Prevalencia de blastocystis hominis en muestra de materia fecal humana

51 p.Blastocystis hominis es un protozoo causante potencial de enfermedades gastrointestinales. Ha sido encontrado en personas de ambos sexos y de todos los grupos etarios, siendo considerado el protozoo intestinal más común en el mundo, con una prevalencia cercana al 50% en los países en vías de desarrollo. Se desea determinar la prevalencia de Blastocystis hominis en muestras de materia fecal humana. Se analizaron 472 muestras de heces de habitantes de la comuna de Molina, VII Región del Maule, Chile. A las muestras se les realizó examen coproparasitológico a través del Método de Burrows (PAF). Los resultados indicaron una prevalencia del 30.9 % de parasitación por Blastocystis hominis, existiendo una mayor prevalencia en el sexo femenino (57.5%) que en el sexo masculino (42.5%)

Nanosuspensions: particle size reduction as tool to improve lipophilic drugs bioavailability

En los últimos años, las nanosuspensiones han sido objeto de numerosos estudios con el n de evaluar sus propiedades biofarmacéuticas, demostrando en muchos casos valiosas ventajas frente a las formulaciones utilizadas convencionalmente. El uso de esta novedosa tecnología ha permitido el desarrollo de formas farmacéuticas para ser administradas por diferentes vías y también su aplicación ha demostrado ventajas en el desarrollo de estudios toxicológicos. En el presente trabajo se plantea una revisión de los aportes que brinda la obtención de partículas nanométricas de principios activos a la tecnología farmacéutica, los procesos de obtención de las mismas, así como su caracterización y principales aplicaciones en diferentes vías de administración de fármacos.In recent years, nanosuspensions have been subject of numerous studies in order to evaluate their biopharmaceutical properties, demonstrating in many cases valuable advantages over the conventional formulations. The application of this innovative technology has allowed the development of pharmaceutical dosage forms designed to be administrated by di erent routes, and its application has also demonstrated some advantages in the development of toxicological studies. This paper presents a review of the contributions that nanometric particles provide to the pharmaceutical technology area, the design and formulation procedures, characterization studies and principal applications.Fil: Starkloff, Walter Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biologia, Bioquimica y Farmacia. Catedra de Control de Calidad de Medicamentos; ArgentinaFil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; ArgentinaFil: Gonzalez Vidal, Noelia Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biologia, Bioquimica y Farmacia. Catedra de Control de Calidad de Medicamentos; Argentin

Rede iberoamericana de programas pós-consumo de medicamentos: passado, presente e futuro

Contamination by pharmaceuticals is a worldwide concern. Several studies have shown the deleterious effect that these products cause to ecosystems, including human beings. Among the strategies proposed to mitigate this problem are post- consumer drug management programs, mostly based on the concepts of Corporate Social Responsibility, Circular Economy, and Reverse Logistics. Four of these programs stand out, which have been successfully installed in Colombia (Punto Azul), Spain (SIGRE), Mexico (SINGREM) and Portugal (VALORMED). Together they conform the Ibero-American Network of Post-Consumer Drug Programs. This paper provides an overview of the origins of these programs, their current situation, and future projections.La contaminación por residuos farmacéuticos es una preocupación a nivel mundial. Diversos estudios han demostrado el efecto deletéreo que estos productos ocasionan sobre los ecosistemas en general, incluyendo los seres humanos. Entre las estrategias propuestas para mitigar esta problemática figuran los programas de gestión posconsumo de medicamentos, basados, en su mayoría, en conceptos de Responsabilidad Social Empresaria, Economía Circular y Logística Inversa. De tales programas se destacan cuatro, que han sido instalados con éxito, en Colombia (Punto Azul), España (SIGRE), México (SINGREM) y Portugal (VALORMED). En forma conjunta integran la Red Iberoamericana de Programas Posconsumo de Medicamentos. En este trabajo se brinda un panorama de los orígenes de estos programas, su situación actual y las proyecciones futuras.A contaminação por resíduos farmacêuticos é uma preocupação mundial. Vários estudos têm mostrado o efeito deletério que esses produtos causam nos ecossistemas em geral, inclusive no ser humano. Entre as estratégias propostas para mitigar esse problema estão os programas de gestão de medicamentos pós-consumo, em sua maioria baseados nos conceitos de Responsabilidade Social Corporativa, Economia Circular e Logística Reversa. Destacam-se quatro desses programas, implantados com sucesso na Colômbia (Punto Azul), Espanha (SIGRE), México (SINGREM) e Portugal (VALORMED). Juntos, eles compõem a Rede Ibero-Americana de Programas Pós-Consumo de Medicamentos. Este artigo fornece uma visão geral sobre as origens desses programas, sua situação atual e projeções futuras

Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial

Background: The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. Methods: Postmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360 gene panel, which includes 752 genes and 32 signatures. Results: Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (- 73.2%) was numerically higher compared to LTZ (- 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. Conclusions: Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum(ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPK alpha 1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.Peer reviewe

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

Gestão de medicamentos pós-consumo na Argentina: cenário local diante do contexto internacional

The increased life expectancy and the aged population have contributed to the prolonged use of drugs. Consequently, one negative result is the amount of pharmaceutical wastes, discarded in each home, either because they are expired, damaged or in disused. In order to prevent environmental damages, it is essential to eliminate pharmaceutical wastes properly since they have a direct or indirect impact on people’s health. That is the reason why many countries often include environmental policies in their agendas with the aim of mitigating pharmaceutical pollution’s consequences. These plans, which are coordinated by local health authorities, set out to reduce the risk of environmental contamination as well as the impact on public health. In Argentina, by contrast, there is a legal vacuum related to the approach of pharmaceutical pollution. The obtained results allow the detection of 55 specific actions, promoted by various entities, ranging from awareness campaigns to the implementation of specific post-consumption management instruments. In view of all the research on the subject by civil and professional organizations, it is not possible to solve this problematic situation without the political commitment to establish national policies, that after being adopted, provide benefits that last over time.A medida que aumenta la esperanza de vida y la población envejece, también lo hace el uso de medicamentos consumidos por ella. Una de las consecuencias negativas de esta demanda es la cantidad de residuos farmacéuticos, desechados en los domicilios ya sea por encontrarse vencidos, dañados o en desuso. Su adecuada eliminación resulta fundamental a fin de evitar daños al ambiente, que de manera directa o indirecta impacta en la salud humana. Por esta razón, los países suelen incluir en sus agendas las políticas ambientales que buscan mitigar las consecuencias de esta farmacontaminación. Así se implementan programas que suelen ser coordinados por las autoridades sanitarias locales, los cuales tienen como objetivo reducir el riesgo de contaminación del medio ambiente y la afectación de la salud pública. En Argentina, en cambio, se evidencia un vacío legal en lo concerniente al abordaje de la farmacontaminación. Los resultados obtenidos en este trabajo permiten detectar 55 acciones concretas, promovidas por diversos entes, que van desde la concientización poblacional hasta la implementación de herramientas puntuales de gestión posconsumo. En virtud de los resultados obtenidos a partir de iniciativas emprendidas por organizaciones civiles y profesionales, se denota que para resolver esta problemática se requiere el compromiso político por parte de autoridades gubernamentales para instaurar políticas nacionales que, al ser acatadas, produzcan beneficios que perduren en el tiempo.Como aumento da expectativa de vida aumenta e a população envelhece, também aumenta o uso de drogas consumidas por ela. Uma das consequências negativas dessa demanda é a quantidade de resíduos farmacêuticos, descartados nas residências, seja por prazo de validade, danificado ou em desuso. Seu descarte adequado é fundamental para evitar danos ao meio ambiente que impactem direta ou indiretamente a saúde humana. Por esse motivo os países costumam incluir em suas agendas políticas ambientais que buscam mitigar as consequências dessa fármacopoluição. Assim são implementados programas que geralmente são coordenados pelas autoridades locais de saúde, cujo objetivo é reduzir o risco de contaminação ambiental e o impacto na saúde pública. Na Argentina, por outro lado, há indícios de um vácuo legal quanto à abordagem da fármacopoluição. Os resultados obtidos neste trabalho permitem detectar 55 ações específicas, promovidas por diversas entidades, que vão desde ações de sensibilização da população até à implementação de ferramentas específicas de gestão pós-consumo. Em virtude dos resultados obtidos com as iniciativas empreendidas pelas organizações civis e profissionais, para solucionar esse problema, é necessário o compromisso político das autoridades governamentais para o estabelecimento de políticas nacionais que, quando aderidas, produzem benefícios que perduram no tempo

Celiac Disease: Historical Standpoint, New Perspectives of Treatments and Contemporary Research Techniques

Celiac disease (CD) is an inflammatory syndrome that affects mainly the intestine, but also other organs. This ailment is also affected by the physicochemical behavior of gluten as such. From the medical standpoint, this pathology results from a combination of genetic and environmental factors. At the same time, gliadin (the alcohol-soluble fraction of gluten) along with other related oligomers, such as 33-gliadin, present high immunogenicity and are responsible for triggering of this disease. Within CD characterization, there are mainly two different approaches to carry out this study; one focuses on its chronic phase, while the other deals with its initial stages. Although the chronic phase of CD has been well characterized, the initiation of the inflammatory process is still unclear. As this process is apparently related to the aggregation of the oligomers involved in CD, the initiation of the disease could be explained by means of clarifying their self-assembly behavior. Thus, this work addresses the clinical explanation, within the chronic approach, attempting to combine it with the physicochemical techniques used for characterization of proteins aggregates as well.Fil: Benedini, Luciano Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: González Vidal, Noelia Luján. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Gonzalez, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

Orphan Formulations in Pediatric Schistosomiasis Treatment: Development and Characterization of Praziquantel Nanoparticle—Loaded Powders for Reconstitution

Praziquantel is a broad spectrum antihelmintic agent and represents the drug of choice for the treatment of schistosomiasis. However, its low aqueous solubility and strong bitter taste highly affect the bioavailability and compliance in pediatric patients. Thus, the purpose of this study was to develop a dry nanosuspension, by a combination of high-pressure homogenization and spray drying, intended for redispersion in a pleasant taste vehicle for extemporaneous use. Three formulations, varying stabilizers to drug ratio, were developed and characterized in terms of particle size distribution, crystallinity, morphology, in vitro dissolution, and sedimentation-redispersibility behavior. A significant reduction in particle size was achieved after the high-pressure homogenization process, and the nanoparticles were further microencapsulated by spray drying technique. The redispersed dried powders exhibited a conserved particle size distribution (in the nanometric range) and certain crystallinity extent, with satisfactory redispersion ability. Besides, the enhancement of the dissolution performance obtained after comminution was conserved, even after drying and redispersion of the extemporaneous powdered formulation. In conclusion, the developed nanoparticle-loaded powders comprise an interesting tool for the administration of praziquantel to preschool-age children.Fil: Gonzalez, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Ramírez Rigo, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: González Vidal, Noelia Luján. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentin

Praziquantel systems with improved dissolution rate obtained by high pressure homogenization

Praziquantel (PZQ), an antihelmintic agent commonly administered to humans and cattle, has low aqueous solubility, which compromises its bioavailability and efficacy. The purpose of this study was to develop a new formulation, inorder to improve PZQ dissolution rate. PZQ dispersions have been developed by high-pressure homogenization (HPH) using different stabilizers, selected upon PZQ saturation solubility. After the screening, two promising formulations were developed, combining poloxamer 188 with polyvinylpyrrolidone or maltodextrin. Characterization studies including particle size distribution, crystallinity, morphology, drug content, and in vitro dissolution profiles, were performed over selected formulations. The scanning electronic micrographs revealed that the morphology of suspended particles corresponded to elongated shapes, with an average particle size close to the micron range. X-ray powder diffractometry and differential scanning calorimetry results confirmed the drug crystallinity, before and after the HPH process. Besides, differential scanning calorimetry revealed the absence of interactions between PZQ and excipients. The dissolution rate of PZQ dispersions was significantly enhanced compared with raw PZQ, either in phosphate buffer or hydrochloric acid, mainly due to particle size reduction, thus improved saturation solubility.Fil: Gonzalez, María Alejandra. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Ramírez Rigo, María Veronica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: González Vidal, Noelia Luján. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentin