UNLABELLED: PURPOSE : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.
- MeSH
- antihypertenziva škodlivé účinky MeSH
- benzoáty * MeSH
- beta-alanin analogy a deriváty MeSH
- bimatoprost terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- glaukom s otevřeným úhlem * diagnóza farmakoterapie MeSH
- latanoprost škodlivé účinky MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oční hypertenze * diagnóza farmakoterapie MeSH
- oční roztoky MeSH
- prospektivní studie MeSH
- timolol škodlivé účinky MeSH
- tonometrie oční MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Thank you very much for your comment [...].
- MeSH
- beta-alanin * aplikace a dávkování MeSH
- karnosin * MeSH
- lidé MeSH
- potravní doplňky * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
infekce a stres v raném věku během zranitelného období vývoje cns souvisejí se zvýšeným rizikem vzniku neuropsychiatrických poruch, jako je schizofrenie. na základě teorie dvojího zásahu u schizofrenie je hypoteticky ke spuštění poruchy nutný ještě druhý inzult rùzné modality. neonatální aplikace lipopolysacharidu (lPs, známého také jako endotoxin) u potkanù je uznávaným modelem vedoucím k behaviorálnímu deficitu a neurokognitivním poruchám na podkladě imunitní stimulace v raném věku a používá se jako neurovývojový model psychózy. V této práci jsme na modelu potkana studovali, jak neonatální podání lPs spolu s dysbiózou vyvolanou chronickou léčbou antibiotiky jako druhým zásahem na základě teorie dvojího zásahu ovlivní metabolické dráhy pomocí necílené metabolomické analýzy. hodnotili jsme rozdíly mezi metabolomy kontrolní a testovací skupiny (vystavené lPs a/nebo léčbě antibiotiky), abychom zjistili rozdíly mezi jejich metabolitovými profily. Vzorky skupiny léčené lPs vykazovaly pozoruhodné metabolomické změny ve srovnání s kontrolními subjekty. Jako nejvíce ovlivněné divergentní dráhy byly určeny dráhy pyrimidinového metabolismu a dráhy biosyntézy pantothenátu a koenzymu a (coa); p-hodnota upravená podle gama je 0,04275 a 0,04278. Léčba ATB nevedla k žádným změnám metabolomu, a naopak maskovala účinky vyvolané aplikací lPs. S odkazem na tyto údaje jsme schopni naznačit, že neonatální výzva LPS hraje významnou roli v rozkladu pyrimidinového metabolismu a drah biosyntézy pantothenátu a coa, které by mohly být identifikovány jako metabolické dráhy zapojené do patogeneze schizofrenie. Vzhledem k pøedběžné povaze naší studie je nutné naše zjištění ověøit v budoucím výzkumu schizofrenie.
infections and stress in early life, during a vulnerable development period of the cns, are related to an increased risk of the development of neuropsychiatric disorders such as schizophrenia. Based on the dual-intervention theory of schizophrenia, a second insult modality is hypothesized to be required to trigger the disorder. neonatal lipopolysaccharide (lPs, also known as endotoxin) treatment in rats is an acknowledged model for inducing the behavioral deficits and neurocognitive impairments caused by an early-life immune challenge and is used as a neurodevelopmental model of psychosis. in the present work, we studied in the rat model how the neonatal lPs administration along with dysbiosis induced by chronic antibiotic treatment as a second hit based on the dual hit theory will affect metabolic pathways by an untargeted metabolomic analysis. We have evaluated differences between the metabolome of control and test groups (exposed to lPs and/or antibiotic treatment) to determine differences between their metabolite profiles. the lPs-treated group samples have exhibited notable metabolomic changes compared to the control subjects. the most affected divergent pathways were determined as Pyrimidine metabolism and Pantothenate and coenzyme a (coa) biosynthesis pathways (the gamma-adjusted p-values are 0.04275 and 0.04278, respectively). the atB treatment did not result in any changes in metabolome and, on the contrary, masked the effects induced by lPs treatment. referring to these data, we are able to suggest that a neonatal lPs challenge plays a significant role in the discomposing Pyrimidine metabolism and Pantothenate and coa biosynthesis pathways, which could be identified as metabolism pathways involved in schizophrenia pathogenesis. Due to the preliminary nature of our study, it is necessary to confirm our findings in future schizophrenia research
- MeSH
- antibakteriální látky toxicita MeSH
- dysbióza komplikace MeSH
- koenzym A metabolismus účinky léků MeSH
- krysa rodu rattus MeSH
- kyselina pantothenová metabolismus MeSH
- lidé MeSH
- lipopolysacharidy toxicita MeSH
- metabolické sítě a dráhy MeSH
- metabolické vedlejší účinky léčivých látek toxicita MeSH
- metabolom účinky léků MeSH
- modely nemocí na zvířatech MeSH
- novorozenec MeSH
- prenatální poškození * chemicky indukované psychologie MeSH
- pyrimidiny metabolismus MeSH
- schizofrenie * chemicky indukované MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- novorozenec MeSH
OBJECTIVES: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older adults in developed countries. Although many risk factors are known, the pathogenesis of AMD is still unclear. However, oxidative stress probably plays a vital role in the process of AMD. The increasing prevalence of AMD, risk of vision loss, limited treatment of dry form, expensive treatment of wet form, and decreased quality of life are factors that lead to considering modifiable risk factors of AMD, such as nutrition. This is the first study describing the relationship between dietary habits, dietary nutrient intake and AMD in the Czech Republic. METHODS: In this research, a total of 93 cases with AMD and 58 controls without AMD and cataracts participated. All participants were ophthalmologically examined at the Clinic of Eye Treatments at the University Hospital Brno. Data were collected using a pre-tested self-report questionnaire in a face-to-face interview. Food consumption frequency was assessed by an 18-item semiquantitative food-frequency questionnaire (FFQ). Dietary nutrient intakes were calculated from a 24-hour recall. RESULTS: Patients with AMD compared with controls had significantly higher consumption of legumes and lower consumption of meat products, salt and salty products. In men, we found statistically significant differences in alcohol consumption. The case group consumed alcoholic beverages more frequently (median: 2 times a week) than the control group (median: 1-3 times a month). No differences in alcohol consumption were found in women. In comparison to the case group, the control group had a significantly higher dietary intake of energy (5,783.8 vs. 4,849.3 kJ/day; p = 0.002), proteins (65.3 vs. 52.3 g/day; p = 0.002), fats (57.6 vs. 49.4 g/day; p = 0.046), saturated fatty acids (21.7 vs. 18.9 g/day; p = 0.026), carbohydrates (150.4 vs. 127.1 g/day; p = 0.017), dietary fibre (13.2 vs. 11.3 g/day; p = 0.044), vitamin B2 (1.0 vs. 0.9 mg/day; p = 0.029), vitamin B3 (13.9 vs. 10.0 mg/day; p = 0.011), pantothenic acid (3.5 vs. 2.8 mg/day; p = 0.001), vitamin B6 (1.3 vs. 1.0 mg/day; p = 0.001), potassium (1,656.5 vs. 1,418.0 mg/day; p = 0.022), phosphorus (845.4 vs. 718.7 mg/day; p = 0.020), magnesium (176.5 vs. 143.0 mg/day; p = 0.012), copper (1.0 vs. 0.8 mg/day; p = 0.011), and zinc (7.1 vs. 6.1 mg/day; p = 0.012) counted from a 24-hour recall. CONCLUSIONS: According to FFQ, dietary habits in the patients with AMD and controls were similar. In men from the case group, we found statistically significant higher alcohol consumption. According to a 24-hour recall, the controls achieved recommended dietary intakes rather than cases. In comparison to the case group, the control group had a significantly higher dietary intake of energy, proteins, fats, saturated fatty acids, carbohydrates, dietary fibre, vitamin B2, vitamin B3, pantothenic acid, vitamin B6, potassium, phosphorus, magnesium, copper, and zinc.
- MeSH
- dieta MeSH
- dietní tuky MeSH
- draslík MeSH
- energetický příjem MeSH
- fosfor MeSH
- hořčík * MeSH
- kvalita života MeSH
- kyselina pantothenová MeSH
- lidé MeSH
- makulární degenerace * epidemiologie chemicky indukované MeSH
- mastné kyseliny MeSH
- měď MeSH
- niacinamid MeSH
- potravní vláknina MeSH
- přijímání potravy MeSH
- riboflavin MeSH
- senioři MeSH
- stravovací zvyklosti MeSH
- studie případů a kontrol MeSH
- vitamin B6 MeSH
- zinek MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting precursor of carnosine and is among the most used sports supplements for improving athletic performance. However, carnosine, its metabolite N-acetylcarnosine, and the synthetic derivative zinc-L-carnosine have recently been gaining popularity as supplements in human medicine. These molecules have a wide range of effects-principally with anti-inflammatory, antioxidant, antiglycation, anticarbonylation, calcium-regulatory, immunomodulatory and chelating properties. This review discusses results from recent studies focusing on the impact of this supplementation in several areas of human medicine. We queried PubMed, Web of Science, the National Library of Medicine and the Cochrane Library, employing a search strategy using database-specific keywords. Evidence showed that the supplementation had a beneficial impact in the prevention of sarcopenia, the preservation of cognitive abilities and the improvement of neurodegenerative disorders. Furthermore, the improvement of diabetes mellitus parameters and symptoms of oral mucositis was seen, as well as the regression of esophagitis and taste disorders after chemotherapy, the protection of the gastrointestinal mucosa and the support of Helicobacter pylori eradication treatment. However, in the areas of senile cataracts, cardiovascular disease, schizophrenia and autistic disorders, the results are inconclusive.
Celosvětově dochází ke stárnutí populace. Zdravotní péče by se měla na tuto situaci připravit a hledat možnosti, jak vylepšit, prodloužit a zkvalitnit život stárnoucí populace. Stárnutí je spojeno se změnami fyziologických funkcí, jako jsou například změny v aktivitě kosterního svalstva, úbytek svalové hmoty a snížení silové aktivity, změny v kostní tkáni či pokles senzorických a kognitivních funkcí. Deteriorace lidského organismu ve stáří může být spojena právě se sníženými tkáňovými koncentracemi karnosinu, kdy dochází k snížení ochrany membrán buněk před oxidačním poškozením. Zdá se, že konzumací potravin bohatých na karnosin nebo obohacením diety β-alaninem by bylo možné tyto degenerativní procesy zpomalit. Aminokyselina β-alanin je jedním z celosvětově nejpoužívanějších sportovních doplňků, které zlepšují výkon při cvičení, protože je prekurzorem karnosinu, který důležitý pro činnost příčně pruhovaného svalstva. Tato práce má za cíl informovat o suplementaci β-alaninem, prekurzorem karnosinu, která představuje jednu z mála prokázaných dietních intervencí, které by mohly pomoci nejen v boji proti stárnutí a úbytku svalové hmoty, ale i v prevenci dalších onemocnění – senilní katarakty, neurodegenerativních onemocnění a onemocnění periferních tepen a žil.
Globally, the population is ageing. Healthcare should prepare for this situation and look for ways to improve, prolong and improve the quality of life of the ageing population. Ageing is associated with changes in physiological functions, such as changes in skeletal muscle activity, loss of muscle mass and reduced strength, changes in bone tissue and a decline in sensory and cognitive functions. Deterioration of the human body in old age may be associated with reduced tissue concentrations of carnosine, whereby the protection of cell membranes from oxidative damage is reduced. It seems that by consuming foods rich in carnosine or by enriching the diet with β-alanine, these degenerative processes could be slowed down. The amino acid β-alanine is one of the world‘s most widely used sports supplements to improve exercise performance because it is a precursor of carnosine, which is important for striated muscle function. This paper aims to report on supplementation with β-alanine, a precursor of carnosine, which represents one of the few proven dietary interventions that could help not only in the fight against aging and muscle loss, but also in the prevention of other diseases such as senile cataracts, neurodegenerative diseases and peripheral artery and vein disease.
- MeSH
- beta-alanin * terapeutické užití MeSH
- karnosin * terapeutické užití MeSH
- katarakta prevence a kontrola MeSH
- kognice účinky léků MeSH
- lidé MeSH
- onemocnění periferních cév prevence a kontrola MeSH
- sarkopenie prevence a kontrola MeSH
- stárnutí účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments. OBJECTIVES: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. RESULTS: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. CONCLUSIONS: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- činnosti denního života MeSH
- dvojitá slepá metoda MeSH
- Hallervordenův-Spatzův syndrom * farmakoterapie genetika MeSH
- kyselina pantothenová analogy a deriváty MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Karnozin (β-alanyl-L-histidin) je dipeptid, tvořený aminokyselinou β-alaninem a L-histidinem. Karnozin a obě aminokyseliny se vyskytují v mozku a kosterním svalstvu všech obratlovců. Karnozin v buňkách mozkové tkáně chrání intracelulární bílkoviny před jejich poškozením kyslíkovými radikály, glykací a tvorbou příčných vazeb mezi jednotlivými řetězci bílkovin. V kosterním svalstvu karnozin snižuje svalovou únavu způsobenou zvýšenou koncentrací kyseliny mléčné, která vede k poklesu pH. S rostoucím biologickým věkem klesá koncentrace karnozinu jak v buňkách mozkové tkáně, tak v bílých svalových vláknech kosterního svalstva, čímž dochází k zhoršování senzorických a kognitivních funkcí a úbytku svaloviny. Tyto degenerativní procesy lze zpomalit konzumací potravin bohatých na karnozin nebo doplňováním diety β-alaninem. β-alanin určuje rychlost tvorby karnozinu a jeho koncentraci v buňkách mozkové a svalové tkáně. Článek shrnuje současné názory medicíny na roli karnozinu v procesu stárnutí lidského organismu a významu obohacování diety β-alaninem.
Carnosine (β-alanyl-L-histidine) is a dipeptide composed of the amino acid β-alanine and the L-histidine. Carnosine and both amino acids are found in the brain and skeletal muscle of all vertebrates. The physiological function of carnosine in brain tissue is to protect intracellular proteins from damage by oxygen radicals, modification by glycation and formation of cross-links between protein chains. In skeletal muscle, carnosine reduces muscle fatigue caused by increased lactic acid levels and decreased tissue pH. With increasing biological age, carnosine concentration in both brain tissue and white skeletal muscle fibres decreases. There is a loss of muscle mass (sarcopenia) and deterioration of sensory and cognitive functions. These degenerative processes can be delayed by consuming carnosine-rich foods or diet supplemented with pure β-alanine. This amino acid determines the rate of endogenic carnosine synthesis and thus its concentration in brain and muscle tissues. This article is an overview of the present knowledge on the role of carnosine in the process of aging and the importance of the diet enrichment with β-alanine or carnosine.
V současné době se k terapii ran používá velké množství krycích prostředků různého složení i účinků. Patří mezi ně i krytí filmová, kde je jedním z perspektivních materiálů pro přípravu sodná sůl karboxymethylcelulosy (NaCMC) jako látka přírodního původu s výbornými filmotvornými vlastnostmi. Uplatnění nachází zejména v oblasti absorpčních krytí; filmy na rány z tohoto materiálu zatím využití v praxi nemají. Nevyužitý potenciál nabízí rovněž dexpanthenol, látka hojně využívaná v dermatologii. Proto cílem této práce byla příprava filmů z textilní NaCMC s dexpanthenolem metodou odpaření rozpouštědla a jejich následné fyzikálně-chemické hodnocení. Přítomnost mikrofibrilárních vláken částečně substituované karboxymethylcelulosy společně s její kyselou formou (HCMC), vznikající během přípravy, zajistila optimální parametry pro aplikaci na ránu jako je nasákavost, pH a mechanické vlastnosti. Filmy vykazovaly vyhovující hmotnostní, a ty s dexpanthenolem také obsahovou stejnoměrnost.
Currently, a wide variety of wound dressings of varying composition and effects is used to treat wounds. These include also film dressings where one of the promising materials for its preparation is sodium carboxymethylcellulose (NaCMC) as a material of natural origin with excellent film-forming properties. Its application is particularly in the field of absorbent dressings, films for wounds from this material are not used in practice yet. Hidden potential offers also dexpanthenol, a substance widely used in dermatological practice. Therefore, the aim of this research was to prepare films from textile NaCMC with dexpanthenol by the solvent evaporation method and their subsequent physicochemical evaluation. The presence of microfibrillar fibers of partially substituted carboxymethylcellulose together with HCMC has ensured optimal parameters for wound application such as pH, swelling and mechanical properties. The films showed satisfactory mass content uniformity and those with dexpanthenol also drug content uniformity.
BACKGROUND: Panthenol is an active substance used in dermatology to protect the health of the skin, to treat defects in the morphology of the stratum corneum. In cosmetology, hydrating, softening, and barrier function of panthenol are utilized. Detailed studies evaluating the efficacy of panthenol in cosmetic and pharmaceutical semisolid formulations and establishing its optimum concentration are needed. OBJECTIVES: To investigate whether an addition of 5-13 wt% panthenol in o/w and w/o emulsions increases hydration and supports the barrier properties of the skin. Rheological properties and sensory analysis of prepared formulations are supplemented. METHODS: Noninvasive instrumental methods in vivo were used. The hydration and barrier effect of semisolid formulations on the skin were observed for 48 hour; testing was conducted on 40 women. The effect was compared with formulations without any content of panthenol. The rheological and organoleptic properties of the formulations were evaluated. RESULTS: After applying either form of the formulations containing 7-11 wt% of panthenol hydration of the skin increased, transepidermal water loss decreased. pH of the skin shifted toward neutral after application of tested formulations. The rheological properties of the formulations were influenced by the type of vehicle, the amount of panthenol, and temperature. Sensory evaluation of both semisolid forms revealed statistically significant differences in o/w formulations with regard to spreadability. CONCLUSIONS: The presence of panthenol in an o/w and w/o semisolid formulations significantly enhances skin barrier repair and hydration of the stratum corneum. Better vehicle for the active substance as regards hydration proved o/w formulations.
- MeSH
- čití, cítění účinky léků MeSH
- dermatologické látky farmakologie MeSH
- dospělí MeSH
- emulze farmakologie MeSH
- epidermis účinky léků fyziologie MeSH
- fyziologie kůže účinky léků MeSH
- hydrofobní a hydrofilní interakce MeSH
- kosmetické přípravky farmakologie MeSH
- kyselina pantothenová analogy a deriváty farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- perspiratio insensibilis účinky léků MeSH
- příprava léků MeSH
- reologie MeSH
- voda metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
