Morphometric study of myocardial changes during doxorubicin-induced cardiomyopathy in mice

Doxorubicin (DOX) is one of the most effective anti-cancer drugs in oncology, but may cause a cumulative dose-dependent cardiomyopathy in a number of cancer patients. The effect of DOX on the heart was studied in mice treated with i.v. injections of 2 mg/kg by measuring morphometric parameters, including nuclear index (number of non-myocytes/number of myocyte nuclei), reticulin index (reticulin area/number of myocyte transsections), nuclear transsectional area, myocyte transsectional area, capillary index (number of capillaries/number of myocyte transsections) and capillary transsectional area. The highest significant difference between control mice and DOX-treated mice was observed immediately after the 12th dose of DOX except for the two capillary parameters. The highest level of significance for these two parameters was obtained 12 weeks after the end of DOX treatment. In contrast to the observations in rats, mice did not develop a nephrotic syndrome during treatment with DOX. The morphometric analysis of myocardial changes in mice, as a quantitative and objective method, seems to be a good model for comparative studies on cardiomyopathy induced by anthracycline analogues

Dynamics of antifolate transport via the reduced folate carrier and the membrane folate receptor in murine leukaemia cells in vitro and in vivo

Murine L1210 leukaemia cells expressing either the reduced folate carrier (RFC) or the membrane folate receptor (MFR) were studied in vitro and in vivo to assess the dynamics of membrane transport of two categories antifolates; folate-based inhibitors of dihydrofolate reductase (methotrexate, edatrexate, aminopterin, PT523, and PT644) and thymidylate synthase (TS) [CB3717, raltitrexed, plevitrexed (BGC9331), pemetrexed and GW1843]. The potency of in situ inhibition of TS was used as an endpoint to analyze the in vitro dynamics of RFC/ MFR-membrane transport of these antifolates. Both for L1210-RFC and L1210-MFR cells, the potency of in situ TS inhibition was closely correlated with increasing aYnities of these transporters for the antifolates (r = 0.64, P < 0.05 and r = ¡0.65, P < 0.05, respectively). Within the group of antifolates for which MFR had a low binding aYnity, those that had the ability to become polyglutamylated, were more potent inhibitors of TS in situ activity than non-polyglutamatable antifolates. In vivo activity of methotrexate, edatrexate, raltitrexed and pemetrexed was assessed in L1210-RFC and L1210-MFR bearing mice that were fed either a standard or a folate-deWcient chow. Dietary folate depletion signiWcantly reduced the MTD for methotrexate (sevenfold), edatrexate (sevenfold), raltitrexed (50-fold) and pemetrexed (150-fold). Based on increased life spans, antitumor eVects of methotrexate and edatrexate were markedly better in L1210-RFC bearing mice on the folate-deWcient chow (ILS: 455 and 544%, respectively) than on standard chow (ILS: 213 and 263%, respectively). No therapeutic eVects of methotrexate and edatrexate were observed for L1210-MFR bearing mice on either chow condition, which may be consistent with the low binding aYnity for MFR. Irrespective of the folate diet status, pemetrexed and raltitrexed were inactive against both L1210-RFC and L1210-MFR bearing mice, which may be due to high circulating plasma thymidine levels. Collectively, this study underscores that modulation of dietary folate status can provide a basis within which the therapeutic eVect of antifolates may be further improved

Impacts of a novel shellfishing gear on macrobenthos in a marine protected area: pump-scoop dredging in Poole Harbour, UK

Understanding the impact of bottom-fishing gears at various scales and intensities on habitats and species is necessary to inform management. In Poole Harbour, UK, a multiple use marine protected area, fishermen utilise a unique “pump-scoop” dredge to harvest the introduced Manila clam Ruditapes philippinarum. Managers need to balance the socio-economic benefits of the fishery with ecological concerns across the region, which has required a revision of by-laws that include both spatial and temporal measures. Within an operational fishery, we used a Before-After-Control-Impact sampling design to assess the impacts of pump-scoop dredging on benthic physical characteristics and community structure in an area where there was no dredging, an area newly opened to dredging and an area subject to high levels of historic dredging. A sampling grid was used in each area to best capture any fishing effort in the newly opened area. Core samples were taken to a depth of 30 cm within intertidal mudflats. A significant loss of fine sediments was observed in the site subject to high intensity dredging and a significant change in community structure also occurred in both dredged sites throughout the study period. In the newly opened site this was characterised by a relative increase in species richness, including increased abundance of annelid worms, notably Hediste diversicolor and Aphelochaeta marioni and a decline in the abundance of the bivalve mollusc Abra tenuis. These changes, albeit relatively small, are attributed to physical disturbance as a direct result of pump-scoop dredging, although no difference in the classification of the biotope of the site was observed. This is of particular interest to managers monitoring site condition within areas under the new bylaws as the Manila clam is spreading to other protected estuaries in the region

Clinical and epidemiological characteristics of 25 cases of COVID-19 treated at the Delgado Clinic in Lima

&nbsp;Objetivo: Presentar las características clínicas y epidemiológicas de los pacientes con COVID-19 atendidos en un hospital privado de Lima. Material y Métodos: Estudio descriptivo, retrospectivo y seccional. Se presenta a los 25 casos atendidos desde el día 9 de marzo al 27 de marzo del presente año, durante la pandemia actual, que fueron atendidos en el Departamento de Emergencia de la Clínica Delgado, Miraflores, Lima. Todos ellos fueron positivos para rRT-PCR para coronavirus, realizados en el Instituto Nacional de Salud. Resultados: Casos importados, 24% o primeros contactos de ellos, 48%. Doce (48%) fueron varones. La mediana de edad fue de 38 años (rango: 11-67 años) para varones y 44 años (rango: 33-71 años) para mujeres; y una mediana global de 40 años (rango: 11-71 años). Las manifestaciones clínicas fueron: fiebre 84%, tos seca 84%, disnea 56%, odinofagia 56%, coriza 32%, cefalea 24%, dolor torácico 24%, diarrea 16%, mialgia 8%, y fatiga 4%. Las comorbilidades se hallaron en el 16% (hipertensión arterial, diabetes mellitus tipo 2, cáncer, asma e hipotiroidismo). Requirió hospitalización el 40% (10/25) de los casos, y sólo 8% (2/25) necesitó ser admitido a la Unidad de Cuidados Intensivos (UCI). No hubo ningún paciente fallecido. Conclusiones: Encontramos que la mayoría fueron casos importados o relacionados, no hubo diferencias en el sexo, mayor frecuencia entre la cuarta y quinta década de la vida, cuadro clínico característico (fiebre, tos y disnea), presencia de comorbilidades, menos de la mitad requirió hospitalización, hallazgos característicos en la TEM pulmonar y muy pocos requirieron ingresar a la unidad de cuidados intensivos.Objective: To present the clinical and epidemiological characteristics of patients with COVID-19 treated in a private hospital in Lima. Material and Methods: A descriptive, retrospective and cross-sectional study is &nbsp;shown. There were 25 cases attended from March 9 to March 27 this year, during the current pandemic, which were treated at the Emergency Service of the Clinic Delgado, Miraflores, Lima. All of them were positive for rRT-PCR testing for coronavirus, performed at the Instituto Nacional de Salud, Lima. Results: Imported cases, 24% or their first contacts, 48%. Twelve (48%) were male. The median age was 38 year-old (range: 11-67 year-old) for males and 44 year-old (range: 33-71 year-old) for women; and, a global median of 40 year-old (range: 11- 71 year-old). Clinical manifestations were: fever 84%, dry cough 84%, dyspnea 56%, odynophagia 56%, coryza 32%, headache 24%, chest pain 24%, diarrhea 16%, myalgia 8%, and fatigue 4%. Comorbidities were found in 16% (high blood pressure, diabetes mellitus type 2, cancer, asthma and hypothyroidism). Forty per cent of cases required hospitalization, and only 8% needed to be admitted to the Intensive Care Unit (ICU). There was no deceased patient. Conclusions: We found that imported and related cases were majority, there were no differences in sex, more frequency between the fourth and fifth decade of life, characteristic clinical picture was present (fever, cough and dyspnea), comorbidities were found, less than a half required hospitalization, characteristic findings in pulmonary TEM were found and very few required entry into the ICU

Jaskaakin Shipibo joi wishati

Manual de escritura que presenta una serie de orientaciones para redactar un texto en la lengua shipibo-konibo: organización de ideas, uso de los principales signos de puntuación y algunos aspectos de la reflexión gramatical

Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines

The field of tumor vaccination is currently undergoing a shift in focus, from individualized tailor-made vaccines to more generally applicable vaccine formulations. Although primarily predicated by financial and logistic considerations, stemming from a growing awareness that clinical development for wide-scale application can only be achieved through backing from major pharmaceutical companies, these new approaches are also supported by a growing knowledge of the intricacies and minutiae of antigen presentation and effector T-cell activation. Here, the development of whole-cell tumor and dendritic cell (DC)-based vaccines from an individualized autologous set-up to a more widely applicable allogeneic approach will be discussed as reflected by translational studies carried out over the past two decades at our laboratories and clinics in the vrije universiteit medical center (VUmc) in Amsterdam, The Netherlands

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field