Gestión de riesgos aplicado al diseño de un nuevo proceso productivo de un inmunoterapéutico del Centro de Ingeniería Genética y Biotecnología / Risk management applied to the design of a new production process for an immunotherapeutic from the Center for Genetic Engineering and Biotechnology

El estudio expone las acciones dirigidas a la reducción de los riesgos en el diseño de un nuevo proceso de producción del ingrediente farmacéutico activo de un inmunoterapéutico producido en el Centro de Ingeniería Genética y Biotecnología. El análisis modal de fallas y efectos fue conducido por un equipo multidisciplinario del referido centro. La administración de riesgos a la calidad se aplicó a la tecnología de obtención de una proteína recombinante con uso diagnóstico que se proponía transferir a la Dirección de Desarrollo Tecnológico. El riesgo en el diseño de un nuevo proceso de producción evaluó las fallas de mayor influencia en el bajo recobrado y el incumplimiento de las especificaciones de calidad del inmunoterapéutico. Las causas potenciales de estos fallas fueron: la insuficiente cantidad de viales de los bancos de células, el medio de cultivo complejo con componentes de origen bovino, la incorrecta manipulación de las muestras por los operarios, el uso de equipamiento no adecuado, los parámetros de operación (agitación, pH y conductividad) fuera de límites de especificación con efecto sobre la pureza por el alto porcentaje de contaminantes del hospedero; así como, un medio filtrante inadecuado unido a una incorrecta preparación del sistema de filtración redundantes en un producto no estéril. Las acciones llevaron a modificaciones en la tecnología propuesta por la Dirección de Investigaciones Biomédicas que permitió el diseño de un nuevo proceso productivo para un biofarmacéutico destinado al tratamiento de enfermedades virales crónicas(AU)

The study aimed at reducing risks in the design of a new production process for the active pharmaceutical ingredient of an immunotherapeutic produced at the Center for Genetic Engineering and Biotechnology. The failure mode and effects analysis were conducted by a multidisciplinary team from the center. Quality risk management was applied to the technology for obtaining a recombinant protein for diagnostic use that was proposed to be transferred to Technological Development Division. The risk analyses evaluated the greatest influence on low recovery and non-compliance with the immunotherapeutic quality specifications. The potential causes of the failures were: the insufficient number of vials in cell banks, the complex culture medium with components of bovine origin, the samples handling errors by the operators, the use of inappropriate equipment, the parameters of operation (agitation, pH and conductivity) outside specification limits affecting purity due to the high percentage of contaminants from the host; as well as, the inadequate filtering medium together with an incorrect preparation of the redundant filtration system in a non-sterile product. The actions could modify the technology proposed by Biomedical Research Division that allowed the design of a new production process of a biopharmaceutical product for the treatment of chronic viral diseases(AU)

Impacto del uso de PCR múltiple en diagnóstico etiológico y tratamiento de infecciones respiratorias agudas en un hospital privado del norte del país / Impact of the use of multiplex PCR on etiological diagnosis and treatment of acute respiratory infections in a private hospital of the north of the country

Resumen Antecedentes y objetivo: Las enfermedades del sistema respiratorio son causa frecuente de prescripción de antibióticos. Actualmente se emplean nuevas tecnologías para su diagnóstico como el FilmArray Respiratory Panel. El objetivo de este estudio es identificar la correlación entre el diagnóstico y tratamiento de infecciones de vías respiratorias con el resultado de PCR para virus respiratorios. Material y métodos: Estudio descriptivo, transversal, retrospectivo, se incluyeron 134 pacientes atendidos en el Hospital Christus Muguerza en Saltillo, Coahuila. Para todos los casos se analizaron los resultados del panel y el tratamiento que recibieron los pacientes. Resultados: El 58 % recibió tratamiento antibiótico a su ingreso, el 13 % tratamiento combinado (antibiótico + antiviral), 27 % recibió tratamiento sintomático y el 2 % fue tratado con antiviral de primera instancia. Posterior al resultado el 38 % continuó con antibiótico, el 30 % con antibiótico y antiviral, 13.8 % se manejó con antiviral y el 18.2 % con tratamiento sintomático. Conclusión: A pesar de la alerta mundial por la resistencia a los antimicrobianos se sigue tratando a los pacientes con antibióticos, por una situación que se cree está influenciada por varios factores.

Abstract Background and objective: Respiratory system diseases represent one of the leading cause of prescription of antibiotics. At present, new technologies for the diagnosis are being used, including the FilmArray Respiratory Panel. The objective was to identify the correlation between the diagnosis and treatment of respiratory tract infections with the result of PCR for respiratory viruses. Material and methods: Descriptive, cross-sectional, restrospective study. 134 patients were included treated at the Christus Muguerza Hospital in Saltillo, Coahuila. For all cases, the positive results of this test and the treatment patients received were analyzed. Results: 58 % received antibiotic treatment at admission, 13 % received combined treatment (antibiotic + antiviral), 27 % received symptomatic treatment since their admission and 2 % whit antiviral. After receiving a positive result for respiratory viruses, 38 % continued with antibiotics, 30 % with antibiotics and antivirals, 13.8 % only managed with antivirals and 18.2% with symptomatic treatment. Conclusion: Although we are currently on global alert for resistance to antibiotics, there is a lack of awareness about the prescription of antibiotics, due to a situation which is believed to be influenced by several factors.

Preprocesamiento de los fármacos antivirales candidatos contra COVID-19 en modelos de SARS cov2. Objetivos / Preprocessing of the candidate antiviral drugs against COVID-19 in models of SARS cov2 targets

Although many viral infections are self-limiting, other are real health challenges like COVID-19 since many viruses possess just few drug gable targets to be treated with small drug molecules. Corona virus genome encodes for up to 17 main proteins. Orf1ab encodes for polyprotein. COVID-19 structural proteins are the spike S, membrane M, envelope E and the nucleocapsid N protein while other are non-structural proteins designated as NSP1-13 for non-structural proteins. Among NSP the most important corona virus targets for developing antiviral drugs are the papain-like protease, PDB ID: 6m03 and RNA polymerase NSP12, PDB ID: 6nur. NCBI, NIH Genbank, Uniprot, PDB, DrugBank, ChemSpider databases and bioinformatics editor softwares like ICM Mol soft pro and Swiss Dock were used in addition to the in vitro lab model of viral protease were integrated to retrieve and analyze corona virus targets and to select the candidate ligands in an attempt to evaluate the inhibitory efficacy of different experimental and approved drugs which were further optimized and searched for the highly similar approved drug. This step aims to adopt drug repurposing to speed the development of antiviral drugs and recommend rational in vivo and clinical studies. After COVID-19 targets had been analyzed the drugs that shared > 70% similarity to the binding sites of those targets were reversin, pentagastrin, remdesivir, norfloxacin and nitazoxanide against COVID-19 papain-like protease whereas benzyl glutathione, lopinavir and hydroxymethylglutathione against RNA polymerase. The anti-resistance reversin showed the highest inhibitory efficacy against COVID-19 papain-like protease as indicated by the ligand-protease binding energy with Mol soft pro analysis. The calculated inhibitory binding was -137.30 kJ/mol z > 1.9 as compared with the tetrazapentadecanoate -129.57 kJ/mol z = 4.0, whereas remdesivir, pentagastrin, nitazoxanide and norfloxacin had a moderate antiprotease activity (>- 100 kJ/mol). Norfloxacin shoresults showed a slight consistency between in vitro and in silico models. Although benzyl glutathione is an experimental compound, however it had the highest RNA polymerase inhibiting efficacy with -129 kJ/mol binding energy which is even higher than lopinavir and Favinavir. From the overall results, reversin, oligopeptides, quinolones and antiviral drugs may widen the treatment options for COVID-19 if further evaluated in clinical studies

La sostenibilidad del sistema de salud y el mercado farmacéutico: Una interacción permanente entre el costo de los medicamentos, el sistema de patentes y la atención a las enfermedades / The sustainability of the health system and the pharmaceutical market: A permanent interaction between the cost of medications, the patent system, and disease care

RESUMEN Ante la amenaza latente de futuras pandemias, este estudio tiene como objetivo analizar -desde el eje de los medicamentos- la sostenibilidad del sistema sanitario, la cobertura, la eficiencia del gasto y su vinculación al sistema de patentes farmacéuticas. En este marco, el sistema de patentes farmacéuticas adquiere un papel determinante, dado que fomentar su existencia estimula la producción de investigación pero, a su vez, su existencia no suscita un rápido avance, debido al desarrollo legislativo protector que han tenido las patentes y que ha dado lugar a un acomodamiento de la industria. Como la industria farmacéutica ha conseguido extender la duración de patentes y evitar la incorporación de genéricos, se analiza la influencia de las patentes farmacéuticas que ha dado lugar a reflexionar acerca de la posibilidad de consorciar esfuerzos realizando alianzas entre varias empresas y el sector público para afrontar los retos que plantean nuevas enfermedades producidas por virus que dan lugar a epidemias y pandemias.

ABSTRACT Taking into account the latent threat of future pandemics, the objective of this study is to analyze - particularly with respect to medications - the sustainability of the health system, healthcare coverage, budgetary efficiency, and connections with the pharmaceutical patent system. In this context, the pharmaceutical patent system acts as a determining factor, given that promoting its existence stimulates the production of research, but in turn its existence stands in the way of rapid advancements, primarily due to the development of protective legislation concerning patents, which has largely accommodated the industry. Given that the pharmaceutical industry has managed to extend the duration of patents and avoid the incorporation of generics, our analysis focuses on the influence of pharmaceutical patents; this influence has led to reflection on the possibility of combining efforts by forging alliances between numerous companies and the public sector in order to face the challenges posed by new diseases caused by viruses that give rise to epidemics and pandemics.

Rinossinusite aguda / Acute rhinosinusitis

Objetivos: revisar a prevalência, a etiologia, o diagnóstico e o tratamento da rinossinusite aguda. A rinossinusite aguda é uma doença comum de prevalência mundial, caracterizada por uma inflamação da cavidade nasal e dos seios paranasais, podendo ter origem fúngica, viral ou bacteriana. Os sintomas são principalmente obstrução e secreção nasal, porém a sintomatologia pode ser ampla. Consequentemente, a correta identificação e manejo torna essa patologia um desafio na prática clínica. Metodologia: Foi realizado uma busca nas bases de dados Medline/ Pubmed e LILACS no mês de maio de 2018, incluindo artigos publicados em inglês ou português nos últimos 5 anos. Foram utilizados os seguintes descritores: "acute rhinosinusitis", "rhinitis" e "sinusitis". Os artigos foram selecionados com busca direta, considerando relevância do tema à proposta e fator de impacto. Resultados: De 228 publicações, 10 foram selecionadas, demonstrando que a rinossinusite aguda é uma doença cuja incidência ainda não está bem definida, mas é maior em indivíduos com idade entre 12 e 17 anos em relação à população geral, com prevalência de etiologia viral. Conclusão: A rinossinusite aguda é uma doença com alta incidência. O diagnóstico é predominantemente clínico, mas em casos restritos há exames de imagem, sendo o tratamento sempre sintomático.

Objectives: To review the prevalence, etiology, diagnosis and treatment of acute rhinosinusitis. Acute rhinosinusitis is a common global disease characterized by inflammation of the nasal cavity and paranasal sinuses, which may be of fungal, viral or bacterial origin. The symptoms are mainly obstruction and nasal secretion, but the symptomatology can be ample. Methodology: The search was performed in the Medline / Pubmed and LILACS databases in May 2018, including articles published in English or Portuguese in the last 5 years. The following descriptors were used: "acute rhinosinusitis", "rhinitis" and "sinusitis". The articles were selected with direct search, considering relevance of the theme to the proposal and impact factor. Results: Of 228 publications, 10 were selected, demonstrating that acute rhinosinusitis is a disease whose incidence is still not well defined, but is higher in individuals aged 12 to 17 years in relation to the general population, with a prevalence of viral etiology. Conclusion: Acute rhinosinusitis is a disease with a high incidence. The diagnosis is predominantly clinical, but in restricted cases there are imaging tests, and the treatment is always symptomatic.

Use of minocycline in viral infections.

Repurposing of old drugs is a useful concept as it helps to minimize costs associated with the research and development of a new drug. Minocycline, a common second generation antibiotic, has been shown to possess several other beneficial effects other than its intended uses. The antiviral role of minocycline has generated considerable interest from the last decade. It was first shown to be beneficial in preventing human immunodeficiency virus (HIV) infections and later it was reported to improve cognitive deficiencies associate with neuroAIDS. However, its antiviral efficacies are not limited to retroviruses alone. In animal models or in vitro systems of flaviviral infections (especially Japanese encephalitis virus), minocycline has been shown to be highly effective. However, not all effects are based on direct inhibition of viral replication. The general anti-inflammatory and immunomodulatory properties of minocycline are also responsible in part, in imparting the protective effects. Owing to the fact that minocycline is well tolerated by most people and that the drug has nearly 40 years history of usage, it is an exciting prospect to try out in other viral infections.

Miocarditis viral en el adulto / Viral myocarditis in the adult

La miocarditis viral es resultado de una inflamación del miocardio provocada por diferentes virus. Esta enfermedad cardíaca constituye sin duda una urgencia cardiovascular en el adulto por las complicaciones que ocasiona. El cuadro clínico se caracteriza por arritmias e insuficiencia cardíaca que pueden conducir a la muerte. La secuela más frecuente de la miocarditis viral a largo plazo es la miocardiopatía dilatada. En el presente trabajo se revisa etiología, fisiopatología, sintomatología, diagnóstico y tratamiento de la miocarditis viral en el adulto

Viral myocarditis is the result of a myocardial inflammation provoked by different viruses. This cardiac disease is doubtless a cardiovascular urgency in the adult due to its complications. The clinical picture is characterized by arrhythmias and cardiac failure that may to lead to death. The more frequent long-term myocarditis sequela is the dilated myocardiopathy. In present paper etiology, pathophysiology, symptomatology, diagnosis and treatment of viral myocarditis in the adult are reviewed

Probióticos en diarrea aguda infecciosa / Probiotics in acute infectious diarrhea

Background: Acute infectious diarrhea in children represents a worldwide problem and it relates to desnutrition, morbility and death. Objective: Determine the usefulness of probiotics in the treatment of acute infectious diarrhea in children by reviewing the scientific information available in the form of meta-analysis. Methods: A detailed search was performed in electronic databases. Four of the articles found met inclusion criteria. Results: The four meta-analysis studied demonstrated that the administration of probiotics in children with acute infectious diarrhea decreased the episode duration in approximately one day with minimal adverse events. Conclusions: Despite methodological limitations of the analysed articles, the studies showed the same trend towards observing a benefit in the use of probiotics in acute infectious diarrhea in children. The latter supports the consistency of this association. In general, the use of probiotics in children with acute infectious diarrhea would be useful in general practice reducing diarrhea duration in approximately one day.

Antecedentes: La diarrea aguda infecciosa en niños constituye un problema a nivel mundial y se traduce en desnutrición, morbilidad y muerte. Objetivos: Determinar la utilidad de los probióticos en el tratamiento de la diarrea aguda infecciosa en los niños mediante la revisión de la información científica disponible en forma de meta-análisis. Material y Métodos: Se realizó una búsqueda detallada en bases de datos electrónicas de uso frecuente. Cuatro de los artículos encontrados cumplían con los criterios de inclusión. Resultados: Los cuatro meta-análisis revisados evidenciaron que la administración de probióticos en niños con diarrea aguda infecciosa disminuía la duración del cuadro en aproximadamente un día con mínimos efectos adversos. Conclusiones: A pesar de las limitaciones metodológicas de los trabajos analizados, la mayoría de los estudios presentan una misma tendencia al observar beneficio en el uso de los probióticos en diarrea aguda infecciosa en niños. Lo anterior le otorga mayor consistencia a la asociación. En general, el uso de probióticos en niños con diarrea aguda infecciosa sería útil en la práctica clínica diaria, disminuyendo la duración de la diarrea en aproximadamente un día.

Chloroquine: novel uses & manifestations.

Chloroquine (CHQ) is a cheap, relatively well tolerated drug initially developed for the treatment of malaria in the 1930s. CHQ has, however, since accrued a plethora of uses in the treatment and amelioration of several other diseases and conditions because of its lysosomotropic properties. It also has characteristic physiological and systemic effects. This review gives an overview of the history and pharmacology of CHQ, and progresses to consider some of the mechanisms that may underlie its biochemical and physiological effects. Additionally, an overview of some of the novel uses of CHQ in the treatment of viral infections and cancer are presented. The antimalarial mechanisms of CHQ were not discussed in this review. The message is that CHQ, despite its welldocumented toxicity and adverse side effects may have important future uses that are associated with its lysosomotropic and immunomodulatory mechanisms. The possibility exists therefore that CHQ might be re-introduced into regular malaria treatment.

Antibiotics for the empirical treatment of acute infectious diarrhea in children

While the routine use of antibiotics for infectious diarrhea in children must be avoided, because it brings little benefit in most cases and is associated with the risk of increasing antimicrobial resistance, selected cases may require antimicrobial therapy, and the choice of the antimicrobial agent often has to be made empirically. Physicians prescribing antimicrobials in such a setting have not only to be aware of the most likely pathogens, but also of their characteristic antimicrobial susceptibility pattern and the safety profile of the various drugs. We reviewed the literature on the use of ampicillin, beta-lactamase inhibitors, trimethoprim-sulfamethoxazole, chloramphenicol, tetracyclines, nalidixic acid, fluoroquinolones, third-generation cephalosporins, macrolides, metronidazole and malabsorbed agents in the setting of acute infectious diarrhea, and we evaluated the available information, seeking to apply it to empirical use, highlighting clinically-useful pharmacological information and patients' and pathogens' characteristics that must be taken into account for decisions about antimicrobial therapy.

New antiviral agents.

During the last three decades, a better understanding of viral replication and disease states caused by viral infections have led to the development of newer antiviral agents with enhanced activity and better tolerability. This review focuses on newer systemic and topical antiviral agents that are used in treatment of herpes viruses including herpes simplex type-1 (HSV-1) and type-2 (HSV-2), varicella-zoster virus (VZV) and cytomegalovirus CMV) as well as the human papilloma virus (HPV). Included in this article are the agents famciclovir, penciclovir, valganciclovir, imiquimod, docosanole and brivudin.

Antivirugrama: ¿ciencia ficción o realidad? / Antivirugram: science fiction or reality?

El panorama creciente de infecciones virales severas, que amenazan la vida de los pacientes, la disponibilidad de técnicas de diagnósticos virológico rápido y los conocimientos patogénicos más acabados con biología molecular, han estimulado el desarrollo explosivo de fármacos antivirales. Como consecuencia nace la necesidad de incorporar a las decisiones clínicas la evaluación in vitro de algunos de estos medicamentos y la aparición de resistencia durante tratamientos prolongados, como ha sido el dramático caso de la infección por VIH/SIDA. Se revisan los antivirales licenciados para el uso médico y el grado de aplicación clínica de los estudios de susceptibilidad in vitro alcanzado en la actualidad