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1.
J Physiol ; 598(6): 1253-1270, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917868

RESUMO

KEY POINTS: Acute biliary pancreatitis is a significant clinical challenge as currently no specific pharmaceutical treatment exists. Intracellular Ca2+ overload, increased reactive oxygen species (ROS) production, mitochondrial damage and intra-acinar digestive enzyme activation caused by bile acids are hallmarks of acute biliary pancreatitis. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. We demonstrated that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2 O2 treatment and contributed to bile acid-induced extracellular Ca2+ influx in acinar cells, which promoted acinar cell necrosis in vitro and in vivo. These results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis. ABSTRACT: Acute biliary pancreatitis poses a significant clinical challenge as currently no specific pharmaceutical treatment exists. Disturbed intracellular Ca2+ signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra-acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca2+ overload is a promising therapeutic target. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2 O2 treatment. TRPM2 activity was found to contribute to bile acid-induced extracellular Ca2+ influx in acinar cells, but did not have the same effect in ductal cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells compared to isolated ducts, which can explain the difference between acinar and ductal cells. This activity promoted acinar cell necrosis in vitro independently from mitochondrial damage or mitochondrial fragmentation. In addition, bile-acid-induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein-induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.

2.
Fetal Diagn Ther ; 47(2): 91-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31167195

RESUMO

INTRODUCTION: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. MATERIALS AND METHODS: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. RESULTS: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. CONCLUSION: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.

3.
J Clin Monit Comput ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31555917

RESUMO

Video laryngoscopy (VL) is a well-established technique used in anaesthetising obese patients who present with higher risks of airway-related difficulties and desaturations due to shorter safe apnoea periods. However, VL has certain limitations and may fail. We present the Infrared Red Intubation System (IRRIS), a new technique facilitating glottis identification in severely obese patients undergoing anaesthesia for bariatric surgery. This single-centre, prospective trial assessed the efficacy of the IRRIS for VL tracheal intubation in 20 severely obese adult patients undergoing elective bariatric surgery under general anaesthesia. We assessed the ability of the IRRIS to differentiate the transilluminated glottis from the oesophagus and laryngeal folds and evaluated the ease of intubation. The average weight in the investigated patient cohort was 145 ± 29 kg, the suprasternal tissue thickness was 12 ± 4 mm. The median IQR [range] larynx recognition time was 10 [2-50] s, which was similar to that of lean patients. The degree of obesity correlated with the duration to achieve optimal laryngoscopic view and complete the intubation procedure. We achieved successful VL insertion on the first attempt in 13 of 20 cases (65%), and on the second attempt in 7 cases (35%), emphasising the increased probability of successful intubation on the first attempt. Tracheal intubation with the IRRIS lasted 50 [IQR 20-100] s. The lowest SpO2 during intubation was 98 [IQR 83-100] %. Addition of IRRIS to VL insertion facilitated the intubation of difficult airways in severely obese patients. IRRIS improves the visualization of the intubation pathway by selectively highlighting the airway entrance and shortens the time to successfully conclude the intubation procedure.

4.
Evol Appl ; 12(6): 1092-1095, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31293625

RESUMO

While obesity is widely recognized as a risk factor for cancer, survival among patients with cancer is often higher for obese than for lean individuals. Several hypotheses have been proposed to explain this "obesity paradox," but no consensus has yet emerged. Here, we propose a novel hypothesis to add to this emerging debate which suggests that lean healthy persons present conditions unfavorable to malignant transformation, due to powerful natural defenses, whereby only rare but aggressive neoplasms can emerge and develop. In contrast, obese persons present more favorable conditions for malignant transformation, because of several weight-associated factors and less efficient natural defenses, leading to a larger quantity of neoplasms comprising both nonaggressive and aggressive ones to regularly emerge and progress. If our hypothesis is correct, testing would require the consideration of the raw quantity, not the relative frequency, of aggressive cancers in obese patients compared with lean ones. We also discuss the possibility that in obese persons, nonaggressive malignancies may prevent the subsequent progression of aggressive cancers through negative competitive interactions between tumors.

5.
Anesth Analg ; 129(2): e62, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31313672
6.
Anesth Analg ; 129(4): e139-e140, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31348057
8.
Anesth Analg ; 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31136325
9.
J Sleep Res ; 28(3): e12721, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29961995

RESUMO

Fatigue in multiple sclerosis is a very common and cumbersome symptom, but its aetiology is poorly understood. Proteomics is increasingly implemented in multiple sclerosis research, but has not yet been used to study the neurobiological basis of fatigue in multiple sclerosis. To identify potential cerebrospinal fluid biomarkers of fatigue in multiple sclerosis, we collected cerebrospinal fluid of 20 patients with multiple sclerosis with fatigue (MS+), 20 patients with multiple sclerosis without fatigue (MS-), and 20 control subjects without multiple sclerosis and without fatigue (HC). We used a shotgun proteomics approach and label-free quantitative proteomics to analyse the protein content in cerebrospinal fluid. Selected proteins with differential abundance were further validated by immunoblotting. Out of 591 detected cerebrospinal fluid proteins, the abundance of nine proteins differed between the three groups, and seven additional proteins differed between MS+ and MS- patients. Using immunoblot or slot-blot techniques, we confirmed decreased levels of protein kinase C-binding protein NELL2, neural cell adhesion molecule L1-like protein, and reelin in MS+ patients. In conclusion, cerebrospinal fluid proteomics may provide insight into the neurobiological basis of fatigue in multiple sclerosis. The proteins identified to be decreased in MS+ are involved in synaptic plasticity and energy homeostasis, and thus appear as plausible biomarkers of this common symptom.

10.
Transplantation ; 103(7): 1514-1522, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30247314

RESUMO

BACKGROUND: Considerable differences exist among the living donor Kidney Exchange Programmes (KEPs) that are in use and being built in Europe, contributing to a variation in the number of living donor transplants (Newsletter Transplant; International figures on donation and transplantation 2016). Efforts of European KEPs to exchange (best) practices and share approaches to address challenges have, however, been limited. METHODS: Experts from 23 European countries, collaborating on the European Network for Collaboration on Kidney Exchange Programmes Cooperation on Science and Technology Action, developed a questionnaire to collect detailed information on the functioning of all existing KEPs in Europe, as well as their opportunities and challenges. Following a comparative analysis, results were synthesized and interpreted by the same experts. RESULTS: The practices, opportunities and challenges reported by 17 European countries reveal that some of the 10 operating programs are mature, whereas others are in earlier stages of development. Over 1300 transplants were performed through existing KEPs up to the end of 2016, providing approximately 8% of their countries' living kidney donations in 2015. All countries report challenges to either initiating KEPs or increasing volumes. Some challenges are shared, whereas others differ because of differences in context (eg, country size, effectiveness of deceased donor program) and ethical and legal considerations (eg, regarding living donation as such, nonrelated donors, and altruistic donation). Transnational initiatives have started in Central Europe, Scandinavia, and Southern Europe. CONCLUSIONS: Exchange of best practices and shared advancement of national programs to address existing challenges, aided by transnational exchanges, may substantially improve access to the most (cost) effective treatment for the increasing number of patients suffering from kidney disease.

11.
Am J Physiol Regul Integr Comp Physiol ; 316(2): R101-R109, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30427725

RESUMO

Interest in individual variation in hormone concentrations is rapidly increasing, particularly with regard to the evolutionary and practical implications. A key aspect of studying individual variation in any labile trait is estimating the degree of within- versus among-individual variation, but at present, we do not have a broad consensus on the extent to which hormone levels are repeatable and what factors might influence repeatability. To address this knowledge gap, we conducted a comprehensive meta-analysis of hormone levels that included 1,132 estimates of repeatability from 368 studies across three fields of study: agriculture, ecology, and medicine. We assessed the influence of sex, age class, sample type, hormone family, type of hormone measure, assay type, number of subjects, number of samples per subject, and sampling interval on repeatability estimates. Overall mean repeatability was 0.58, but estimates differed substantially among study disciplines, being lowest in ecology (0.34), moderate in agriculture (0.52), and relatively high in medicine (0.68). In addition, repeatability decreased slightly as sampling interval increased, and also tended to be higher for peak hormone levels than baseline levels. Overall, hormone levels are moderately repeatable, suggesting that they can potentially be useful indicators of individual variation. However, estimates of repeatability are quite variable among fields, so caution should be used when relying on single samples to assess individual variation.


Assuntos
Agricultura/estatística & dados numéricos , Comportamento Animal/fisiologia , Hormônios/análise , Animais , Ecossistema , Feminino , Humanos , Masculino , Fenótipo , Reprodutibilidade dos Testes
12.
J Anim Ecol ; 88(4): 511-520, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30516829

RESUMO

The expression of individual behaviour as a function of environmental variation (behavioural plasticity) is recognized as a means for animals to modify their phenotypes in response to changing conditions. Plasticity has been studied extensively in recent years, leading to an accumulation of evidence for behavioural plasticity within natural populations. Despite the recent attention given to studying individual variation in behavioural plasticity, there is still a lack of consensus regarding its causes and constraints. One pressing question related to this is whether individual plasticity carries over across temporal and environmental gradients. That is, are some individuals more plastic (responsive) than others in general? Here, we examined the influence of temporal and environmental gradients on individual behavioural responses in a marine gastropod, Littoraria irrorata. We measured individual boldness repeatedly over time and in response to tidal cycle (high vs. low, an index of risk) and daily temperature fluctuations (known to affect metabolism), in a controlled field experiment. On average, boldness increased from high to low tide and with increasing temperature but decreased marginally over time. Individuals also differed in their responses to variation in tide and temperature, but not over time. Those which were relatively bold at high tide (when predation risk is greater) were similarly bold at low tide, whereas shy individuals became much more "bold" at low tide. Most notably, individuals that were more responsive to tide (and thus risk) were also more responsive to temperature changes, indicating that plasticity was correlated across contexts (r = 0.57) and that bolder individuals were least plastic overall. This study provides a rare and possibly first example of consistency of individual behavioural plasticity across contexts, suggesting underlying physiology as a common mechanism, and raises the possibility of correlational selection on plasticity.


Assuntos
Comportamento Animal , Comportamento Predatório , Animais , Personalidade , Fenótipo , Temperatura Ambiente
13.
Orv Hetil ; 159(46): 1905-1912, 2018 11.
Artigo em Húngaro | MEDLINE | ID: mdl-30450936

RESUMO

Patients with end-stage renal disease may exchange their willing, but incompatible donors among each other in centrally coordinated kidney exchange programmes. The aim of this writing is to summarise the results of the ENCKEP COST Action, and describe the lessons learned with regard to the plans for the Hungarian kidney exchange programme. The ENCKEP COST Action had several workshops since 2016 September, and its first working group conducted two surveys that they summarised in two handbooks; our description is based on these resources. There are already 10 national kidney exchange programmes in Europe, the oldest is in the Netherlands (operating since 2004) and the largest in the United Kingdom, where already more than 700 patients received a kidney through this programme in the last ten years. There are a number of countries with plans to start a kidney exchange programme, and international collaborations are also getting established in several regions. Kidney exchange programmes can significantly increase the opportunities of the kidney patients for getting living donor transplants, but for the successful operation of a kidney exchange programme the organisers have to resolve several medical, logistic, optimisation, ethical and legal issues. Orv Hetil. 2018; 159(46): 1905-1912.


Assuntos
Internacionalidade , Falência Renal Crônica/cirurgia , Doadores Vivos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Humanos , Hungria , Falência Renal Crônica/economia , Alocação de Recursos , Obtenção de Tecidos e Órgãos/economia
14.
Rom J Anaesth Intensive Care ; 25(2): 97-101, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30393765

RESUMO

Study objective: Videolaryngoscopes can be fitted either with channeled or non-channeled blades, which may result in a different performance and success of tracheal intubation. We investigated the characteristics of the two different blade types of the commercially available KingVision™ videolaryngoscope. Design: A prospective, randomized, single center investigation study in a urological operation unit of a tertiary hospital. Subjects and Methods: Forty adult patients undergoing elective urological surgery in general anaesthesia with tracheal intubation were randomly allocated into group 1 (channeled videolaryngoscopy, n = 20) and group 2 (non-channeled videolaryngoscopy, n = 20). We measured the times from laryngoscope insertion to recognize the glottis and to conclude tracheal intubation. The number of laryngoscopy/intubation attempts and the degree of visual glottis exposure on a visual analog scale from 0 (glottis not visible) to 10 (glottis fully visible) was assessed. The lowest SpO2 value during airway management was recorded. Results: There was no statistically significant difference in biometric data between the 2 groups. The time from the laryngoscope insertion to glottis recognition with the non-channeled blades was 5 (4-8) s as compared to the channeled ones with 11 (7-14) s (median and range; p = 0.01). Intubation duration was shorter with the channeled blades 17 (12-27) s vs. 29 (25-51) s (median and range; p < 0.001). Number of laryngoscopy/intubation attempts, grades for glottis visibility, intubation difficulty were not different. The lowest SpO2 was 98% in both groups. Conclusions: Videolaryngoscopic glottis recognition time was longer and the total time to secure the airway was shorter with the channeled blades.

15.
Turk J Anaesthesiol Reanim ; 46(5): 348-353, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30263857

RESUMO

Objective: Various drugs are available for general anaesthesia, and the anaesthesiologist in charge may choose the one that is considered as the most appropriate for each specific case. When selecting an anaesthetic drug, its specific pharmacokinetic and pharmacodynamics as well as certain non-pharmacological properties have to be considered. This may lead to decisions that may be justified or unjustified according to scientific evidence and local standards. Methods: In a prospective, single-centre, non-randomised and non-interventional study, 30 attending anaesthetists were interviewed about their drug prescription for general anaesthesia cases scheduled for the next day. The stated reasons for their choices from available alternatives were recorded and analysed for being justified or unjustified. Results: We found 69% of all decisions as justified, while 31% were incorrect, unjustified or random. Female anaesthetists made 83%±15% justified decisions, whereas males achieved a lower performance with 69%±17% justified decisions (p=0.046). Conclusion: To a large proportion, convenience, habit and personal preferences influence the decision-making in choosing the anaesthetic medication. A change of paradigm in the postgraduate education and training seems to be necessary.

16.
Evolution ; 72(10): 2167-2180, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30133698

RESUMO

Interactions between genotypes and environments are central to evolutionary genetics, but such interactions are typically described, rather than predicted from theory. Recent Bayesian models of development generate specific predictions about genotypic differences in developmental plasticity (changes in the value of a given trait as a result of a given experience) based on genotypic differences in the value of the trait that is expressed by naïve subjects. We used these models to make a priori predictions about the effects of an aversive olfactory conditioning regime on the response of Drosophila melanogaster larvae to the odor of ethyl acetate. As predicted, across 116 genotypes initial trait values were related to plasticity. Genotypes most strongly attracted to the odor of ethyl acetate when naïve reduced their attraction scores more as a result of the aversive training regime than those less attracted to the same odor when naïve. Thus, as predicted, the variance across genotypes in attraction scores was higher before than after the shared experience. These results support predictions generated by Bayesian models of development and indicate that such models can be successfully used to investigate how variation across genotypes in information derived from ancestors combines with personal experience to differentially affect developmental plasticity in response to specific types of experience.


Assuntos
Acetatos/metabolismo , Quimiotaxia , Drosophila melanogaster/fisiologia , Genótipo , Animais , Teorema de Bayes , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Meio Ambiente , Larva/genética , Larva/crescimento & desenvolvimento , Larva/fisiologia , Modelos Genéticos , Odorantes/análise , Olfato
17.
Turk J Anaesthesiol Reanim ; 46(1): 57-61, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30140502

RESUMO

Objective: Some anaesthetists are convinced that a long interval since the last relaxant dose may be sufficient to recover from anaesthesia without a pharmacological reversal. We intended to demonstrate that the dosing pattern of rocuronium could not predict the necessity of reversal. Methods: In a cohort analysis, we retrospectively analysed 180 anaesthesia records of adult patients who underwent elective surgical interventions in general anaesthesia and tracheal intubation with rocuronium-induced neuromuscular blockade. The extracted records were divided to 3 post hoc groups of 60 each, according to the reversal method employed at the end of anaesthesia: group N with neostigmine, group S with sugammadex and group Z without pharmacological reversal. All cases were terminated after achieving a train of four ratio of 0.9. Dosing patterns of rocuronium were compared by applying a novel pharmacometric calculation method, residual drug activity coefficient (RDAC), which employs both the administered individual drug doses in mg kg-1 and the timing of each drug administration in relation to the time of extubation. The rocuronium dosing pattern was correlated with the employed method of neuromuscular blockade reversal. Results: The dosing for rocuronium in patients without pharmacological reversal was lower than that in both reversal agent groups (n=0.58±0.21, S=0.58±0.17 and Z=0.47±0.17), but there was still a large overlap in the RDAC. Conclusion: The dosage profile of rocuronium alone cannot predict the possibility to refrain from pharmacological reversal.

18.
Am Nat ; 192(2): 142-154, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30016170

RESUMO

Behavioral ecologists have hypothesized that among-individual differences in resting metabolic rate (RMR) may predict consistent individual differences in mean values for costly behaviors or for behaviors that affect energy intake rate. This hypothesis has empirical support and presently attracts considerable attention, but, notably, it does not provide predictions for individual differences in (a) behavioral plasticity or (b) unexplained variation (residual variation from mean individual behavior, here termed predictability). We outline how consideration of aerobic maximum metabolic rate (MMR) and particularly aerobic scope (= MMR - RMR) can be used to simultaneously make predictions about mean and among- and within-individual variation in behavior. We predict that while RMR should be proportional to an individual's mean level of sustained behavioral activity (one aspect of its personality), individuals with greater aerobic scope will also have greater scope to express behavioral plasticity and/or greater unpredictability in behavior (=greater residual variation). As a first step toward testing these predictions, we analyze existing activity data from selectively bred lines of mice that differ in both daily activity and aerobic scope. We find that replicate high-scope mice are more active on average and show greater among-individual variation in activity, greater among-individual variation in plasticity, and greater unpredictability. These data provide some tentative first support for our hypothesis, suggesting that further research on this topic would be valuable.


Assuntos
Metabolismo Basal , Comportamento Animal/fisiologia , Atividade Motora , Personalidade/fisiologia , Adaptação Psicológica , Aerobiose , Animais , Feminino , Masculino , Camundongos
20.
Trends Cancer ; 4(3): 169-172, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29506667

RESUMO

Age is one of the strongest predictors of cancer and risk of death from cancer. Cancer is therefore generally viewed as a senescence-related malady. However, cancer also exists at subclinical levels in humans and other animals, but its earlier effects on the body are poorly known by comparison. We argue here that cancer is a significant but ignored burden on the body and is likely to be a strong selective force from early during the lifetime of an organism. It is time to adopt this novel view of malignant pathologies to improve our understanding of the ways in which oncogenic phenomena influence the ecology and evolution of animals long before their negative impacts become evident and fatal.


Assuntos
Senescência Celular , Neoplasias , Animais , Humanos
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