Role of the 5-HT1A receptors in the effect of Galanin(1-15) on Fluoxetine-mediated action in the forced swimming test

Galanin N-terminal fragment (1-15) [GAL(1-15)] modulates the antidepressant effects induced by the 5-HT1A receptor (5-HT1AR) agonist in the forced swimming test (FST) and the binding characteristics and mRNA levels of 5-HT1AR in the dorsal hippocampus and dorsal raphe (DR). Recently, we observed that GAL(1-15) enhanced the antidepressant-like effects induced by Fluoxetine (FLX) in the FST. In this work, we have studied whether the effects of GAL(1–15) on FLX action were mediated via 5-HT1AR, analyzing the effect of the 5-HT1AR antagonist WAY100635 in this effect and if the binding characteristics and mRNA levels of 5-HT1AR in the DR and dorsal hippocampus are modified by GAL(1-15)+FLX. Groups of rats (n=6-8) received three injections of sc FLX(10mg/kg) and 15 minutes before the FST a single icv injection of GAL(1-15) (1nmol) and 5HT1AR antagonist WAY100635(6nmol) icv alone or in combination. We also analyzed the effects of GAL(1-15)+FLX in the binding characteristics of the 5-HT1AR agonist [H3]-8-OH-DPAT and 5-HT1A mRNA levels in the DR, CA1 and Dentate Gyrus (DG). WAY100635 significantly blocked the reduction in immobility time (p<0.05), and the increase in swimming time (p<0.01) induced by GAL(1-15)+FLX in the FST. GAL(1-15)+FLX produced a significant increase in the 5HT1AR mRNA levels in CA1 (p<0.05) and DG (p<0.05). This effect was not observed in the DR. Moreover, GAL(1-15)+FLX produced a significant decrease in the Kd value (p<0.01) and in the Bmax value (p<0.05) of [3H]-8-OH-DPAT in the DG. These effects were not observed in the CA1 or in the DR. These results indicate that 5HT1AR participates in the GAL(1-15)/FLX interactions in the FST and the mechanism underlying affected the binding characteristics and the mRNA levels of 5-HT1AR specifically in the dorsal hippocampus. The heteroreceptor 5-HT1AR-GALR1-GALR2 located in the dorsal hippocampus may be the target for GAL(1-15). This work was supported by SAF2016-79008-P; PSI2013-44901-P.SAF2016-79008-P; PSI2013-44901-P. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Active surveillance for favorable-risk prostate cancer: Is there a greater psychological impact than previously thought? A systematic, mixed studies literature review.

OBJECTIVE: Active surveillance (AS) allows men with favorable-risk prostate cancer to avoid or postpone active treatment and hence spares potential adverse effects for a significant proportion of these patients. Active surveillance may create an additional emotional burden for these patients. The aim of the review was to determine the psychological impact of AS to inform future study in this area and to provide recommendations for clinical practice. METHODS: Studies were identified through database searching from inception to September 2015. Quantitative or qualitative noninterventional studies published in English that assessed the psychological impact of AS were included. The Mixed Methods Appraisal Tool was used to assess methodological quality. RESULTS: Twenty-three papers were included (20 quantitative and 3 qualitative). Quantitatively, the majority of patients do not report psychological difficulties; however, when appropriateness of study design is considered, the conclusion that AS has minimal impact on well-being may not be accurate. This is due to small sample sizes, inappropriately timed baseline, and inappropriate/lack of comparison groups. In addition, a mismatch in outcome was noted between the outcome of quantitative and qualitative studies in uncertainty, with qualitative studies indicating a greater psychological impact. CONCLUSIONS: Because of methodological concerns, many quantitative studies may not provide a true account of the burden of AS. Further mixed-methods studies are necessary to address the limitations highlighted and to provide clarity on the impact of AS. Practitioners should be aware that despite findings of previous reviews, patients may require additional emotional support

Galanin and neuropeptide y Y1 receptor agonist coinjection increases newborn cells proliferation on hippocampal dentate gyrus in rats

The hippocampus is a region in which neurogenesis persists throughout the lifespan in a wide variety of species including humans. Within the dentate gyrus of the hippocampus, the subgranular zone (SGZ) is maintained as a stem cell niche. We have previously shown that Galanin (GAL) interacts with Neuropeptide Y Y1 receptors (NPYY1R) in several regions of the central nervous system associated with mood and motivation. To examine the acute effects of GALR2/NPYY1R interactions on newborn cells proliferation we analyzed the effects of the intracerebroventricular (icv) of single injections with GAL and NPYY1 agonists or coadministered. Male Sprague-Dawley rats (n = 6-8 per group) were randomly assigned to the groups. Each group received i.c.v. injections of artificial Cerebro Spinal Fluid (aCSF), GAL or NPYY1R agonist [Leu31,Pro34]NPY alone or in combination. Intraperitoneal (ip) injections of exogenous cell DNA marker 5-bromo- 2-deoxyuridine (BrdU) 50mg/Kg were made at 2 and 4 hours after icv injections and 24 hours later rats were anesthetized, transcardially perfused and the brains collected for immunostaining to evaluate cell proliferation. Coadministration of GAL and NPYY1R agonist increased BrdU-labeled cells located in the SGZ (P<0,001) compared with aCSF, GAL and the NPYY1R-mediated hippocampal cell proliferation, These results will contribute to a better knowledge of the potential role of GAL and NPY family in mediating neurogenic actions and may give the basis for the therapeutic potential of targeting the GAL and NPY system in depressive disorders. Study supported by Proyecto Puente-Universidad de Málaga. Acknowledgements to Grupo Vithas.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Proyecto Puente-Universidad de Málaga

Definiendo patrones de ocupación mediante la monitorización de edificios existentes

Simulation programs are used to calculate the energy performance of buildings. However, numerous studies have shown a gap between calculated and actual thermal performance of buildings. One of the factors that have been identified as a source of uncertainty in building simulations is the occupancy of the building and occupants’ behaviour. These parameters are usually defined based on standards or assumed conditions. Thus, this research focuses on the occupants’ presence and behaviour in residential buildings. This paper presents an investigation on energy demand via dynamic building simulations and monitoring campaigns. The values obtained from the monitoring campaign were used as input data into the thermal simulation program and a comparison between normative and actual occupancy patterns was performed based on an occupied dwelling in Madrid, Spain.Para determinar el comportamiento energético de los edificios los programas de simulación dinámica son utilizados como métodos de cálculo. Sin embargo, numerosos estudios han mostrado que existen diferencias notables entre el comportamiento esperado y real de los edificios. Uno de los factores identificados como fuente de incertidumbre en la simulación de edificios es la ocupación y el comportamiento de los usuarios. Estos parámetros son definidos habitualmente con estándares que no reflejan la realidad de los ocupantes. En este artículo, se presenta una investigación sobre la influencia del comportamiento y la presencia de los usuarios de edificios residenciales en la demanda de energía. Para ello se generan modelos de simulación energética cuyos valores de entrada están ajustados con datos monitorizados de edificios reales. El estudio se realiza en dos casos de estudio ubicados en Madrid, España

Adubação fosfatada e intervalo de colheita no potencial energético do resíduo da colheita da erva-mate.

O trabalho objetivou avaliar o potencial energético e o efeito da adubação fosfatada e intervalos de colheita em propriedades físicas e químicas do resíduo da colheita da erva-mate e do briquete produzido com esse. Os resíduos foram obtidos em ervais que receberam doses de 0 e 320 kg ha-1 de P 2O5, com colheitas aos 12, 18 e 24 meses. Nesses resíduos e nos briquetes (produzidos a partir da fragmentação e compactação dos resíduos) avaliaram-se as propriedades físicas e químicas. O resíduo obtido de colheita com maiores intervalos apresentou maior densidade básica e poder calorífico superior. A colheita de 18 meses gerou resíduos para produção de briquetes com maior densidade energética. Conclui-se que o resíduo da colheita da erva-mate pode ser utilizado como fonte energética e que os briquetes produzidos com este resíduo apresentam propriedades energéticas adequadas, bem como, a adubação fosfatada não afeta o poder calorífico do resíduo da erva-mate

hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor for immunotherapy of uterine serous papillary carcinoma

BACKGROUND: Uterine serous papillary adenocarcinoma (USPC) is a highly aggressive variant of endometrial cancer. Human immunoconjugate molecule (hI-con1) is an antibody-like molecule targeted against tissue factor (TF), composed of two human Factor VII (fVII) as the targeting domain, fused to human immunoglobulin (Ig) G1 Fc as an effector domain. We evaluated hI-con1 potential activity against primary chemotherapy-resistant USPC cell lines expressing different levels of TF. METHODS: A total of 16 formalin-fixed, paraffin-embedded USPC samples were evaluated by immunohistochemistry (IHC) for TF expression. Six primary USPC cell lines, half of which overexpress the epidermal growth factor type II (HER2/neu) receptor at 3\ufe levels, were assessed by flow cytometry and real-time PCR for TF expression. Sensitivity to hI-con1-dependent cell-mediated cytotoxicity (IDCC) was evaluated in 5-hour-chromium release assays. Finally, to investigate the effect of interleukin-2 (IL-2) on IDCC, 5-h 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50\u2013100 IU ml 1). RESULTS: Cytoplasmic and/or membrane TF expression was observed in all 16 (100%) USPC samples tested by IHC, but not in normal endometrium. High expression of TF was found in 50% (three out of six) of the USPC cell lines tested by real-time PCR and flow cytometry when compared with normal endometrial cells (NECs; Po0.001). Uterine serous papillary adenocarcinoma cell lines overexpressing TF, regardless of their high or low HER2/neu expression, were highly sensitive to IDCC (mean killing\ub1s.d., 65.6\ub13.7%, range 57.5\u201377.0%, Po0.001), although negligible cytotoxicity against USPC was seen in the absence of hI-con1 or in the presence of Rituximab control antibody. The addition of low doses of IL-2 further increased the cytotoxic effect induced by hI-con1 against chemotherapy-resistant USPC. CONCLUSION: hI-con1 induces strong cytotoxicity against primary chemotherapy-resistant USPC cell lines overexpressing TF. The hI-con1 may represent a novel therapeutic agent for the treatment of patients harbouring advanced, recurrent and/or metastatic USPC refractory to standard treatment modalities

Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer

BACKGROUND: Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients. METHODS: SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR, immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied. RESULTS: SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by RT\u2013PCR\ubc162 vs 2.21; P\ubc0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (mgml 1) had a median (95% CIs) of 6.0 (4.0\u20138.9) in normal healthy females and 6.0 (4.2\u20138.1) in patients with benign disease (P\ubc0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2\u201356.2), significantly higher than those in the healthy group (P\ubc0.0005) and benign group (P\ubc0.0006). Receiver operating characteristics (ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837 (P\ubc0.0024). CONCLUSION: SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy