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Background: The renin-angiotensin system is known to maintain blood pressure and body fluids. However, it has been found to consist of at least two major constituents, the classic and the alternative pathway, balancing and supporting each other's signalling in a very intricate way. Current research has shown that the renin-angiotensin system is involved in a broad range of biological processes and diseases, such as cancer and infectious diseases., Methods and Results: We conducted a literature review on the interaction of the renin-angiotensin system and prostate cancer and explored the research on the possible impact of the SARS-CoV-2 virus in this context. This review provides an update on contemporary knowledge into the alternative renin-angiotensin system, its role in cancer, specifically prostate cancer, and the implications of the current COVID-19 pandemic on cancer and cancer care., Conclusion: In this work, we aim to demonstrate how shifting the RAS signalling pathway from the classic to the alternative axis seems to be a viable option in supporting treatment of specific cancers and at the same time demonstrating beneficial properties in supportive care. It however seems to be the case that the infection with SARS-CoV-2 and subsequent impairment of the renin-angiotensin-system could exhibit serious deleterious long-term effects even in oncology., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Following health agencies warning, the use of animal origin supplements should be avoided in biological products proposed as therapy in humans. Platelet lysate and several other growth factors sources are alternatives to replace fetal calf serum, the current gold standard in clinical-grade cell culture. However, the platelet supplement's content lacks data due to different production methods. The principle behind these products relays on the lysis of platelets that release several proteins, some of which are contained in heterogeneous granules and coordinate biological functions. This study aims to analyze the composition and reproducibility of a platelet lysate produced with a standardized method, by describing several batches' protein and particle content using proteomics and dynamic light scattering. Proteomics data revealed a diversified protein content, with some related to essential cellular processes such as proliferation, morphogenesis, differentiation, biosynthesis, adhesion, and metabolism. It also detected proteins responsible for activation and binding of transforming growth factor beta, hepatocyte growth factor, and insulin-like growth factor. Total protein, biochemical, and growth factors quantitative data showed consistent and reproducible values across batches. Novel data on two major particle populations is presented, with high dispersion level at 231 ± 96 d.nm and at 30 ± 8 d.nm, possibly being an important way of protein trafficking through the cellular microenvironment. This experimental and descriptive analysis aims to support the content definition and quality criteria of a cell supplement for clinical applications., (© 2022 Wiley Periodicals LLC.)

NK cells have been seen as potential agents in adoptive immunotherapy for cancer. The main challenge for the success of this approach is to obtain a great quantity of activated NK cells for adoptive transfer. The present study had aimed to evaluate the effect of a feeder layer of irradiated MSCs in the in vitro expansion of NK cells. MSCs were obtained from the bone marrow (BM) cells remaining in the bag and filter used in the transplantation of hematopoietic stem cells. NK cells were obtained from peripheral blood (PB) of healthy volunteers. NK expansion and activation were stimulated by culture with artificial antigen-presenting cells (aAPCs) and IL-2, in the presence or absence of BM-MSCs. NK cell proliferation, phenotypic expression and cytotoxic activity were evaluated. Both culture conditions showed high NK purity with predominance of NK CD56 bright CD16 + subset post expansion. However, cultures without the presence of MSCs showed higher NK proliferation, expression of activation markers (CD16 and NKG2D) and related cytotoxic activity. In this experimental study, the presence of a feeder layer of irradiated BM-MSCs interfered negatively in the expansion of PB-NKs, limiting their growth and activation. Further investigation is needed to understand the mechanisms of NK-MSC interaction and its implications.

Background: Hematopoietic stem cell transplantation is a curative treatment for many patients with hematological disorders. Donor-recipient genetic disparity, especially involving the human leukocyte antigen system is a critical factor for transplant outcome., Objective: To evaluate retrospectively donor characteristics and correlations with the occurrence of acute and chronic graft-versus-host disease, disease-free survival and overall survival in a Brazilian population submitted to allogeneic hematopoietic stem cell transplantation between 1994 and 2012 in a single center., Results: Three hundred and forty-seven consecutive transplantations were included. Related transplants (81.2%) were significantly more common than unrelated transplants (18.7%); donor and recipient median ages were 34 (range: 1-61) and 33 (range: 3-65) years respectively with donor HLAs being matched for 333 (95.9%) patients. Donor gender, cytomegalovirus status and ABO incompatibility did not influence the five-year overall survival. In univariate analyses, overall survival was negatively influenced by the presence of acute graft-versus-host disease (33% vs. 47%, respectively; p -value = 0.04), unrelated transplant (41.5% vs. 50.9%, respectively; p -value = 0.045) and donors aged over 40 years (41% vs. 52%, respectively; p -value = 0.03). Older donors were associated with a higher rate of acute (52% vs. 65.8%; p -value = 0.03) and chronic graft-versus-host disease (60% vs. 43%, respectively; p -value = 0.015). In multivariate analyses, acute graft-versus-host disease [relative risk (RR): 1.8; 95% confidence interval (CI): 1.1-29; p -value = 0.008] and older donors (RR: 1.6; 95% CI 1.11-2.24; p -value = 0.013) were associated with higher transplant-related mortality., Conclusions: In transplant patients, to have a donor older than 40 years of age seems to significantly increase the incidence of acute and chronic graft-versus-host disease and transplant-related mortality with no impact on disease-free survival and overall survival. In spite of the rather small cohort of patients, these findings are similar to what is described in the literature suggesting that a younger donor should be chosen whenever possible.

Mesenchymal stem cells (MSC) are considered multipotent stromal, non-hematopoietic cells with properties of self-renovation and differentiation. Optimal conditions for culture of MSC have been under investigation. The oxygen tension used for cultivation has been studied and appears to play an important role in biological behavior of mesenchymal cells. The aim is characterize MSC in hypoxia and normoxia conditions comparing their morphological and functional characteristics. Bone marrow-derived mesenchymal stem cells obtained from 15 healthy donors and cultured. MSC obtained from each donor were separated into two cultivation conditions normoxia (21% O 2 ) and hypoxia (three donors at 1%, three donors at 2%, five donors at 3%, and four donors at 4% O 2 ) up to second passage. MSC were evaluated for proliferation, differentiation, immunophenotyping, size and cell complexity, oxidative stress, mitochondrial activity, and autophagy. Culture conditions applied did not seem to affect immunophenotypic features and cellular plasticity. However, cells subjected to hypoxia showed smaller size and greater cellular complexity, besides lower proliferation (P < 0.002). Furthermore, cells cultured in low O 2 tension had lower mitochondrial activity (P < 0.03) and a reduced tendency to autophagy, although oxidative stress did not vary among groups (P < 0.39). Oxygen tension seems to be a key regulator of cellular adaptation in vitro, and metabolic effects underlying this variable remain undescribed. Heterogeneity or even lack of results on the impact of oxygen concentration used for expanding MSC highlights the need for further research, in order to optimize conditions of cultivation and expansion and achieve greater safety and therapeutic efficacy. J. Cell. Biochem. 118: 3072-3079, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objectives: Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility., Methods: We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37)., Results: Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was <5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%)., Conclusion: Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

Objective: To translate the original English version of the Profile of Chronic Pain: Screen (PCP:S) into Brazilian Portuguese and examine basic psychometric properties of the translated version. We investigated ceiling and floor effects, internal consistency, factor structure, convergent validity, and the ability of the Brazilian PCP:S (B-PCP:S) to discriminate persons with pain who were either employed or not working, or in treatment or not in treatment., Methods: The Brazilian Portuguese version of the Profile of Chronic Pain: Screen (B-PCP:S) was administered to a sample of 414 adults (men = 67). Pain catastrophizing was also assessed. Subsamples with special conditions (working despite pain [N = 116] vs not working due to pain [N = 122], and not receiving treatment for pain [N = 119] vs receiving treatment [N = 119]) were identified to investigate the discriminative properties of B-PCP:S., Results: For the B-PCP:S, Cronbach's α values were 0.76 (severity), 0.88 (interference), and 0.87 (emotional burden). Confirmatory factor analysis supported the original, English language three-factor structure, with the comparative fit index = 0.93, root mean square error of approximation = 0.075, and normed fit index = 0.93. Significant correlations were found between pain intensity, pain interference, and emotional burden, and a criterion measure of catastrophizing (correlation coefficients ranged from 0.48 to 0.66, P < 0.01). B-PCP:S scores (severity, interference, and emotional burden) were higher in subjects under a doctor's care for pain and in those not working due to pain., Conclusion: This B-PCP:S version was found to be a reliable instrument, with basic evidence of validity for the evaluation of pain severity, interference, and emotional burden in Brazilian Portuguese adults. The profile of B-PCP:S scores was similar to that observed in the original version., (Wiley Periodicals, Inc.)

Objective: Catastrophizing is a maladaptive response to pain and is one of the factors that contribute to the chronicity of some pain syndromes. The Pain Catastrophizing Scale (PCS) assists both treatment planning and outcome assessment. Its use is limited in Portuguese-speaking countries because of the lack of a validated translated version. We conducted the validation of the Brazilian Portuguese (BP)-PCS and explored its psychometric properties. This study reports the internal consistency, factor structure, and its capability to discriminate pain reported by patients with specific chronic pain conditions., Methods: Three hundred eighty-four patients, 317 women (82.55%), aged 18-79 years with chronic nonmalignant pain attending an outpatient multidisciplinary pain center participated in this cross-sectional study. The instruments were the BP-PCS, pain intensity, pain interference in functional capacity, and a sociodemographic questionnaire. One subsample with chronic tensional headache (CTH) according to the criteria of the International Headache Society (N = 19), and another with a diagnosis of fibromyalgia according to the American College of Rheumatology criteria (N = 50) were selected to assess the discriminative properties of BP-PCS., Results: We observed good internal consistency (Cronbach's α values of 0.91 for the total BP-PCS, and 0.93 [helplessness], 0.88 [magnification], and 0.86 [rumination] for the respective subdomains). The item-total correlation coefficients ranged from 0.91 to 0.94. Confirmatory factor analysis (CFA) supported the three factors structure, with the comparative fit index = 0.98, root mean square error of approximation = 0.09, and normed fit index = 0.98. Significant correlations were found for pain intensity, pain interference, and patient's mood (correlation coefficients ranged from 0.48 to 0.66, P < 0.01). No significant gender difference was observed for BP-PCS scores. When comparing scores of BP-PCS scale and subscales between the selected control group (patients with pain scores on visual analog scale equal or lower than 40 mm in the most part of the day in the last 6 months) and patients with fibromyalgia or CTH, we observed lower scores for the former group., Conclusion: Our findings support the validity and reliability of the BP-PCS. The scale showed satisfactory psychometric properties. CFA provides support for the three-factor structure reported in previous studies. This factor structure presented good discriminative properties to identify catastrophizers who present with mild chronic pain, fibromyalgia, and CTH. The BP-PCS is a valuable tool for use in scientific studies and in the clinical setting in patients with chronic pain in Brazilian Portuguese-speaking countries., (Wiley Periodicals, Inc.)

The radiosynthesis of 3-(4-[(18)F]fluorophenyl)-2-(4-methylsulfonylphenyl)-1H-indole [(18)F]-3 as potential PET radiotracer for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo is described. [(18)F]-3 was prepared by McMurry cyclization of a (18)F-labeled intermediate with low valent titanium and zinc via a two-step procedure in a remote controlled synthesizer unit including HPLC purification and solid phase extraction. In this way [(18)F]-3 was synthesized in 80 min synthesis time in 10% total decay corrected yield from [(18)F]fluoride in radiochemical purity >98% and a specific activity of 74-91 GBq/μmol (EOS). [(18)F]-3 was evaluated in vitro using pro-inflammatory stimulated THP-1 and COX-2 expressing tumor cell lines (FaDu, A2058, HT-29), where the radiotracer uptake was shown to be consistent with up regulated COX-2 expression. The stability of [(18)F]-3 was determined by incubation in rat whole blood and plasma in vitro and by metabolite analysis of arterial blood samples in vivo, showing with 75% of original compound after 60 min an acceptable high metabolic stability. However, no substantial tumor accumulation of [(18)F]-3 could be observed by dynamic small animal PET studies on HT-29 tumor-bearing mice in vivo. This may be due to the only moderate COX-1/COX-2 selectivity of 3 as demonstrated by both cellular and enzymatic cyclooxygenase inhibition assay in vitro. Nevertheless, the new approach first using McMurry cyclization in (18)F-chemistry gives access to (18)F-labeled diarylsubstituted heterocycles that hold promise as radiolabeled COX-2 inhibitors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Benzodiazepines has been largely used to control anxiety and other clinical pictures since it began to be traded in the 60's. In recent years, many studies have shown that they are used indiscriminately, contributing to increase associated morbidity, and to search for other more accessible tranquilizers. PURPOSE--To estimate the prevalence of benzoadiazepine and over-the-counter tranquilizers use in adults living in Porto Alergre-RS, Brazil. METHODS--480 inhabitants of Porto Alegre, aged 18 or older, selected through a random cluster sampling procedure (sectors of the Brazilian Census), were interviewed in their homes during June, 1991. RESULTS--The prevalence for BDZ use during life, in the past year and in the past month was, respectively, 46.7%, 21.3% and 13.11%. Prevalence was significantly higher among women and widowers or divorced. The majority of those who used BDZ during the past month did so at least 2 or 3 days per week. More than 40% reported frequent over-the-counter substances use to "tranquilize", with a 28.8% prevalence for past month use. CONCLUSION--Chemical substance use to alleviate anxiety and other symptoms is generally spread. Legislation, not always respected, has been insufficient to discipline its use. Understanding the complexity of reasons for the situation to be unchanged is needed. Also necessary is the investment in education on adequate use of BDZ, both for physicians and population, and the search for legal measures that should be more efficient.