Comparative study of the modulation of fructose/sucrose-induced hepatic steatosis by mixed lipid formulations varying in unsaturated fatty acid content

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. NAFLD encompasses a spectrum of diseases, ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and liver failure. The etiology of NAFLD remains unclear but is thought to relate to increased fatty acid flux within the liver that results in toxic fatty acid metabolite production. One source of increased fatty acid flux is fructose/sucrose-induced hepatic lipogenesis. Current treatment for NAFLD encompasses dietary modifications. However, little scientific evidence exists on which to base many dietary recommendations, especially the intake of different types of carbohydrates and fats. We hypothesized that lipid mixtures of unsaturated fatty acids would inhibit lipogenesis and subsequent hepatic steatosis induced by high carbohydrate diets. The aim of this study was to examine the effects of different complex mixtures of fatty acids upon the development of fructose/sucrose-induced hepatic steatosis. METHODS: C57BL/6 mice were randomized to normocaloric chow-based diets that varied in the type of carbohydrate (starch, sucrose, fructose). Animals in each carbohydrate group were further randomized to diets that varied in lipid type (no additional lipid, soybean oil, fish oil, olive/soybean oil, macadamia nut oil). These oils were chosen based upon their content of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, or omega-7 monounsaturated fatty acids. Fatty acid flux in the liver was determine by assessing hepatic lipid content (steatosis). We also assessed fatty acid levels in the plasma and liver of the animals, hepatic lipogenesis activity, hepatic stearoyl-CoA-1 desaturase activity, and hepatic elongase activity. RESULTS: Animals consumed similar amounts of the diets and maintained normal body weights throughout the study. Both sucrose and fructose induced hepatic lipogenesis and steatosis, with fructose being more potent. All mixed lipids similarly inhibited steatosis, limiting lipid content to levels found in the control (starch) animals. Lipogenesis and stearoyl-CoA-1 desaturase activity were increased in the sucrose and fructose groups. Levels of these enzymatic processes remained at baseline in all of the lipid groups. CONCLUSION: This is the first study to compare various complex lipid mixtures, based upon dietary oils with different types of long-chain fatty acids, upon development of sucrose/fructose-induced steatosis. Both carbohydrate source and lipid content appear important for the modulation of steatosis. Moderate intake of complex lipids with high unsaturated to saturated fatty acid ratios inhibited both lipogenesis and steatosis

Extracellular calcium reduction strongly increases the lytic capacity of pneumolysin from streptococcus pneumoniae in brain tissue

Background. Streptococcus pneumoniae causes serious diseases such as pneumonia and meningitis. Its major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, which produces lytic pores at high concentrations. At low concentrations, it has other effects, including induction of apoptosis. Many cellular effects of pneumolysin appear to be calcium dependent. Methods. Live imaging of primary mouse astroglia exposed to sublytic amounts of pneumolysin at various concentrations of extracellular calcium was used to measure changes in cellular permeability (as judged by lactate dehydrogenase release and propidium iodide chromatin staining). Individual pore properties were analyzed by conductance across artificial lipid bilayer. Tissue toxicity was studied in continuously oxygenated acute brain slices. Results. The reduction of extracellular calcium increased the lytic capacity of the toxin due to increased membrane binding. Reduction of calcium did not influence the conductance properties of individual toxin pores. In acute cortical brain slices, the reduction of extracellular calcium from 2 to 1 mM conferred lytic activity to pathophysiologically relevant nonlytic concentrations of pneumolysin. Conclusions. Reduction of extracellular calcium strongly enhanced the lytic capacity of pneumolysin due to increased membrane binding. Thus, extracellular calcium concentration should be considered as a factor of primary importance for the course of pneumococcal meningitis

Phosphorus and Calcium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142245/1/ncp0021.pd

Spectroscopic studies of plasma streams generated in a 1-MJ plasma-focus facility with and without gas-puffing

The main aim of the reported experimental session was to study operational characteristics of a modified PF-1000U facility during a free propagation of a plasma-stream and its interactions with a carbon-fiber composite (CFC) target. The facility was equipped with an axial fast-acting valve for additional gas puffing into a region close to the electrodes outlets. Experiments were carried out with and without the gas puffing in chosen instants before the application of high voltage pulse. The operational regimes of the facility were established by changing these parameters and the initial charging voltage. To record optical spectra of the plasma radiation the use was made of a Mechelle®900 spectrometer coupled with a CCD-camera sensitive in a wavelength range of 300...1100 nm. During all reported experiments the exposition time was equal to 100 ns, but a time delay was changed to obtain data for different discharge phases. The performed spectral measurements enabled to study plasma dynamics, to identify plasma impurities, and to estimate electron densities and temperatures. The electron density in a free-propagating plasma stream was calculated from a linear Stark-effect observed for the Dα spectral line.Главной целью докладываемой экспериментальной сессии было изучение рабочих характеристик модифицированной установки PF-1000U во время свободного распространения плазменного потока и его взаимодействия с углеродной мишенью CFC. Установка была переоснащена специальным быстро действующим клапаном для дополнительного напуска газа в зону фокуса (область, близкую к концам электродов). Эксперименты проводились c импульсным напуском и без напуска газа в выбранные моменты времени до применения импульса высокого напряжения. Рабочие режимы установки PF-1000U определялись изменениями этих параметров и начального зарядного напряжения. Чтобы зарегистрировать оптические спектры плазменного излучения использовался спектрометр Mechelle®900 с подсоединенной к нему CCD-камерой, чувствительной в диапазоне 300…1100 нм. Во время всей серии экспериментов время экспозиции было равно 100 нс, но время задержки спектрометра изменялось для получения данных в различные фазы разряда. Выполненные спектральные измерения касались динамики плазмы, идентификации примесей в плазме, так же как и оценок электронной плотности и температуры. Электронная плотность в свободном плазменном потоке рассчитывалась из линейного штарк-эффекта, наблюдаемого для спектральной линии Dα.Основною метою в експериментальній сесії, що доповідається, було вивчення робочих характеристик модифікованого пристрою PF-1000U під час вільного розповсюдження плазмового потоку та взаємодії з вуглецевою мішенню CFC. Установка була обладнана спеціальним швидким клапаном для додаткового напуску газу в зону фокусу (область, близька до кінців електродів). Експерименти проводились без напуску та з напуском газу до подачі високої напруги. Робочі режими визначались змінами цих параметрів та початкової зарядної напруги. Для того, щоб зареєструвати оптичні спектри випромінювання плазми використовувався спектрометр Mechelle®900 із CCD-камерою, чутливою в діапазоні довжин хвиль 300…1100 нм. Під час всієї серії експериментів час експозиції був 100 нс, але час затримки спектрометра змінювався, щоб отримати дані в різні фази розряду. Проведені спектральні вимірювання стосувались динаміки плазми, ідентифікації домішок у плазмі, так як і оцінок плазмової густини та температури. Електронна густина у вільному плазмовому потоці розраховувалась з лінійного штарк-ефекту, що спостерігався для спектральної лінії Dα

The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Intolerance to enteral nutrition is common in critically ill adults, and may result in significant morbidity including ileus, abdominal distension, vomiting and potential aspiration events. Prokinetic agents are prescribed to improve gastric emptying. However, the efficacy and safety of these agents in critically ill patients is not well-defined. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy and safety of prokinetic agents in critically ill patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library from inception up to January 2016. Eligible studies included randomized controlled trials (RCTs) of critically ill adults assigned to receive a prokinetic agent or placebo, and that reported relevant clinical outcomes. Two independent reviewers screened potentially eligible articles, selected eligible studies, and abstracted pertinent data. We calculated pooled relative risk (RR) for dichotomous outcomes and mean difference for continuous outcomes, with the corresponding 95 % confidence interval (CI). We assessed risk of bias using Cochrane risk of bias tool, and the quality of evidence using grading of recommendations assessment, development, and evaluation (GRADE) methodology. RESULTS: Thirteen RCTs (enrolling 1341 patients) met our inclusion criteria. Prokinetic agents significantly reduced feeding intolerance (RR 0.73, 95 % CI 0.55, 0.97; P = 0.03; moderate certainty), which translated to 17.3 % (95 % CI 5, 26.8 %) absolute reduction in feeding intolerance. Prokinetics also reduced the risk of developing high gastric residual volumes (RR 0.69; 95 % CI 0.52, 0.91; P = 0.009; moderate quality) and increased the success of post-pyloric feeding tube placement (RR 1.60, 95 % CI 1.17, 2.21; P = 0.004; moderate quality). There was no significant improvement in the risk of vomiting, diarrhea, intensive care unit (ICU) length of stay or mortality. Prokinetic agents also did not significantly increase the rate of diarrhea. CONCLUSION: There is moderate-quality evidence that prokinetic agents reduce feeding intolerance in critically ill patients compared to placebo or no intervention. However, the impact on other clinical outcomes such as pneumonia, mortality, and ICU length of stay is unclear

β-alanine supplementation improves in-vivo fresh and fatigued skeletal muscle relaxation speed

Purpose: In fresh muscle, supplementation with the rate-limiting precursor of carnosine, β-alanine (BA), results in a decline in muscle half-relaxation time (HRT) potentially via alterations to calcium (Ca2+) handling. Accumulation of hydrogen cation (H+) has been shown to impact Ca2+ signalling during muscular contraction, carnosine has the potential to serve as a cytoplasmic regulator of Ca2+ and H+ coupling, since it binds to both ions. The present study examined the effect of BA supplementation on intrinsic in-vivo isometric knee extensor force production and muscle contractility in both fresh and fatigued human skeletal muscle assessed during voluntary and electrically evoked (nerve and superficial muscle stimulation) contractions. Methods: Twenty-three males completed two experimental sessions, pre- and post- 28 day supplementation with 6.4 g.day−1 of BA (n=12) or placebo (PLA; n=11). Isometric force was recorded during a series of voluntary and electrically evoked knee extensor contractions. Results: BA supplementation had no effect on voluntary or electrically  evoked isometric force production, or twitch electromechanical delay and time-to-peak tension. There was a significant decline in muscle HRT in fresh and fatigued muscle conditions  during both resting (3±13%; 19±26%) and potentiated (1±15%; 2±20%) twitch contractions. Conclusions: The mechanism for reduced HRT in fresh and fatigued skeletal muscle following BA supplementation is unclear. Due to the importance of muscle relaxation on total energy consumption, especially during short, repeated contractions, BA supplementation may prove to be beneficial in minimising contractile slowing induced by fatigue. Trial registration The trial is registered with Clinicaltrials.gov, ID number NCT02819505

Research on interactions of intense deuterium plasma streams with SiC targets in plasma-focus experiments

The paper presents results of experimental research on emission of the visible radiation (VR) from intense deuterium plasma streams propagating freely within a vacuum chamber or interacting with silicon-carbide (SiC) targets. The investigated pulsed plasma streams were generated by high-current discharges realized within two facilities of the Plasma-Focus (PF) type, i.e. within the PF-1000U facility operated at the IFPiLM and the PF-360U device operated at the NCBJ. Detailed measurements have been carried out using optical emission spectroscopy (OES) technique. Parameters of plasma were estimated from the Dα line only. Structural changes of the irradiated SiC targets were analyzed by means of a scanning electron microscope (SEM) and energy dispersive X-ray spectrometer (EDS).Представлены результаты экспериментальных исследований по эмиссии видимого излучения из интенсивных дейтериевых плазменных потоков свободно распространяющихся в вакуумной камере или взаимодействующих с SiC-мишенями. Исследуемые импульсные плазменные потоки генерировались высокоточными разрядами на двух установках типа плазменный фокус (ПФ). А именно, установка PF-1000U, работающая в IFPiLM, и PF-360U, работающая в NCBJ. Детальные измерения были проведены с использованием оптической эмиссионной спектроскопии (ОЭС). Параметры плазмы были оценены из Dα-линии. Структурные изменения облучаемых SiC-образцов были проанализированы с помощью сканирующего электронного микроскопа (СЭM) и энергии рентгеновского спектрометра (ЭРС).Представлено результати експериментальних досліджень з емісії видимого випромінювання з інтенсивних дейтерієвих плазмових потоків, що вільно розповсюджуються у вакуумній камері чи взаємодіють з SiC-мішенями. Імпульсні плазмові потоки, що досліджувались, генерувались високоточними розрядами на двох установках типу плазмовий фокус (ПФ). А саме, установка PF-1000U, що функціонує в IFPiLM, та PF-360U – у NCBJ. Детальні вимірювання були проведені за допомогою оптичної емісіонної спектроскопії (OEС). Параметри плазми були оцінені з Dα-лінії. Структурні зміни опромінених SiC-мішеней проаналізовані за допомогою скануючого електронного мікроскопа (СEM) та енергії рентгенівського спектрометра (EРС)