produciendo ERONS que pueden superar los sistemas de defensa antioxidantes e influyen en el distrés oxidativo. Los procesos biológicos asociados al estado redox se relacionan con los factores de transcripción Nrf2 y NF-κB. Ambos permiten una respuesta celular entre la susceptibilidad y la resistencia a los agentes infecciosos, por lo que pueden iniciar o acelerar procesos fisiopatológicos en el organismo. En general la respuesta redox en la fisiopatología infecciosa está interconectada con la reprogramación metabólica, las respuestas antimicrobianas e inflamatorias y la disfunción celular o de tejido. Conclusiones: Los eventos moleculares redox pueden participar en diversas enfermedades infecciosas, mediando diferentes respuestas o trastornos asociados.

Introduction: Reactive oxygen/nitrogen/sulfur species (RONSS) are continuously generated in the physiology of organisms. As part of the immune cell response to pathogens, they may increase and lead to oxidative stress, cytotoxicity and organ damage. Recognizing the molecular implications of RONSS is still a developing field of research. Objective: To describe the molecular aspects related to oxidative metabolism and some pathogens (viruses, parasites, bacteria and fungi) in relation to infections. Methods: Based on the search criteria, 520 documents were identified in LILACS, Science Direct, SciELO, EMBASE, PubMed and Infomed databases, using the search engines Google and Google Scholar. Of these, 78 documents published from 1980 to 2021 in Spanish or English and organized into seven subtopics were analyzed. Information, analysis and synthesis: Infectious agents and the host interact to produce RONSS that can overcome antioxidant defense systems influencing on oxidative stress. Biological processes associated with the redox state are related to the transcription factors Nrf2 and NF-κB. Both generate a cellular response between susceptibility and resistance to infectious agents, thus they can initiate or accelerate pathophysiological processes in the organism. In general, the redox response in infectious pathophysiology is interconnected with metabolic reprogramming, antimicrobial and inflammatory responses, and cellular or tissue dysfunction. Conclusions: Molecular redox events may be involved in various infectious diseases, where different associated responses or disorders mediate.

Oxidative stress in hepatitis C virus-human immunodeficiency virus co-infected patients.

INTRODUCTION AND OBJECTIVES: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) co-infection generates sustained inflammation with increased reactive oxygen species production. The pathogenic impact of systemic oxidative stress is known to influence drug treatment and follow-up. The aim of this case-control study was to compare the redox status in HCV-HIV co-infected with respect to HIV-infected individuals and to explore the relation between redox and HIV follow-up variables. PATIENTS OR MATERIALS AND METHODS: Blood samples were drawn from 330 individuals divided into three groups: HIV, HCV-HIV and presumable healthy subjects. Redox, hematological, hemochemical, immunologic and virological indexes were determined. RESULTS: Both HIV groups had significant differences in global indexes of damage and antioxidant status (p<0.05) with respect to the supposedly healthy individual group. HCV-HIV group showed a significantly higher damage (total hydroperoxide and advanced oxidation protein products) compared to the control and HIV groups (p<0.05). The overall modification of the redox indexes showed that 72% of individuals with simultaneous detrimental differences were related to HCV-HIV condition. CONCLUSIONS: These results corroborate that oxidative stress occurs in the HIV condition and also during HCV-HIV co-infection, with different molecular changes of follow-up indexes. Redox indexes diagnosis should be considered in early diagnosis and treatment of HCV-HIV co-infection.

Pharmacogenetic Markers: A Path toward Individualized HIV Therapy.

INTRODUCTION Approximately 73% of persons with HIV who receive antiretroviral therapy in Cuba are in viral suppression. The non-response of the remaining 27% could be due to several factors including adverse drug reactions and HIV resistance to antiretroviral drugs, as well as social factors and idiosyncratic characteristics of each patient. Genetic information explains from 20% to 95% of a drug's effects and variations in response. Considering optimization of therapeutic efficacy in our country, genetic factors of the host should be identified. OBJECTIVE Identify polymorphisms affecting genetic variability of responses to antiretroviral drugs. EVIDENCE ACQUISITION A literature review was conducted (of original articles, published theses, clinical reports and bibliographic review studies, from 2000 to 2018, in Spanish and English listed in MEDLINE/PubMed, SciELO, LILACS, PharmGKB and Google Scholar) with the following key words: pharmacogenetics, human immunodeficiency virus, anti-retroviral agents, genetic polymorphism, genetic techniques, pharmacogenomic variants. DEVELOPMENT The review identified 77 relevant publications meeting specific quality criteria. A summary table was built with data collected on antiretroviral drugs, genes and proteins involved in polymorphic variations, their associated effects and relevant scientific references. Information was included on polymorphisms related to 12 antiretroviral drugs used in HIV therapy. Polymorphisms determine variations in proteins involved in drug transport and metabolism and in elements of immunity. Relevant pharmacogenetic biomarkers recognized by drug regulatory agencies were identified. CONCLUSIONS The study identified genetic variations (single-nucleotide polymorphisms) associated with 12 antiretroviral drugs. In most cases, no statistically significant causal association was found. Identifying polymorphic variations is a medium- and long-term objective that requires statistical support and adoption of strategies to optimize antiretroviral therapy. An approach combining plasma-level monitoring and pharmacogenetic analysis is recommended to optimize therapy for HIV patients. KEYWORDS Pharmacogenetics, HIV, anti-retroviral agents, antiretroviral therapy, genetic polymorphism, genetic techniques, pharmacogenomic variants.

La Farmacovigilancia en Cuba y la Infranotificaciones de Reacciones Adversas a los Medicamentos / Pharmacovigilance in Cuba and Adverse Reactions to Drugs Underreporting / Farmacovigilância em Cuba e Subnotificações de Reções Adversas a Medicamentos / Pharmacovigilance à Cuba et Sous-déclaration des Réactions Indésirables aux Médicaments

Resumen Objetivo: Efectuar una revisión de los conocimientos sobre la Farmacovigilancia, el suministro de información sobre sospechas de RAM, que es tanto un deber moral para el médico y otros profesionales de salud como un aspecto de la atención al paciente y la infranotificación de estos reportes. Material y métodos: La revisión fue realizada en las bases de datos LILACS, PAHO, SciELO, EMBASE, PubMed e Infomed, los motores de búsqueda Google y Google Scholar donde se colocaron palabras claves para la búsqueda de la información en artículos originales, tesis, otros artículos de revisión bibliográfica y revistas de elevado índice de citación publicados desde 1937 a 2017, en los idiomas español o inglés. Resultados: Se identificaron 100 artículos, de los cuales 30 fueron seleccionados como útiles verificados para actualizar los conceptos relacionados con las disciplinas de Farmacovigilancia. En la práctica clínica existen varios factores que pueden dificultar la detección de las RAM y como consecuencia contribuir a la infranotificación. Conclusiones: La infranotificación en Farmacovigilancia es una realidad mundial, observándose que la mayoría de las publicaciones analizadas que proceden de Europa (Alemania, España y Reino Unido) y en países de América Latina como Colombia, reconocen bajos índices de notificación.

Abstract Object: The article proposes a pharmacovigilance knowledge review, the provisión of information on suspicion of AMR, which is both a moral duty for the doctor and other health professionals and an aspect of patient care and the underreporting of them. Materials and methods: The review was carried out in the databases LILACS, PAHO, SciELO, EMBASE, PubMed and Infomed, the Google search engines and Google Scholar where keywords were placed for the search of the information in original articles, theses, other articles of bibliographic review and high citation index journals published from 1937 to 2017, in Spanish or English. Results: Consequently 100 articles were identified, 30 of which were selected as verified tools to update the concepts related to Pharmacovigilance discipline. There are several factors in clinical practice that can hinder the detection of ADR and it could contribute to under-reporting. Conclusión: In pharmacovigilance the under-reporting is a global reality, noting that most of the analyzed publications come from Europe (Germany, Spain and the United Kingdom) and in Latin American countries such as Colombia, recognize low reporting rates.

Resumo Objetivo: O artigo propõe uma revisao de literatura sobre farmacovigilancia, fornecendo informações sobre suspeitas de RAM, que é um dever moral para os médicos e outros profissionais de saúde como um aspecto da assistencia ao doente e subnotificação desses relatórios. Materiais e métodos: A pesquisa foi realizada nas bases de dados LILACS, PAHO, SciELO, EMBASE, PubMed e Infomed, nos motores de busca Google e Google Scholar, onde foram colocadas as palavras-chave para encontrar as informações em artigos originais, teses, outros artigos de revisão bibliográfica e de revistas de alto índice de citação publicados de 1937 a 2017, em espanhol ou inglês. Resultados: Foram identificados 100 artigos, dos quais 30 foram selecionados como instrumentos importantes para atualização dos conceitos relacionados á disciplina de farmacovigilancia. Na prática clínica, existem vários fatores que podem dificultar a detecção de RAM e, consequentemente, contribuir para uma subnotificação Conclusão: Na farmacovigilãncia, a subnotificação é uma realidade mundial, observando que a maioria das publicações analisadas provenientes da Europa (Alemanha, Espanha e Reino Unido) e dos países latino-americanos como a Colõmbia, reconhecem baixos índices de notificação.

Résumé Objectif: Procéder á une revue de littérature des connaissances sur la pharmacovigilance et la fourniture d'informations sur la suspicion de Réactions Indésirables aux Médicaments (RIM), qui est autant un devoir moral pour le médecin et pour d'autres professionnels de la santé qu'un aspect des soins aux patients, ainsi que sur la sous-déclaration. Matériaux et méthodes: La revue a été réalisée á l'aide des bases de données LILACS, PAHO, SciELO, EMBASE, PubMed et INFOMED, et des moteurs de recherche Google et Google Scholar, en utilisant des mots clés pour chercher des informations dans des articles originaux, théses, articles de revue de littérature et revues ayant des indices de citations élevés, publiés entre 1937 et 2017, en espagnol ou en anglais. Résultats: 100 articles ont été identifiés, dont 30 ont été sélectionnés comme utiles pour actualiser les concepts en relation avec les disciplines impliquées dans la pharmacovigilance. Dans la pratique clinique, plusieurs facteurs peuvent entraver la détection des RIM et, par conséquent, contribuer á la sous-déclaration. Conclusions: La sous-déclaration en pharmacovigilance est une réalité mondiale. Dans la plupart des publications analysées provenant d'Europe (Allemagne, Espagne et Royaume-Uni) et des pays d'Amérique latine comme la Colombie, on a pu observer la reconnaissance d'un faible taux de déclaration.

Cuban Strategy and Medical Cooperation to Combat Ebola, 2014-2016.

The Ebola virus is a pathogen that causes high morbidity and mortality in epidemic events during which health personnel are frequently infected. Such an epidemic occurred in West Africa, prompting WHO to issue a call in 2014 for health personnel to be dispatched to affected countries. Cuba responded and signed an assistance agreement under which 265 Cuban health professionals, members of the Henry Reeve Emergency Medical Contingent, volunteered their services in the Republic of Guinea, Sierra Leone and Liberia. This article presents Cuba's strategy of medical aid and organization of the three medical teams formed; refers to the teams' contribution to epidemic control in treatment centers where they worked alongside other personnel; and describes measures taken in Cuba to prevent the virus from entering the country through returning volunteers or other means. In the centers where Cuban medical teams worked with other health professionals in West Africa, case fatality decreased from 80%-90% to 24%, contributing to control of the epidemic; no Ebola outbreaks occurred in Cuba. During the epidemic, two Cuban health professionals died of malaria and one physician fell ill with Ebola. This paper includes an overview of the treatment and evolution of the latter case, a doctor who contracted the disease in Sierra Leone and was treated in Geneva and Havana. KEYWORDS Ebola virus, treatment, strategy, followup, medical collaboration, Republic of Guinea, Sierra Leone, Liberia, Cuba.

Antioxidantes con productos bioactivos naturales de origen vegetal o sintéticos como complemento de la terapia en la infección VIH/sida / Antioxidants with natural bioactives of vegetable or synthetic origin´s products as complement of the therapy in the HIV/aids infection

Introducción: El estrés oxidativo es considerado un cofactor en la patogénesis del virus de inmunodeficiencia humana. La influencia de este tipo de estrés en la progresión de la enfermedad ha afectado a pacientes tratados con terapia antirretroviral de alta eficacia. Según evidencias moleculares, esa terapia no reduce los niveles de daño oxidativo. Objetivo: Compilar información sobre las principales implicaciones fisiopatológicas del metabolismo oxidativo asociadas a la infección VIH/sida y a la terapia antirretroviral, y las evidencias más actuales sobre las alternativas de suplementación antioxidante con productos sintéticos o bioactivos naturales de origen vegetal aplicadas en los pacientes infectados con ese virus. Métodos: Se consultaron las bases de datos Medline, PubMed, SciELO, LILIACS y los motores de búsqueda Google y Google Scholar. Se descartaron las publicaciones que no se ajustaban al tema, tenían insuficientes datos de origen o las que eran propaganda no científica. Se analizaron 74 artículos publicados desde 1990 hasta 2017. Resultados: La deficiencia de la ingesta de micronutrientes antioxidantes exacerba el estrés oxidativo en los infectados por ese virus. Las combinaciones de suplementos antioxidantes evaluadas en estudios clínicos a nivel internacional son diversas y sus resultados han sido controversiales Si se consideran los elementos previos, la suplementación antioxidante podría resultar beneficiosa, pues influye en las comorbilidades asociadas al progreso de esta infección y su tratamiento. Conclusión: El uso de antioxidantes podría ser una alternativa para complementar el tratamiento del VIH dirigido a restaurar las funciones inmunes y minimizar los efectos tóxicos secundarios relacionados con los antirretrovirales y la oxidación durante el contagio.

Introduction: Oxidative stress is considered a cofactor in human immunodeficiency virus pathogenesis. In populations of human immunodeficiency virus infected patients treated with highly active antiretroviral therapy, the role of oxidative stress in disease progression has become more complicated. According to molecular evidences, the therapy does not reduce the levels of oxidative damage. The deficiency of antioxidant micro-nutrient consumption increases the oxidative stress in the patients infected with the virus. Objective: The article propose a compilation of evidences on the main physiopathological implications of oxidative metabolism associated to the HIV/AIDS infection and the antiretroviral therapy, and the most updated evidences on the alternatives of antioxidant supplementation with synthetic or natural bioactive of vegetal origin's products applied in the patients infected with the virus. Methods: The databases Medline, PubMed, SciELO, LILIACS and the search motors Google and Google Scholar were consulted. Were discarded the publications that were not adjusted to the topic, had insufficient origin data or those that were nonscientific propaganda. Seventy four articles from 1990 to 2017 were consulted including bibliographic revisions, originals and books. Results: In human immunodeficiency virus infected individuals deficient antioxidant micronutrients intake exacerbates oxidative stress. Antioxidant supplementation may be beneficial in minimizing the co-morbidities associated with this infection, its progression and treatment. Conclusion: The option for its use could be an alternative that complement human immunodeficiency virus treatment to restore immune functions and minimizing toxic side effects related to highly active antiretroviral therapy or oxidation during infection.

Abacavir: una revisión actualizada sobre sus propiedades y aplicaciones / Abacavir: an updated review on its properties and applications

El Plan Estratégico Nacional para la Prevención y Control de las ITS/VIH/sida, 2014-2018 en Cuba establece un grupo de acciones entre las que se encuentra la estandarización y optimización de esquemas de terapia antirretroviral, adecuación del inicio del tratamiento a las recientes recomendaciones de la Organización Mundial de la Salud, mejorar la calidad de la atención, la adherencia y la reducción del costo de los medicamentos. Para cumplir estas tareas se prevé introducir en el Cuadro Básico de Medicamentos algunos antirretrovirales genéricos cubanos para incrementar las posibles combinaciones de Terapia Antirretroviral de Alta Eficacia a disposición de los pacientes que viven con el virus de la inmunodeficiencia humana y sustituir importaciones. Se realizó una revisión bibliográfica exhaustiva para la actualización de la comunidad médica y científica; se examinaron las principales características del abacavir: propiedades químico-físicas del principio activo, sus presentaciones comerciales, mecanismo de acción, farmacocinética y resistencia, reacciones adversas e interacciones, aplicaciones terapéuticas, dosificaciones, ajustes de dosis y seguridad en el embarazo. Para ello se consultaron un total de 58 artículos que incluyeron revisiones bibliográficas, trabajos originales, fichas técnicas, libros, conferencias y reportes. El abacavir es un antirretroviral relativamente nuevo y ampliamente recomendado por las guías de tratamiento por su efectividad demostrada(AU)

The National Strategic Plan for the Prevention and Control of the IST/HIV/ aids, 2014-2018 in Cuba establishes a group of actions such as the standardization and optimization of antiretroviral therapy schedules, adaptation of the beginning of the treatment to the recent recommendations of the World Health Organization, the improvement of the quality of care, the adherence to and the reduction of the cost of medications. For the purpose of complying with these tasks, it is anticipated to introduce in the basic drug listing some Cuban generic antiretroviral drugs to increase the possible combinations of the Highly Active Antiretroviral Therapy available for patients who live with the human immunodeficiency virus and to reduce imports. An exhaustive literature review was made for the update of the medical and scientific community knowledge. This article analyzed the main characteristics of abacavir such as chemical-physical properties of the active principle, their commercial presentations, mechanism of action, pharmacokinetics and resistance, adverse reactions and interactions, therapeutic applications, dosages, dose adjustments and safety at pregnancy. To this end, a total of 58 articles were consulted including literature reviews, original papers, technical records, books, lectures and reports. Abacavir is a relatively new antiretroviral, widely recommended by treatment guidelines on account of its proven effectiveness(AU)

Estado redox en pacientes infectados por VIH/sida con insuficiencia renal crónica sometidos a hemodiálisis / The redox state of VIH/AIDS patients suffering chronic renal failure and undergoing hemodyalisis

Introducción: el balance redox alterado en el curso de la insuficiencia renal crónica ha sido considerado un factor contribuyente a la morbilidad y mortalidad de la enfermedad y un factor asociado a la progresión de la infección por sida.Objetivo: valorar el estado redox en pacientes infectados por VIH con insuficiencia renal crónica que requirieron hemodiálisis.Métodos: se realizó un estudio de casos y controles en 20 pacientes VIH/sida con insuficiencia renal crónica y 40 individuos aparentemente sanos. Se realizaron determinaciones de malonildialdehído, glutatión, superóxido dismutasa, catalasa, productos avanzados de la oxidación de proteínas, hidroperóxidos y potencial de peroxidación, conjuntamente con los marcadores de progresión: conteo de linfocitos T CD4+ y carga viral y una serie de determinaciones hemoquímicas y hematológicas. El análisis se realizó antes, a los 30 min y a los 240 min del tratamiento dialítico. Estadísticamente se verificaron los supuestos de igualdad de varianza y normalidad de las variables, y en dependencia se aplicó una prueba paramétrica o no paramétrica. El resultado fue significativo para p< 0,05.Resultados: los indicadores del estado redox se encontraron alterados en los pacientes estudiados con respecto al grupo supuestamente sano antes de la hemodiálisis. Se mostró un valor mayor significativo (p< 0,05) de los índices malonildialdehído, productos avanzados de la oxidación de proteínas, superóxido dismutasa, y un valor menor de catalasa y glutatión a los 240 min de realizada la diálisis, con la excepción de los hidroperóxidos que no mostraron cambios. La carga viral plasmática disminuyó de manera significativa en el proceso.Conclusiones: los resultados sugieren que el proceso dialítico en este tipo de pacientes favorece el estrés oxidativo, conjuntamente con una disminución de la carga viral plasmática. El estudio aporta valor metodológico en el manejo de estos pacientes y en la búsqueda por mejorar su calidad de vida

Indicadores del estrés oxidativo en pacientes afectados por VIH/sida con manifestaciones reumatológicas / Oxidative stress indicators for HIV/AIDS patients with rheumatologic manifestations

Introducción: el estrés oxidativo se ha reconocido como cofactor en la progresión de la infección por el virus de la inmunodeficiencia humana (VIH) y en las manifestaciones reumatológicas. Objetivo: valorar los indicadores del estrés oxidativo en los pacientes afectados por VIH con manifestaciones reumatológicas. Métodos: se estudiaron 31 pacientes VIH con manifestaciones reumatológicas y se compararon los índices evaluados con un grupo control, 31 individuos aparentemente sanos. Los pacientes fueron clasificados según los siguientes criterios de actividad: escala de actividad de la enfermedad para manifestaciones reumatológicas, e índice de actividad de enfermedad y la escala visual analógica de dolor nocturno para manifestaciones reumatológicas. Las concentraciones plasmáticas de los indicadores de estrés oxidativo fueron cuantificadas mediante técnicas espectrofotométricas y el análisis estadístico realizado, mediante el programa estadístico SPSS 13. Resultados: los pacientes VIH evaluados presentaron un estrés oxidativo de moderado a severo, caracterizado por aumento significativo de los parámetros indicadores de daño oxidativo y disminución de los sistemas antioxidantes (p< 0,05), con respecto a lo evaluado en un grupo de pacientes supuestamente sanos relacionado en edad y género. No se encontró significación estadística en los estudios de asociación de las manifestaciones reumatológicas, el tiempo transcurrido desde el diagnóstico confirmado de la infección por el VIH y género, conteo de linfocitos T CD4+ ni la carga viral. Conclusiones: los datos muestran que los indicadores del proceso de estrés oxidativo empleados en los pacientes afectados por VIH con manifestaciones reumatológicas, podrían ser útiles en su seguimiento y tratamiento

Introduction: the oxidative stress has been recognized as a cofactor in the progression of the human immunodeficiency virus (HIV) infection and in the rheumatologic manifestations. Objective: to assess the oxidative stress indicators in those HIV patients with rheumatologic manifestations. Methods: thirty one HIV patients with rheumatologic manifestations were studied and the evaluated indexes were compared to those of a control group made up of 31 apparently healthy individuals. The patients were classified according to the following activity criteria: scale of the disease activity for the rheumatologic manifestations, and index of disease activity and the analogical visual scale of pain at night in terms of the rheumatologic manifestations. The plasma concentrations of the oxidative stress indexes were measured by spectrophotometric techniques. Statistical analysis was made using SPSS 13 program. Results: the evaluated HIV patients presented with moderate to severe oxidative stress, characterized by significant increase in the oxidative damage parameters and decrease in the antioxidizing systems (p< 0.05) after a comparison with those parameters of an apparently healthy control group in terms of age and gender. No statistically significance was found in the studies carried out to relate rheumatologic manifestations, time elapsed from the HIV confirmation, gender, CD4 lymphocyte T count and the viral load. Conclusions: the collected data showed that the oxidative stress indicators could be useful in treating and following-up the HIV patients with rheumatologic manifestations

Oxidative stress as a cofactor in spinocerebellar ataxia type 2.

Spinocerebellar ataxia type 2 (SCA2) is a redox-sensitive neurodegenerative disease affecting the cerebellum, fibre connections in the cerebellum, the peripheral nervous system, and extracerebellar central pathways. Currently, Cuba has the highest reported global rate for this disease. The aim of this review article is to summarize and discuss the current knowledge about evidence of oxidative stress during SCA2. Recent reports have suggested that ataxin 2 and other related factors contribute to the redox imbalance in this disease. It is important to recognize and clarify the molecular mechanisms associated with the redox imbalance to consider ataxias innovative approaches to counteract oxidative stress-induced tissue damage, through alternative therapeutic or nutritional intervention in SCA2 and related diseases.

Systems biology of antioxidants.

Understanding the role of oxidative injury will allow for therapy with agents that scavenge ROS (reactive oxygen species) and antioxidants in the management of several diseases related to free radical damage. The majority of free radicals are generated by mitochondria as a consequence of the mitochondrial cycle, whereas free radical accumulation is limited by the action of a variety of antioxidant processes that reside in every cell. In the present review, we provide an overview of the mitochondrial generation of ROS and discuss the role of ROS in the regulation of endothelial and adipocyte function. Moreover, we also discuss recent findings on the role of ROS in sepsis, cerebral ataxia and stroke. These results provide avenues for the therapeutic potential of antioxidants in a variety of diseases.

Efecto del Vimang® en pacientes VIH/sida / Effect of Vimang® in HIV/AIDS patients

ANTECEDENTES: el estrés oxidativo ha sido considerado como cofactor de la progresión de la infección por el VIH al estado sida. OBJETIVOS: evaluación del posible efecto antioxidante y de las funciones de diversos sistemas en el organismo, que resultan en la seguridad toxicológica para su empleo. MÉTODOS: considerando lo anterior se estudiaron 68 individuos seropositivos al VIH de modo aleatorio, a doble ciegas en dos grupos: a uno se le suministró Vimang® durante 6 meses y al otro placebo. Se hicieron determinaciones del estado redox, índices bioquímicos de función renal, hepática y hematológica, y se realizó una evaluación de la ingesta dietaria a través de encuestas durante 7 d al inicio y al final del estudio. RESULTADOS: se evidenció de manera estadísticamente significativa (p< 0,05), un cambio beneficioso en los índices redox en el grupo con Vimang® respecto al placebo. No se encontraron diferencias significativas en la comparación de los índices dietarios evaluados, ni en los índices bioquímicos de función renal, hepática y hematológica entre los grupos, ni al final del estudio. CONCLUSIONES: las evidencias demuestran el efecto antioxidante del Vimang® sin influencias tóxicas en el período de 6 meses en los individuos VIH/sida estudiados.

INTRODUCTION: the oxidative stress (OS) has been recognized as a co-factor of HIV infection evolution to AIDS condition. OBJECTIVES: to evaluate the possible antioxidant effect and the impact on the functioning of several systems in the body, resulting in the toxicological safety of Vimang® use. METHODS: sixty eight HIV-seropositive patients were double-blind randomized in two groups; the first was supplied with Vimang® during six months and the other with placebo. Redox condition and the biochemical indexes of the hematological, renal and hepatic functions were measured. Also, dietary intake was assessed through surveys administered for 7 days at the beginning and at the end of the study. RESULTS: there were statistically significant differences between the groups regarding positive change in redox figures in Vimang® group compared to those of the placebo group. No significant difference was found either in the evaluated dietary intake indexes or in the biochemical indexes of the renal, hematological and hepatic functions at the end of the study. CONCLUSIONS: Vimang® antioxidant effect was shown, without any toxic influence during the six month-study conducted in HIV/AIDS patients.

WITHDRAWN: Modification in redox status of diabetes mellitus type 1 patients after insulin transition.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.bionut.2010.09.005. The duplicate article has therefore been withdrawn.

WITHDRAWN: Oxidative stress in aging: Theoretical outcomes and clinical evidences in humans.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.biomag.2011.03.001. The duplicate article has therefore been withdrawn.

[Effect of Vimang in HIV/AIDS patients]. / Efecto del Vimang en pacientes VIH/sida.

INTRODUCTION: the oxidative stress (OS) has been recognized as a co-factor of HIV infection evolution to AIDS condition. OBJECTIVES: to evaluate the possible antioxidant effect and the impact on the functioning of several systems in the body, resulting in the toxicological safety of Vimang use. METHODS: sixty eight HIV-seropositive patients were double-blind randomized in two groups; the first was supplied with Vimang during six months and the other with placebo. Redox condition and the biochemical indexes of the hematological, renal and hepatic functions were measured. Also, dietary intake was assessed through surveys administered for 7 days at the beginning and at the end of the study. RESULTS: there were statistically significant differences between the groups regarding positive change in redox figures in Vimang group compared to those of the placebo group. No significant difference was found either in the evaluated dietary intake indexes or in the biochemical indexes of the renal, hematological and hepatic functions at the end of the study. CONCLUSIONS: Vimang antioxidant effect was shown, without any toxic influence during the six month-study conducted in HIV/AIDS patients.

Estudio de bioequivalencia: formulaciones genéricas y comerciales de estaduvine, lamiduvine, zidovudine e indinavir en pacientes cubanos infectados con VIH / Bioequivalence study: generic and trade formulations of stavudine, lamivudine, zidovudine and indinavir in Cuban HIV-infected subjects

Objetivo: El presente estudio describe los estudios de bioequivalencia de los genéricos cubanos antirretrovirales estavudina, lamivudina, zidovudina e indinavir con respecto a sus productos innovadores. Diseño: Los estudios de bioequivalencia de cada antirretroviral estudiado (formulación de prueba, P y referencia, R), se realizaron en 13 ó 14 sujetos, según el caso con la utilización de las medias en un estudio aleatorio, cruzado y a dosis única con un período de lavado de 10 días. Métodos: Las concentración de los antirretrovirales en plasma se monitorearon durante un período de 12 h después de la administración de estos, mediante el uso de métodos validados de cromatografía líquida de alta resolución (HPLC). Los parámetros farmacocinéticos se determinaron con el uso el software profesional WinNolin, versión 2.1. La comparación de los parámetros farmacocinéticos se realizó con un intervalo de confianza del 95 por ciento con la utilización del software NCSS 2000 PASS 2000 (hipótesis nula). Para el estudio de bioequivalencia se usó el software Equiv Test de soluciones estadísticas, empleando ANOVA con el 90 por ciento de intervalo de confianza. Resultados: El presente estudio mostró que no se observaron diferencias significativas en las medias de AUC0-12, AUC0-¥, Cmax y Tmax de ambas formulaciones de estavudina, lamivudina, zidovudina e indinavir. Se concluye que los parámetros farmacocinéticos estudiados se encuentran dentro de los rangos establecidos siendo 80-125 por ciento para Cmax, AUC0-12, y AUC0-¥. En el caso de Cmax de la zidovudina el rango fue 70-143 por ciento. Conclusión: Estos resultados avalan que los genéricos antirretrovirales cubanos son bioequivalentes con sus respectivos productos innovadores en términos de velocidad y magnitud de la absorción

Altered redox status in patients with diabetes mellitus type I.

Diabetes mellitus is a complex metabolic disorder characterized by a disturbance in glucose metabolism. Recent evidences suggest that increased oxidative damage as well as deficits in antioxidants defence systems could be related to the complications in Diabetes patients' type I. The aim of this study was to investigate an extensive array of redox status indices: glutathione (GSH), malondialdehyde (MDA), peroxidation potential, superoxide dismutase (SOD), catalase (CAT), total hydroperoxide (TH) and advanced oxidation protein products (AOPP) in relation to blood glucose and glucose indicators control such as glycosylated haemoglobin (HbA1c) and fructosamine by spectophotometric techniques. Forty Diabetes Mellitus patients' type I and 40 healthy subjects were recruited. Both a reduction of GSH levels and an increase in MDA and TH levels were observed in the serum of patients. These patients also showed an increase of AOPP and PP levels as well as an increase of both CAT and SOD activity. Relatively to the control group, patients had significant differences in global indices of oxidant/antioxidant status and indicators of glycaemia control. These results contribute both to the evidences that substantial oxidative stress occurs during Diabetes Mellitus type I without early complications and to an integral overview of the oxidant/antioxidant balance in these patients.

Efectos del VIMANG sobre algunos marcadores de progresión de la infección por VIH-1 en pacientes cubanos / Effects of VIMANG on some markers of HIV-1 progression in Cuban patients

Se estudiaron 68 pacientes divididos en 2 grupos, uno que recibió VIMANG durante 6 meses y otro que recibió placebo. Se midieron títulos de anticuerpos anti-p24 y concentración de antígeno p24 al tiempo 0 y 6 meses. Las diferencias encontradas en el comportamiento de los títulos de anticuerpos entre ambos grupos no resultaron ser significativas, aunque se mantuvieron los TPG en el grupo que recibió VIMANG. En el grupo placebo, 2 pacientes elevaron la concentración de antígeno y 2 se mantuvieron positivos para este marcador, mientras que en el grupo estudio desapareció el antígeno en un paciente, que se tornó positivo pero con valores 3 y 4 veces menor que en los 2 pacientes del grupo control, donde este se elevó