Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results

Background: Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. Methods: We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. Results: After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). Conclusions: LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therap

DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

<p>Abstract</p> <p>Background</p> <p>The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics.</p> <p>Methods</p> <p>DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA) hydrolysis assay.</p> <p>Results</p> <p>While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin). In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692), or did not exist for gemcitabine.</p> <p>Conclusion</p> <p>The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.</p

The 2018 European heatwave led to stem dehydration but not to consistent growth reductions in forests

Heatwaves exert disproportionately strong and sometimes irreversible impacts on forest ecosystems. These impacts remain poorly understood at the tree and species level and across large spatial scales. Here, we investigate the effects of the record-breaking 2018 European heatwave on tree growth and tree water status using a collection of high-temporal resolution dendrometer data from 21 species across 53 sites. Relative to the two preceding years, annual stem growth was not consistently reduced by the 2018 heatwave but stems experienced twice the temporary shrinkage due to depletion of water reserves. Conifer species were less capable of rehydrating overnight than broadleaves across gradients of soil and atmospheric drought, suggesting less resilience toward transient stress. In particular, Norway spruce and Scots pine experienced extensive stem dehydration. Our high-resolution dendrometer network was suitable to disentangle the effects of a severe heatwave on tree growth and desiccation at large-spatial scales in situ, and provided insights on which species may be more vulnerable to climate extremes

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Epidemiology of severe sepsis

Validar a polipectomia por vídeo-endoscopia como método terapêutico para pacientes com esterilidade, com sangramento uterino anormal e assintomáticas com pólipos endometriais. Pacientes e Métodos:Trabalho analítico e retrospectivo, cujos dados foram obtidos através de consultas aos prontuários de pacientes já submetidas a histeroscopias diagnósticas e cirúrgicas, no Setor de Endoscopia Ginecológica da Disciplina de Ginecologia da Faculdade de Medicina de Botucatu (UNESP) e da Clínica de Ginecologia Dr. Feres Abrão de Marília, atendidas entre o período de 2004 a 2005. Foram estudadas 208 mulheres submetidas ao exame histeroscópico com diagnóstico de pólipo endometrial. As pacientes foram distribuídas em 3 grupos, assim denominados: Grupo I (n=54), pacientes com queixa de esterilidade, Grupo II (n=59), pacientes com queixa de sangramento uterino anormal, Grupo III (n=95), pacientes assintomáticas com ultrassom vaginal anormal. Resultados: Pacientes do grupo I (Esterilidade), a faixa etária situou-se com maior incidência entre 31 e 35 anos, o peso situou-se entre 66,0 e 70,0 kg, o IMC de 20-25 (normal) em 50% dos casos, predominou a raça branca em 88,88%, não fumantes em 98,10%, hipertensão arterial em 1,85%, gestação 0 (G0) em 77,77%, associação de pólipo cervical e endometrial em 40%. A localização dos pólipos endometriais foi em 61,10% na parede anterior e posterior do útero. A biópsia orientada encontrou 11,11% de pólipos endometriais, sendo 100% benignos e o anátomo patológico, após polipectomia, encontrou 98,14% de pólipo endometriais benignos e pólipos endometriais com atipias em 1,85%. A esterilidade (1ª) ocorreu em 77,77% e secundária (2ª) em 33,33%, a gravidez ocorreu em 31,4% das pacientes no primeiro ano após a polipectomia e o ultrassom vaginal apresentou normalidade em 24% dos casos...To evaluate polypectomy by video-endoscopy as a method of treating patients with abnormal uterine bleeding and asymptomatic endometrial polyps. Patients and Methods: Retrospective analysis of data obtained from medical records of patients who had already undergone diagnostic and surgical endoscopies at The Gynaecology Discipline of Botucatu Medical School (UNESP), Botucatu, and The Dr. Feres Abrão Gynaecology Clinic, Marilia, SP, Brazil in 2004 and 2005. We studied 208 women submitted to hysteroscopy exam with a diagnosis of endometrial polyp. They were distributed into three groups: Group I (n=54) sterility; Group II (n=59) abnormal uterine bleeding; and Group III (n=95) asymptomatic with abnormal vaginal ultrasound. Results: In Group I (sterility) the most common age group was 31-35 years and weight between 66.0 and 70.0kg; 50% had BMI of 20-25 (normal), 88.88% were white, 98.10% were non-smokers, and 1.85% had arterial hypertension. Number of gestations was zero (G0) in 77.77%, 40% had associated cervical and endometrial polyps. In 61.10% of cases endometrial polyps were on the anterior and posterior uterine walls; guided biopsy found 11.11% of endometrial polyps which were all benign, and after polypectomy, anatomic pathology found benign polyps in 98.14% and atypical polyps in 1.85%. Primary sterility occurred in 77.77% and secondary in 33.33%, pregnancy in the first year after polypectomy occurred in 31.4%, and ultrasound was normal in 24% of cases. In Group II (abnormal uterine bleeding) the most common age group was 41-45 years and weight between 66.0 and 70.0kg; 49.15% had BMI 26-30 (overweight), 88.19% were white, 91.52% were non-smokers, and 10.16% had systemic arterial hypertension...(Complete abstract click electronic access below