Zinc Oxide Nanoparticles and Photodynamic Therapy for the Treatment of B-chronic Lymphocytic Leukemia

The generation of singlet oxygen (SO) in the presence of specific photosensitizers (PS) or semiconductor nanoparticles (NPs) and its application in photodynamic therapy (PDT) has great interest for the development of new cancer therapies. Our work focused on the identification of factors leading to the enhancement of B-Chronic Lymphocytic Leukemia (B-CLL) intracellular SO production and cell killing using Manganese (Mn) doped and undoped Zinc Oxide (ZnO) NPs as potential photosensitizers with and without PDT. Mn can enhance ZnO NPs generation of SO by targeted cells. Multi drug resistant B-Chronic Lymphocytic Leukemia (B-CLL) cells spontaneously produce high amounts of Reactive Oxygen Species (ROS) having an altered redox state in relation to that of normal B lymphocytes. These little variations of its SO intracellular concentrations could allow ZnO NPs to execute specific deadly programs against these leukemic cells with no significant damage to normal lymphocytes. A 0.5% Mn Doped ZnO NP was finally selected for further probes as it had the best killing activity in fludarabine resistant B-CLL cells, especially when combined with PDT. This could be an innovative specific therapy against resistant B-CLL probably contributing in the near future for the definitive benefit of these bad prognostic patients

Budgetary Impact of Covering “Me-Too” Drugs from Social Security: Buenos Aires State Case Report

The majority of new drugs registered at Health Global Market are not considered real innovations and due to their chemical structure similarity of reference’s group drug, they are known as “me-too”. These “me too” drugs usually has no additional therapeutic benefits but greatly increasing treatment cost. PURPOSE: To demonstrate the economic impact in Social Security budget by covering “me too” medicines. METHODS: An epidemiological-descriptive-analytical study was performed in order to analyze the burden of anti-hypertensive prescription from patients under coverage by Buenos Aires State Social Security (SS). Two types of medicines were compared: “pioneer/classic” or “me-too”. Variables considered were: medicine type, therapeutical group, global costs, burden for SS and for patients. RESULTS: From 185865 patients with hypertension treated; in 121748 of the cases the strategy was monotherapy while 64117 of them received at least two or more medicines. 189714 were reference drugs while 64393 were considered “me-too”. In average, “me-too” drugs were 41.23% more expensive than classical treatment. The percentage covered by SS varies according to the medicines (between 45 to 51%) and patients must complete the amount of money remaining from their pockets. Paradoxically, the percentage covered by SS of some “me-too” were greater than coverage for most classic medications of each group. CONCLUSIONS: By only choosing the drug of reference from each therapeutical group with has proven effectiveness, the Social Security might increase the coverage to 100% of the cost of all anti-hypertensive treatment for all patients; and even that, still saving almost 2 million dollars per yea

Could Metabolic Syndrome, Lipodystrophy, and Aging Be Mesenchymal Stem Cell Exhaustion Syndromes?

One of the most important and complex diseases ofmodern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development ofmetabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stemcell exhaustion syndrome (SCES). Themain outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies

Feasibility investigation of allogeneic endometrial regenerative cells

Endometrial Regenerative Cells (ERC) are a population of mesenchymal-like stem cells having pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies suggest ERC are immune privileged and in certain situations actively suppress ongoing immune responses. In this paper we describe the production of clinical grade ERC and initial safety experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case with the longest follow up, of more than one year, revealed no immunological reactions or treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC administration and support further studies with this novel stem cell type

Enfoque del tratamiento de la Salud Mental en los últimos 70 años en Bs As, Argentina

Objetivos: evaluar el impacto terapéutico y costos asociados a tratamientos de patología mental en los últimos 70 años. Metodología: estudio retrospectivo-descriptivo con etapa analítica en el cual se evaluaron historias clínicas de pacientes internados en Institución de Salud Mental de Buenos Aires. Las variables analizadas fueron: edad, sexo, motivo de internación, promedio de estadía, re-internaciones, número y tipo de medicamentos por década, resultados en términos de mejoría clínica, costo de medicamentos e internaciones en cada década

Could Metabolic Syndrome, Lipodystrophy, and Aging Be Mesenchymal Stem Cell Exhaustion Syndromes?

One of the most important and complex diseases ofmodern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development ofmetabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stemcell exhaustion syndrome (SCES). Themain outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies

Remédios retirados em outros países devido a problemas de segurança: Devem continuar presentes no mercado farmacêutico argentino?

Introduction: Numerous medicines have been withdrawn from the market because of the risks of serious adverse effects. The objective of this study was to identify in the Argentine pharmaceutical market (APM) the presence of medicines withdrawn in other countries due to safety problems, to analyze the information on their risks and to propose recommendations. Method: observational, descriptive study that explored the presence in the APM, until May 2021, of 462 medicines withdrawn in other countries. Those medicines on this list that are present in the APM and that are not currently authorized in countries with high sanitary surveillance were studied. Results: 17 medicines are still present in the APM, one over-the-counter. The package insert for 11 of the 17 medicines does not mention the adverse effects that led to their withdrawal. It was considered that the permanence in the APM of 16 of them should be reassessed. Conclusions: recommendations are made on actions to be taken by the regulatory authorities with the 17 medicines already present in the APM.Introducción: Numerosos fármacos han sido retirados del mercado por sus riesgos de efectos adversos graves. El objetivo de este trabajo fue identificar en el mercado farmacéutico argentino (MFA) la presencia de medicamentos retirados en otros países por problemas de seguridad, analizar información sobre sus riesgos y proponer recomendaciones. Método: estudio observacional, descriptivo que exploró la presencia en el MFA, hasta mayo de 2021, de 462 medicamentos retirados en otros países. Se estudiaron aquellos medicamentos de esta lista presentes en el MFA y que no estuvieran autorizados actualmente en países de alta vigilancia sanitaria. Resultados:17 medicamentos siguen presentes en el MFA, uno de venta libre.  El prospecto de 11 de los 17 fármacos no menciona los efectos adversos que motivaron su retiro. Se consideró que la permanencia en el MFA de 16 de ellos debería ser reevaluada. Conclusiones: se realizan recomendaciones sobre acciones a tomar por las autoridades reguladoras con los 17 medicamentos aún presentes en el MFA.Introdução: Vários medicamentos foram retirados do mercado devidoaos riscos de efeitos adversos graves. O objetivo deste estudo foi identificar no mercado farmacêutico argentino (MFA) a presença de medicamentos retirados em outros países por problemas de segurança, analisarinformações sobre seus riscos e proporrecomendações. Método:estudo observacional, descritivo que explorou a presença no MFA, até maio de 2021, de 462 medicamentos retirados em outros países. Foramestudados os medicamentos desta lista que estão presentes no MFA e que atualmentenãosão autorizados em países com alta vigilânciasanitária. Resultados: 17 medicamentos aindaestão presentes no MFA, umsemprescrição. A bula de 11 dos 17 medicamentos não menciona os efeitos adversos que levaram à sua retirada. Considerou-se que a permanência no MFA de 16 deles deveria ser reavaliada. Conclusões:sãofeitasrecomendações sobre as ações a serem tomadas pelas autoridades reguladoras com os 17 medicamentosaindapresentes no MFA

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO