We evaluated the relationship of stocking density to survival, growth performance and fin condition of European perch Perca fluviatilis with hand feeding and self-feeders. Hand-fed perch (body weight 19.1 ± 5.1 g and total length 107 ± 9 mm) were reared at 0.5, 1.0, 1.5 and 2.0 fish/L. Self-feeding perch (body weight 25.4 ± 3.9 g and total length 128 ± 7 mm) were reared at stocking densities of 0.6, 1.0 and 1.4 fish/L. Pond-reared perch served as a comparison group for fin damage assessment. We found no differences in survival rate among stocking densities with either feeding method. Hand-fed fish displayed the highest weight gain and SGR at stocking density of 0.5 fish/L. The self-feeding fish showed a non-linear association of weight gain with stocking density with the highest growth at 1.0 fish/L. Fin length was noticeably greater in pond-reared fish compared with RAS-reared fish regardless of feeding method. In both experiments, fin length relative to standard length showed a negative relationship with stocking density, with pectoral fins showing the greatest effect. Fin condition deteriorated with increasing stocking density, and growth was highest at 0.5 and 1.0 fish/L in hand-fed and self-feeding fish, respectively.

• MeSH
• hustota populace MeSH
• metody výživy veterinární   MeSH
• okounovití růst a vývoj   zranění   fyziologie   MeSH
• ploutve zvířat zranění   patologie   MeSH
• rybářství * MeSH
• vodní hospodářství * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

The effects of high-dose ethanol intoxication on cognitive flexibility processes are not well understood, and processes related to hangover after intoxication have remained even more elusive. Similarly, it is unknown in how far the complexity of cognitive flexibility processes is affected by intoxication and hangover effects. We performed a neurophysiological study applying high density electroencephalography (EEG) recording to analyze event-related potentials (ERPs) and perform source localization in a task switching paradigm which varied the complexity of task switching by means of memory demands. The results show that high-dose ethanol intoxication only affects task switching (i.e. cognitive flexibility processes) when memory processes are required to control task switching mechanisms, suggesting that even high doses of ethanol compromise cognitive processes when they are highly demanding. The EEG and source localization data show that these effects unfold by modulating response selection processes in the anterior cingulate cortex. Perceptual and attentional selection processes as well as working memory processes were only unspecifically modulated. In all subprocesses examined, there were no differences between the sober and hangover states, thus suggesting a fast recovery of cognitive flexibility after high-dose ethanol intoxication. We assume that the gamma-aminobutyric acid (GABAergic) system accounts for the observed effects, while they can hardly be explained by the dopaminergic system.

• MeSH
• cingulární gyrus fyziologie   patofyziologie   MeSH
• dechové testy MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• evokované potenciály fyziologie   MeSH
• GABA MeSH
• kognice fyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek fyziologie   patofyziologie   MeSH
• nervový přenos fyziologie   MeSH
• otrava alkoholem patofyziologie   psychologie   MeSH
• plnění a analýza úkolů MeSH
• pozornost MeSH
• reakční čas MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

• MeSH
• anticholesteremika * terapeutické užití   MeSH
• ateroskleróza * farmakoterapie   MeSH
• homozygot MeSH
• homozygotní familiární hypercholesterolemie * MeSH
• hyperlipoproteinemie typ II * diagnóza   genetika   terapie   MeSH
• LDL-cholesterol genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIMS: This European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients. METHODS: Evidence-based review. RESULTS: Statin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus. CONCLUSIONS: This guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.

• MeSH
• anticholesteremika * škodlivé účinky   MeSH
• ateroskleróza * farmakoterapie   prevence a kontrola   MeSH
• diabetes mellitus 2. typu * MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• statiny * terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. METHODS: Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. RESULTS: Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. CONCLUSIONS: Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA.

• MeSH
• artritida experimentální metabolismus   MeSH
• chondrocyty metabolismus   MeSH
• kloubní chrupavka metabolismus   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• membránové glykoproteiny metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• osteoartróza metabolismus   MeSH
• osteofyt metabolismus   MeSH
• receptor Notch1 metabolismus   MeSH
• signální transdukce MeSH
• stupeň závažnosti nemoci MeSH
• transkripční faktor HES1 metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. METHODS: Sebelipase alfa (1mg/kg or 3mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. RESULTS: 216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of -58% and -40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were -60%, -39%, -36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. CONCLUSIONS: Long-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184).

• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• dospělí MeSH
• játra patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• mladý dospělý MeSH
• rekombinantní proteiny aplikace a dávkování   škodlivé účinky   MeSH
• rozvrh dávkování léků MeSH
• sterolesterasa aplikace a dávkování   škodlivé účinky   nedostatek   MeSH
• Wolmanova nemoc krev   farmakoterapie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Prolonged cultivation of separated rat lung mast cells (LMC) in vitro is necessary to better investigate a possible role of LMC in different stages of tissue remodeling induced by hypoxia. Rat lung mast cells (LMC) were separated using a protocol including an improved proteolytic extraction and two subsequent density gradient separations on Ficoll-Paque PLUS and a new generation of Percoll, i.e. Percoll PLUS. Instead of usual isotonic stock Percoll solution, an alternative "asymptotically isotonic" stock solution was more successful in our density separation of LMC on Percoll PLUS. Separated cells were cultivated for six days in media including stem cell factor, interleukins IL-3 and IL-6, and one of two alternative mixtures of antibiotics. These cultivations were performed without any contamination and with only rare changes in cell size and morphology. Model co-cultivation of two allogenic fractions of LMC often caused considerable rapid changes in cell morphology and size. In contrast to these observations no or rare morphological changes were found after cultivation under hypoxic conditions. In conclusions, we modified separation on Percoll PLUS to be widely used, altered LMC separation with respect to purposes of long-lasting cultivation and observed some model morphological changes of LMC.

• MeSH
• centrifugace - gradient hustoty MeSH
• financování organizované MeSH
• isotonické roztoky chemie   MeSH
• krysa rodu rattus MeSH
• mastocyty cytologie   MeSH
• oxid křemičitý chemie   MeSH
• plíce cytologie   metabolismus   MeSH
• povidon chemie   MeSH
• separace buněk metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

An experiment to reveal functional response and heifers' performance to sward characteristics and forage chemical composition was conducted for 5 years in rotational (RSS) and continuous (CSS) stocking systems on native species-rich upland grassland. We measured sward characteristics, forage chemical composition, heifers' grazing behavior and live-weight gains from July to September. Mean sward surface height was lower on CSS than on RSS; grass and forb density, and white clover stolon length, were similar. Herbage on CSS had higher crude protein content and lower crude fiber content than on RSS. No difference existed in time budgets of grazing, ruminating and resting between stocking systems and season, while grazing rates were higher on CSS. Stocking rate was 1671 and 1332 kg per ha on CSS and RSS, individual daily live-weight gain 683 and 652 g on CSS and RSS. Gain per ha was 20 kg higher on CSS. Results suggested stocking systems on native species-rich grassland had no effect on activity time budgets or animal performance. Both RSS and CSS allow similar outputs for stocking rates in terms of individual daily live-weight gain. Key parameters determining heifers' behavior and performance were sward height, grass and forb density in the sward, and content of crude fiber and protein in forage.

• MeSH
• býložravci fyziologie   MeSH
• hmotnostní přírůstek MeSH
• krmivo pro zvířata * MeSH
• lipnicovité * MeSH
• roční období MeSH
• skot růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• skot růst a vývoj   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A novel sampling scheme, using a combination of electrofishing, visual exploration by scuba divers, two types of fyke nets and longlines, was tested in four reservoirs (including their inlets and outlets) to monitor a population of burbot Lota lota. This was supplemented by fry trawling and vertical hydro-acoustics, to detect L. lota larvae in two deep reservoirs that have had a long-term stocking programme. The majority of the L. lota detected were juveniles, captured by electrofishing in the littoral zones of the reservoirs and in running waters. Older individuals were rarely captured with longlines or fyke nets in deeper zones or structured habitats within the reservoirs. A combination of multiple sampling methods provided an assessment of the whole population. Population establishment could not be demonstrated as the age structure of the sampled fish corresponded with that of the stocked fish. Low post-stocking survival, migratory behaviour, interactions with other species and warmer water temperatures are considered the potential drivers for unsuccessful establishment of L. lota populations in these reservoirs.

• MeSH
• Gadiformes fyziologie   MeSH
• hustota populace MeSH
• larva fyziologie   MeSH
• ohrožené druhy MeSH
• populační dynamika MeSH
• rybářství MeSH
• zachování přírodních zdrojů * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

• MeSH
• benzoxazoly škodlivé účinky   terapeutické užití   MeSH
• bezpečnost pacientů MeSH
• biologické markery krev   MeSH
• butyráty škodlivé účinky   terapeutické užití   MeSH
• cílená molekulární terapie MeSH
• dyslipidemie krev   diagnóza   farmakoterapie   MeSH
• hodnocení rizik MeSH
• hypolipidemika škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci krev   diagnóza   prevence a kontrola   MeSH
• konsensus MeSH
• lidé MeSH
• lipidy krev   MeSH
• PPAR alfa agonisté   metabolismus   MeSH
• rizikové faktory MeSH
• signální transdukce MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH