Additive effect
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Autor sledoval 23 pacientov s primárnym glaukómom s otvoreným uhlom liečených pilocarpinom, timololom, betopticom a latanoprostom. Pre nedostatočnú kompenzáciu základného ochorenia bol pridaný dorzolamid a pacienti boli sledovaní po dobu 12 mesiacov. Všetky kombinácie signifikantne znižovali vnútroočný tlak v dlhodobom sledovaní. Najväčší pokles bol pri kombinácii prostaglandínového analógu a dorzolamidu.
The author investigated 23 patients with primary open angle glaucoma treated with pilocarpine, timolol, betoptic and latanoprost. Because of inadequate compensation of the basic disease dorsolamide was added and the patients were followed up for a 12-month period. All combinations decreased significantly the intraocular pressure during the long-term follow up. The greatest decrease was recorded after a combination of a prostaglandin analogue and dorsolamide.
V práci sa interpretujú experimentálne výsledky z porovnania aplikácie dvoch základných antiglaukómových liekov do spojovkového vaku u zdravých králikov z kmeňa činčila. Aplikovaný bol 2% pilokarpín a 0,25% Timoptol (Timololi maleas, Léčiva) samotný, v kombinácii aplikácie oboch za sebou, resp. oboch súčasne. Najväčší účinok na šírku pupily i na VOT do 60. minúty mala aplikácia najprv pilokarpínu, potom Timoptolu, resp. po 60. minúte najefektívnejšia bola zmes oboch látok. Tento efekt sa vysvetluje aditívnym pôsobením cez interakčne vznik- nuté nové látky (metabolity). Pritom pilokarpín, ako látka cholínergného cha- rakteru, vyvoláva zvýšenú tvorbu komorového moku a tým aj zvýšený prísun voľných amínokyselín do výbežkov vráskovca a komorového moku. Timoptol potom interaguje so zvýšeným množstvom voľných amínokyselín, a tým vzniká väčšie a časovo dlhšie trvajúce zníženie VOT ako po pôsobení samotnej novovznik- nutej cholínergickej alebo samotnej novovzniknutej adrenergnej látke.
In the submitted paper experimental results are interpreted comparing the administration of two fundamental anti-glaucomatous drugs into the conjunctiv- cal sac of healthy rabbits of the Chinchilla strain. The authors administered 2% pilocarpine and 0.25% Timoptol(Timololi maleas, Léeiva) alone, as combined consecutive administration and concurrent administration. The greatest effect on the width of the pupil and on IOP was exerted before 60 minutes by adminis- tration of pilocarpine, then Timoptol resp. And after 60 minutes the mixture of the two substances was most effective. This effect is explained by the additive action via substances produced by interaction (metabolites). Pilocarpine being a cholinergic substance promotes formation of the vitreous fluid and thus also an increased supply of free amino acids into ciliary body processes and the vitreous fluid. Timoptol then interacts with the increased amount of free amino acids and thus a greater and longer reduction of VOT occurs than after the action of newly formed cholinergic or newly formed adrenergic substances alone.
- Klíčová slova
- TIMOPTOL (TIMOLOLI MALEAS, LÉČIVA),
- MeSH
- beta blokátory aplikace a dávkování terapeutické užití MeSH
- fixní kombinace léků MeSH
- glaukom farmakoterapie MeSH
- králíci MeSH
- parasympatomimetika aplikace a dávkování terapeutické užití MeSH
- pilokarpin aplikace a dávkování terapeutické užití MeSH
- pupila účinky léků MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
- MeSH
- beta blokátory MeSH
- biomedicínský výzkum MeSH
- dospělí MeSH
- fixní kombinace léků MeSH
- hypotonické roztoky MeSH
- lidé středního věku MeSH
- lidé MeSH
- srdeční frekvence účinky léků MeSH
- vápník antagonisté a inhibitory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- konzervační prostředky farmaceutické chemie MeSH
- lidé MeSH
- transplantáty MeSH
- zuby transplantace MeSH
- Check Tag
- lidé MeSH
The combination of plant-derived compounds with anti-diabetic agents to manage hepatic steatosis closely associated with diabetes mellitus may be a new therapeutic approach. Silymarin, a complex of bioactive substances extracted from Silybum marianum, evinces an antioxidative, anti-inflammatory, and hepatoprotective activity. In this study, we investigated whether metformin (300 mg/kg/day for four weeks) supplemented with micronized silymarin (600 mg/kg/day) would be effective in mitigating fatty liver disturbances in a pre-diabetic model with dyslipidemia. Compared with metformin monotherapy, the metformin-silymarin combination reduced the content of neutral lipids (TAGs) and lipotoxic intermediates (DAGs). Hepatic gene expression of enzymes and transcription factors involved in lipogenesis (Scd-1, Srebp1, Pparγ, and Nr1h) and fatty acid oxidation (Pparα) were positively affected, with hepatic lipid accumulation reducing as a result. Combination therapy also positively influenced arachidonic acid metabolism, including its metabolites (14,15-EET and 20-HETE), mitigating inflammation and oxidative stress. Changes in the gene expression of cytochrome P450 enzymes, particularly Cyp4A, can improve hepatic lipid metabolism and moderate inflammation. All these effects play a significant role in ameliorating insulin resistance, a principal background of liver steatosis closely linked to T2DM. The additive effect of silymarin in metformin therapy can mitigate fatty liver development in the pre-diabetic state and before the onset of diabetes.
- Publikační typ
- časopisecké články MeSH
- MeSH
- draslík farmakologie MeSH
- HeLa buňky účinky léků MeSH
- lidé MeSH
- vápník farmakologie MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- MeSH
- beta blokátory MeSH
- biomedicínský výzkum MeSH
- dospělí MeSH
- fixní kombinace léků MeSH
- hypotonické roztoky MeSH
- lidé středního věku MeSH
- lidé MeSH
- srdeční frekvence účinky léků MeSH
- vápník antagonisté a inhibitory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
Introduction: Spinal cord (SC) pathology is strongly associated with disability in multiple sclerosis (MS). We aimed to evaluate the association between focal and diffuse SC abnormalities and spinal cord volume and to assess their contribution to physical disability in MS patients. Methods: This large sample-size cross-sectional study investigated 1,249 patients with heterogeneous MS phenotypes. Upper cervical-cord cross-sectional area (MUCCA) was calculated on an axial 3D-T2w-FatSat sequence acquired at 3T using a novel semiautomatic edge-finding tool. SC images were scored for the presence of sharply demarcated hyperintense areas (focal lesions) and homogenously increased signal intensity (diffuse changes). Patients were dichotomized according EDSS in groups with mild (EDSS up to 3.0) and moderate (EDSS ≥ 3.5) physical disability. Analysis of covariance was used to identify factors associated with dichotomized MUCCA. In binary logistic regression, the SC imaging parameters were entered in blocks to assess their individual contribution to risk of moderate disability. In order to assess the risk of combined SC damage in terms of atrophy and lesional pathology on disability, secondary analysis was carried out where patients were divided into four categories (SC phenotypes) according to median dichotomized MUCCA and presence/absence of focal and/or diffuse changes. Results: MUCCA was strongly associated with total intracranial volume, followed by presence of diffuse SC pathology, and disease duration. Compared to the reference group (normally appearing SC, MUCCA>median), patients with the most severe SC changes (SC affected with focal and/or diffuse lesions, MUCCA
- Publikační typ
- časopisecké články MeSH
