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1.
Exp Neurol ; : 113245, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32067950

RESUMO

BACKGROUND AND PURPOSE: N,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 receptor (Sig-1R) with documented in vitro cytoprotective properties against hypoxia. Our aim was to demonstrate the in vivo neuroprotective effect of DMT following ischemia-reperfusion injury in the rat brain. METHODS: Transient middle cerebral occlusion (MCAO) was induced for 60 min in male Wistar rats using the filament occlusion model under general anaesthesia. Before the removal of the filament the treatment group (n = 10) received an intra-peritoneal (IP) bolus of 1 mg/kg-body weight (bw) DMT dissolved in 1 ml 7% ethanol/saline vehicle, followed by a maintenance dose of 2 mg/Kg-bw/h delivered over 24 h via osmotic minipumps. Controls (n = 10) received a vehicle bolus only. A third group (n = 10) received a Sig-1R antagonist (BD1063, 1 mg/kg-bw bolus +2 mg/kg-bw/h maintenance) in parallel with the DMT. Lesion volume was measured by MRI 24 h following the MCAO. Shortly after imaging the animals were terminated, and the native brains and sera were removed. Four rats were perfusion fixed. Functional recovery was studied in two separate group of pre-trained animals (n = 8-8) using the staircase method for 30 days. The expression levels of proteins involved in apoptosis, neuroplasticity and inflammatory regulation were assessed by real-time qPCR and ELISA. RESULTS: DMT treated rats were characterized by lower ischemic lesion volume (p = .0373), and better functional recovery (p = .0084) compared to the controls. Sig-1R was expressed both in neurons and in microglia in the peri-infarct cortex, and the DMT induced change in the lesion volume was hindered by BD1063. Lower APAF1 expression (mRNA and protein) and higher BNDF levels were documented on DTM, while decreased TNF-α, IL1-ß, IL-6 and increased IL-10 expressions indicated the compound's anti-inflammatory potential. CONCLUSION: Our results indicate a Sig-1R dependent reduction of the ischemic brain injury following exogenous DMT administration in rats, presumably through a combined anti-apoptotic, pro-neurotrophic and anti-inflammatory treatment effect.

2.
Rev Neurosci ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32007948

RESUMO

The microbiota and microbiome and disruption of the gut-brain axis were linked to various metabolic, immunological, physiological, neurodevelopmental, and neuropsychiatric diseases. After a brief review of the relevant literature, we present our hypothesis that intestinal serotonin, produced by intestinal enterochromaffin cells, picked up and stored by circulating platelets, participates and has an important role in the regulation of membrane permeability in the intestine, brain, and other organs. In addition, intestinal serotonin may act as a hormone-like continuous regulatory signal for the whole body, including the brain. This regulatory signal function is mediated by platelets and is primarily dependent on and reflects the intestine's actual health condition. This hypothesis may partially explain why gut dysbiosis could be linked to various human pathological conditions as well as neurodevelopmental and neuropsychiatric disorders.

3.
Eur J Sport Sci ; : 1-26, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023170

RESUMO

Research over the past 15 years on the placebo effect has substantiated its contribution to the efficacy of established treatments for a range of clinical conditions and identified its underlying mechanisms. There is also evidence that placebo effects contribute to the performance benefits of many ergogenic aids, and that performance can worsen when dummy treatments are associated with expectations of a harmful outcome (i.e., the nocebo effect). Unfortunately, the bulk of sport research involving placebos and nocebos continues to be hampered by outdated definitions and conceptualizations of the placebo effect and its mechanisms. This has implications not only for research but also application, as nearly 50% of athletes report experiencing a beneficial placebo effect, and a similar proportion of coaches report providing placebos to their athletes. The objective of this paper is to attempt to stimulate research by presenting updated definitions of the placebo and nocebo effects in the context of sport, describing their major mechanisms and, highlighting the importance of the psychosocial setting in the sport setting on placebo effects.

5.
World J Microbiol Biotechnol ; 36(2): 29, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32016527

RESUMO

Short-chain halogenated aliphatic hydrocarbons (e.g. perchloroethene, trichloroethene) are among the most toxic environmental pollutants. Perchloroethene and trichloroethene can be dechlorinated to non-toxic ethene through reductive dechlorination by Dehalococcoides sp. Bioaugmentation, applying cultures containing organohalide-respiring microorganisms, is a possible technique to remediate sites contaminated with chlorinated ethenes. Application of site specific inocula is an efficient alternative solution. Our aim was to develop site specific dechlorinating microbial inocula by enriching microbial consortia from groundwater contaminated with trichloroethene using microcosm experiments containing clay mineral as solid phase. Our main goal was to develop fast and reliable method to produce large amount (100 L) of bioactive agent with anaerobic fermentation technology. Polyphasic approach has been applied to monitor the effectiveness of dechlorination during the transfer process from bench-scale (500 mL) to industrial-scale (100 L). Gas chromatography measurement and T-RFLP (Terminal Restriction Fragment Length Polymorphism) revealed that the serial subculture of the enrichments shortened the time-course of the complete dechlorination of trichloroethene to ethene and altered the composition of bacterial communities. Complete dechlorination was observed in enrichments with significant abundance of Dehalococcoides sp. cultivated at 8 °C. Consortia incubated in fermenters at 18 °C accelerated the conversion of TCE to ethene by 7-14 days. Members of the enrichments belong to the phyla Bacteroidetes, Chloroflexi, Proteobacteria and Firmicutes. According to the operational taxonomic units, main differences between the composition of the enrichment incubated at 8 °C and 18 °C occurred with relative abundance of acetogenic and fermentative species. In addition to the temperature, the site-specific origin of the microbial communities and the solid phase applied during the fermentation technique contributed to the development of a unique microbial composition.


Assuntos
Anaerobiose/fisiologia , Bactérias/metabolismo , Biodegradação Ambiental , Argila/química , Microbiota/fisiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteroidetes/genética , Bacteroidetes/metabolismo , Chloroflexi/genética , Chloroflexi/metabolismo , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Fermentação , Firmicutes/genética , Firmicutes/metabolismo , Geobacter/genética , Geobacter/metabolismo , Água Subterrânea/microbiologia , Consórcios Microbianos , Polimorfismo de Fragmento de Restrição , Proteobactérias/genética , Proteobactérias/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/isolamento & purificação , Tricloroetileno/química , Microbiologia da Água , Poluentes Químicos da Água/metabolismo
6.
J Transl Med ; 18(1): 36, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31973719

RESUMO

BACKGROUND: Recently, involvement of IL-19, IL-20 and IL-24 has been reported in inflammatory diseases associated with tissue remodeling. However, their impact on the pathomechanism of coeliac disease (CD) is still completely unknown. METHODS: Expression of IL19, IL20 and IL24 was measured by real-time RT-PCR, protein amount of IL-24, α smooth muscle actin (α-SMA) and fibronectin (FN) was determined by Western-blot analysis in the duodenal biopsies of therapy naive children with CD and controls. Localization of IL-24 and IL-20RB was investigated by immunofluorescent staining in the duodenal mucosa. Effect of recombinant IL-1ß, TNF-α, TGF-ß and IL-17 treatment on the expression of IL19, IL20, IL24 and their receptors was investigated by real-time RT-PCR in small intestinal epithelial cells (FHs74Int), in primary duodenal myofibroblasts (pdMFs) and in peripheral blood mononuclear cells (PBMCs). Effect of IL-24 on H2O2 treated FHs74Int cells and on pdMFs was measured by MTT, LDH, Annexin V assays, real-time RT-PCR and by fluorescent microscopy. RESULTS: We found increased level of IL-24 (3.3×, p < 0.05), α-SMA (2.4×, p < 0.05) and FN (2.3×, p < 0.05) in the duodenal mucosa and increased expression of IL19 (3.6×, p < 0.05) and IL24 (5.2×, p < 0.05) in the PBMCs of children with CD compared to that of controls. IL-1ß was a strong inducer of IL24 expression of FHs74Int cells (9.9×, p < 0.05), pdMFs (552.9×, p < 0.05) or PBMCs (17.2×, p < 0.05), as well. IL-24 treatment reduced the number of apoptotic cells (0.5×, p < 0.05) and decreased the expression of inflammatory factors, including IL1A, IL6 and TNF of H2O2-treated FHs74Int cells. IL-24 decreased the proliferation (0.6×, p < 0.05) of PDGF-B treated pdMFs. Moreover, IL-24 treatment altered the morphology of pdMFs by influencing the size of the angles between stress fibers and the longitudinal axis of the cells (2.0×, p < 0.05) and the expression of cytoskeletal components, including ACTA2, ACTB, VIM, SNAI1 and SNAI2. CONCLUSION: Our results suggest that IL-24 plays a significant role in the maintenance of duodenal mucosal integrity in CD.

7.
Pediatr Res ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785594

RESUMO

BACKGROUND: There is an association between hypocapnia and adverse neurodevelopmental outcome in infants with neonatal encephalopathy (NE). Our aim was to test the safety and feasibility of 5% CO2 and 95% air inhalation to correct hypocapnia in mechanically ventilated infants with NE undergoing therapeutic hypothermia. METHODS: Ten infants were assigned to this open-label, single-center trial. The gas mixture of 5% CO2 and 95% air was administered through patient circuits if the temperature-corrected PCO2 ≤40 mm Hg. The CO2 inhalation was continued for 12 h or was stopped earlier if the base deficit (BD) level decreased <5 mmol/L. Follow-up was performed using Bayley Scales of Infant Development II. RESULTS: The patients spent a median 95.1% (range 44.6-98.5%) of time in the desired PCO2 range (40-60 mm Hg) during the inhalation. All PCO2 values were >40 mm Hg, the lower value of the target range. Regression modeling revealed that BD and lactate had a tendency to decrease during the intervention (by 0.61 and 0.55 mmol/L/h, respectively), whereas pH remained stable. The rate of moderate disabilities and normal outcome was 50%. CONCLUSIONS: Our results suggest that inhaled 5% CO2 administration is a feasible and safe intervention for correcting hypocapnia.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31822925

RESUMO

RATIONALE: 5-methoxy-N,N-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-N,N-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. However, scientific knowledge on the effects of 5-methoxy-N,N-dimethyltryptamine in humans is scarce. OBJECTIVES: The first objective was to assess the effects of inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine on neuroendocrine markers. The second objective was to assess effects of the substance on affect and mindfulness. In addition, we assessed whether ratings of subjective measures were associated with changes in stress biomarkers (i.e., cortisol) and immune response (i.e., IL-6, CRP, IL-1ß), as well as the acute psychedelic experience. METHODS: Assessments (baseline, immediately post-session, and 7-day follow-up) were made in 11 participants. Salivary samples were collected at baseline and post-session and analyzed by high-sensitivity enzyme-linked immunosorbent assay (ELISA). RESULTS: 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately post-session. These changes were not correlated to ratings of mental health or the psychedelic experience. Relative to baseline, ratings of non-judgment significantly increased, and ratings of depression decreased immediately post-session and at follow-up. Ratings of anxiety and stress decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with ratings of affect and positively with ratings of non-judgment. CONCLUSION: Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine produced significant changes in inflammatory markers, improved affect, and non-judgment in volunteers. Future research should examine the effect of 5-methoxy-N,N-dimethyltryptamineamine with healthy volunteers in a controlled laboratory setting.

9.
Pediatr Nephrol ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31781959

RESUMO

The contribution of high sodium intake to hypertension and to the severity of immune-mediated diseases is still being heatedly debated in medical literature and in the lay media. This review aims to demonstrate two conflicting views on the topic, with the first part citing the detrimental effects of excessive salt consumption. Sodium plays a central role in volume and blood pressure homeostasis, and the positive correlation between sodium intake and blood pressure has been extensively researched. Despite the fact that the average of global daily salt consumption exceeds recommendations of international associations, health damage from excessive salt intake is still controversial. Individual differences in salt sensitivity are in great part attributed to this contradiction. Patients suffering from certain diseases as well as other vulnerable groups-either minors or individuals of full age-exhibit more pronounced blood pressure reduction when consuming a low-sodium diet. Furthermore, findings from the last two decades give insight into the concept of extrarenal sodium storage; however, the long-term consequences of this phenomenon are lesser known. Evidence of the relationship between sodium and autoimmune diseases are cited in the review, too. Nevertheless, further clinical trials are needed to clarify their interplay. In conclusion, for salt-sensitive risk groups in the population, even stricter limits of sodium consumption should be set than for young, healthy individuals. Therefore, the question raised in the title should be rephrased as follows: "how much salt is harmful" and "for whom is elevated salt intake harmful?"

10.
Orphanet J Rare Dis ; 14(1): 247, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703608

RESUMO

BACKGROUND: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. RESULTS: One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. CONCLUSIONS: In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients.

11.
J Chem Phys ; 151(15): 154115, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640370

RESUMO

In single-molecule force spectroscopy experiments, a biomolecule is attached to a force probe via polymer linkers and the total extension of the molecule plus apparatus is monitored as a function of time. In a typical unfolding experiment at constant force, the total extension jumps between two values that correspond to the folded and unfolded states of the molecule. For several biomolecular systems, the committor, which is the probability to fold starting from a given extension, has been used to extract the molecular activation barrier (a technique known as "committor inversion"). In this work, we study the influence of the force probe, which is much larger than the molecule being measured, on the activation barrier obtained by committor inversion. We use a two-dimensional framework in which the diffusion coefficient of the molecule and of the pulling device can differ. We systematically study the free energy profile along the total extension obtained from the committor by numerically solving the Onsager equation and using Brownian dynamics simulations. We analyze the dependence of the extracted barrier on the linker stiffness, molecular barrier height, and diffusion anisotropy and, thus, establish the range of validity of committor inversion. Along the way, we showcase the committor of 2-dimensional diffusive models and illustrate how it is affected by barrier asymmetry and diffusion anisotropy.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31592761

RESUMO

A new aerobic betaproteobacterium, strain SA-152T, was isolated from the water of a crater lake. 16S rRNA gene sequence analysis revealed that strain SA-152T belonged to the family Oxalobacteraceae (order Burkholderiales) and was phylogenetically related to Solimicrobium silvestre S20-91T with 97.09 % and to Herminiimonas arsenicoxydans ULPAs1T with 96.00 % 16S rRNA gene pairwise sequence similarity. Cells of strain SA-152T were rod-shaped, non-motile, oxidase-negative and catalase-positive. Its fatty acid profile was dominated by two fatty acids, C16 : 1 ω7c and C16 : 0, the major respiratory quinones were Q-8 and Q-7, and the main polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The G+C content of the genomic DNA of strain SA-152T was 48.3 mol%. The new bacterium can be distinguished from closely related genera Solimicrobium, Herminiimonas, Rugamonas and Undibacterium based on its non-motile and oxidase-negative cells. On the basis of the phenotypic, chemotaxonomic and genomic data, strain SA-152T is considered to represent a novel species of a new genus, for which the name Sapientia aquatica gen. nov., sp. nov. is proposed. The type strain of Sapientia aquatica is SA-152T (=DSM 29805T=NCAIM B.02613T).

13.
Eur J Sport Sci ; : 1-9, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31566508

RESUMO

The understanding of placebo and nocebo effects in psychological responses to exercise may be improved by measuring expectations. Despite availability of several validated expectation measures, we argue for using scales that take both positive and negative expectations for exercise-induced changes into account. A cross-sectional survey was used to collect information on positive and negative expectations pertaining to how exercise would affect 14 different outcomes related to psychological health (n = 966). Outcomes for which a majority of the sample (>50%) reported positive expectations for exercise-induced changes included: psychological well-being (75.3%), depression (74.3%), relaxation (74.2%), sleep quality (73.3%), stress (72.2%), anxiety (69.8%), energy (67.1%), and attention (60.2%). Outcomes for which a majority of the sample (>50%) reported a negative expectation for exercise-induced changes were muscle pain (66.3%), fatigue (57.3%), and joint pain (50.7%). Across all 14 outcomes, the percentage of participants with negative expectations for exercise-induced changes ranged from 5.9 to 66.3%. Elucidating the potential presence of placebo and nocebo effects through measurement of expectations may improve the understanding of variability in the direction and magnitude of exercise-related effects on psychological health. Although there were only 3 outcomes for which the majority of participants reported negative expectations, we found that negative expectations were present to some degree for all 14 outcomes. Thus, for researchers who wish to characterize expectations in studies of psychological responses to exercise, we recommend using measures that give equal consideration to positive and negative expectations.

14.
Eur J Sport Sci ; : 1-14, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31414966

RESUMO

The aim of this review was to determine the magnitude of the placebo and nocebo effect on sport performance. Articles published before March 2019 were located using Medline, Web of Science, PubMed, EBSCO, Science Direct, and Scopus. Studies that examined placebo and nocebo effects of an objective dependent variable on sports performance, which included a control or baseline condition, were included in the analysis. Studies were classified into two categories of ergogenic aids: (1) nutritional and (2) mechanical. Cohen's d effect sizes were calculated from 32 studies involving 1513 participants. Small to moderate placebo effects were found for both placebo (d = 0.36) and nocebo (d = 0.37) effects and when separated by nutritional (d = 0.35) and mechanical (d = 0.47) ergogenic aids. The pooled effect size revealed a small to moderate effect size across all studies (d = 0.38). Results suggest that placebo and nocebo effects can exert a small to moderate effect on sports performance.

15.
Pediatr Transplant ; 23(6): e13529, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31259462

RESUMO

Sleep-disordered breathing, a prevalent condition among adult renal transplant (RTx) recipients, has become an established independent risk factor of MetS, and furthermore, it might contribute to increased CV risk. Despite the proven correlations in adults, there is a lack of evidence for its significance in the pediatric RTx population. In this study, we aimed at assessing the prevalence and the clinical correlates of SDB in RTx children. Data of 13 patients (age [mean ± SD]: 14.2 ± 2.7 years) were analyzed. SDB was evaluated by PSG, as severity score OAHI was applied. Carbohydrate metabolism was characterized by OGTT, whereas CV status was studied by ABPM. Three composite end-points were calculated as sum of z-scores: daytime systolic and diastolic BP; nighttime systolic and diastolic BP; and glucose and insulin levels at 120 minutes. Eight patients (61.5%) were diagnosed with SDB of whom five patients (38.5%) had moderate or severe SDB. In linear regression analysis, OAHI during REM was associated with the CV variables (daytime BP P = 0.032, ß = 0.748; nighttime BP P = 0.041, ß = 0.715), and the correlations remained significant after adjustments for BMI. However, we did not confirm a significant association with the metabolic variables. The prevalence of SDB was high, and its severity during REM was a predictor of the BP suggesting that RTx children with SDB might be at risk of developing CV complications, especially HTN similarly to adults.

16.
J Pediatr ; 211: 13-19.e3, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31155392

RESUMO

OBJECTIVE: To investigate whether hydrocortisone supplementation increases blood pressure and decreases inotrope requirements compared with placebo in cooled, asphyxiated neonates with volume-resistant hypotension. STUDY DESIGN: A double-blind, randomized, placebo-controlled clinical trial was conducted in a Level III neonatal intensive care unit in 2016-2017. Thirty-five asphyxiated neonates with volume-resistant hypotension (defined as a mean arterial pressure [MAP] < gestational age in weeks) were randomly assigned to receive 0.5 mg/kg/6 hours of hydrocortisone or placebo in addition to standard dopamine treatment during hypothermia. RESULTS: More patients reached the target of at least 5-mm Hg increment of MAP in 2 hours after randomization in the hydrocortisone group, compared with the placebo group (94% vs 58%, P = .02, intention-to-treat analysis). The duration of cardiovascular support (P = .001) as well as cumulative (P < .001) and peak inotrope dosage (P < .001) were lower in the hydrocortisone group. In a per-protocol analysis, regression modeling predicted that a 4-mm Hg increase in MAP in response to hydrocortisone treatment was comparable with the effect of 15 µg/kg/min of dopamine in this patient population. Serum cortisol concentrations were low before randomization in both the hydrocortisone and placebo groups (median 3.5 and 3.3 µg/dL, P = .87; respectively), suggesting inappropriate adrenal function. Short-term clinical outcomes were similar in the 2 groups. CONCLUSIONS: Hydrocortisone administration was effective in raising the blood pressure and decreasing inotrope requirement in asphyxiated neonates with volume-resistant hypotension during hypothermia treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02700828.

17.
Eur J Sport Sci ; : 1-12, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31215360

RESUMO

Despite the apparent strength of scientific evidence suggesting that psychological benefits result from both acute and chronic exercise, concerns remain regarding the extent to which these benefits are explained by placebo effects. Addressing these concerns is methodologically and at times conceptually challenging. However, developments in the conceptualisation and study of placebo effects from the fields of psychology, neuroscience, pharmacology, and human performance offer guidance for advancing the understanding of placebo effects in psychological responses to exercise. In clinical trials, expectations can be measured and experimentally manipulated to better understand the influence of placebo effects on treatment responses. Further, compelling evidence has shown that the contribution of placebo effects and their underlying neurobiological mechanisms to treatment effects can be measured without administering a traditional placebo (e.g. inert substance) by leveraging psychological factors such as expectations and conditioning. Hence, the purpose of this focused review is to integrate lessons such as these with the current body of literature on placebo effects in psychological responses to exercise and provide recommendations for future research directions.

18.
J Genet ; 98(2)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31204695

RESUMO

It is now common knowledge-but also a misbelief-that in 1905 William Bateson coined the term 'genetics' for the first time in his letter to Adam Sedgwick. This important term was already formulated 81 years ago in a paper written by a sheepbreeding noble called Imre (Emmerich) Festetics, who still remains somewhat mysterious even today. The articles written by Festetics summarized the results of a series of lasting and elegant breeding experiments he had conducted on his own property. Selecting the best rams, Festetics had painstakingly crossed and backcrossed his best sheep to reach better wool quality. These experiments later turned out to reveal a better understanding of inheritance outlining genetics as a new branch of natural sciences.


Assuntos
Galinhas/genética , Genética/história , Ervilhas/genética , Ovinos/genética , Animais , Cruzamento , Genética Populacional , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , Humanos
19.
Diabetologia ; 62(8): 1501-1513, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31053872

RESUMO

AIMS/HYPOTHESIS: Diabetes is a worldwide epidemic linked with diverse diseases of the nervous system, including depression. A few studies suggested a connection between renin-angiotensin-aldosterone system blockers and reduced depressive symptoms, although underlying mechanisms are unclear. Here we investigated the antidepressant effect and the mechanisms of action of the angiotensin receptor 1 blocker (ARB) losartan in an experiential model of diabetes-associated depression. METHODS: Experimental diabetes was induced by streptozotocin in adult male Wistar rats. After 5 weeks of diabetes, rats were treated for 2 weeks with a non-pressor oral dose of losartan (20 mg/kg). In protocol 1, cerebrovascular perfusion and glial activation were evaluated by single-photon emission computed tomography-MRI and immunohistochemistry. In protocol 2, behaviour studies were performed (forced swim test and open field test). Hippocampal proinflammatory response and brain-derived neurotrophic factor (BDNF) signalling were also assessed. RESULTS: Here, we show that diabetic rats exhibit depression-like behaviour, which can be therapeutically reversed by losartan. This action of losartan occurs via changes in diabetes-induced neuroinflammatory responses rather than altered cerebral perfusion. We also show that as a part of its protective effect losartan restores BDNF production in astrocytes and facilitates BDNF-tropomyosin receptor kinase B-cAMP response element-binding protein signalling in the diabetic brain. CONCLUSIONS/INTERPRETATION: We identified a novel effect of losartan in the nervous system that may be implemented to alleviate symptoms of diabetes-associated depression. These findings explore a new therapeutic horizon for ARBs as possible antidepressants and suggest that BDNF could be a target of future drug development in diabetes-induced complications.

20.
Int J Syst Evol Microbiol ; 69(6): 1724-1730, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31038452

RESUMO

A Gram-stain-negative, aerobic, non-motile and coccus-shaped bacterium, designated strain FeSDHB5-19T, was isolated from a biofilm sample collected from a radioactive thermal spring (Budapest, Hungary), after exposure to 5 kGy gamma radiation. A polyphasic approach was used to study the taxonomic properties of strain FeSDHB5-19T, which had highest 16S rRNA gene sequence similarity to Deinococcus antarcticus G3-6-20T (96.5 %). The 16S rRNA gene sequence similarity to type strains of other Deinococcus species were 93.0 % or lower. The DNA G+C content of the draft genome sequence, consisting of 3.9 Mb, was 63.9 mol%. Strain FeSHDB5-19T was found to grow at temperatures of 10-32 °C (optimum, 28 °C) and pH 5-10 (pH 6.5-7.5) and tolerated up to 1.5 % NaCl (w/v) with optimum growth at 0-0.5 % NaCl. The predominant fatty acids (>10 %) were C16 : 0 and C16 : 1ω7c. The cell-wall peptidoglycan type was A3ß l-Orn-Gly1-2. The whole-cell sugars were glucose and low amounts of galactose. Strain FeSDHB5-19T possessed MK-8 as the predominant respiratory quinone, typical of the genus Deinococcus. The polar lipid profile contained unidentified phosphoglycolipids and unidentified glycolipids. The isolate was found to be highly resistant to gamma (D10<8 kGy) and UV (D10~800 J m-2) radiation. According to its genotypic, phenotypic and chemotaxonomic characteristics, strain FeSDHB5-19T represents a novel species in the genus Deinococcus, for which the name Deinococcusfonticola sp. nov. is proposed. The type strain is FeSDHB5-19T (=NCAIM B.02639T=DSM 106917T).


Assuntos
Deinococcus/classificação , Raios gama , Fontes Termais/microbiologia , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Deinococcus/isolamento & purificação , Ácidos Graxos/química , Glicolipídeos/química , Hungria , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
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