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8632. Inhalt
- Format:
- Type:
- model:internalpart and TEXT
- Language:
- Czech
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
8633. Inhibice PCSK9 jako nová naděje pro nemocné s familiární hypercholesterolemií, statinovou intolerancí a posléze pro všechny pacienty v nejvyšším kardiovaskulárním riziku? Zaměřeno na alirokumab – Praluent?
- Creator:
- Češka, Richard
- Format:
- print, text, and regular print
- Type:
- model:article, article, Text, přehledy, and TEXT
- Subject:
- lidé, serinové endopeptidasy, konvertasy proproteinů--antagonisté a inhibitory, monoklonální protilátky--aplikace a dávkování--farmakologie--terapeutické užití, kardiovaskulární nemoci--prevence a kontrola, hypercholesterolemie--farmakoterapie, hyperlipoproteinemie typ II--farmakoterapie, LDL-cholesterol--účinky léků, injekce subkutánní, hypolipidemika--aplikace a dávkování--farmakologie--terapeutické užití, alirocumab, and PCSK9
- Language:
- Czech and English
- Description:
- V současné době jsou jak celosvětově (alirokumab byl prvním lékem této skupiny na světě registrovaným americkou lékovou agenturou FDA), tak v Evropě registrována zcela nová hypolipidemika, která se v mnoha směrech odlišují od léků do současnosti podávaných. Přinášejí přitom další významný posun v léčbě poruch tukového metabolizmu i v preventivní kardiologii. Alirokumab je plně humánní monoklonální protilátka proti enzymu PCSK9 (proprotein konvertáza subtilizin/kexin typu 9). Enzym PCSK9 hraje významnou roli v metabolizmu LDL-cholesterolu tím, že ovlivňuje odbourávání, a posléze pak i počet a aktivitu LDL receptorů. Z klinického hlediska je podstatné, že se léky této skupiny podávají parenterálně, subkutánní injekcí. V případě Praluentu? je interval podání 1krát za 2 týdny. Dávka je potom 75 mg nebo 150 mg v injekci s obsahem 1 ml. Z klinického hlediska je významné především to, že alirokumab snižuje koncentraci LDL-cholesterolu o 50–60 %, snižuje hladinu lipoproteinu a o 25–30 %, pozitivně ovlivňuje i další složky lipidového metabolizmu a především má velmi pravděpodobně potenciál ke snížení kardiovaskulárního rizika. I když výsledky morbiditně-mortalitních studií jsou očekávány až v příštích letech, první analýzy vyznívají výrazně ve prospěch klinicky významného snižování KV-příhod. Alirokumab (Praluent?) je možno podávat v monoterapii (zejména u nemocných se statinovou intolerancí), zejména však bude podáván v kombinaci s dalšími hypolipidemiky (zejména statiny) u nemocných, u kterých se nedaří dosáhnout cílových hodnot. Klíčová slova: alirokumab – familiární hypercholesterolemie – hypercholesterolemie – hypolipidemika – Praluent?, At the present time there are novel hypolipidemics registered globally (alirocumab was the first drug of this group in the world registered by an American drug agency FDA) and in Europe, which in many ways differ from the medicines administered until now. They are bringing another advancement in the treatment of disorders of lipid metabolism and in preventive cardiology. Alirocumab is a fully human monoclonal antibody to PCSK-9 enzyme (proprotein convertase subtilisin kexin-9). PCSK-9 enzyme plays an important role in the metabolism of LDL-cholesterol through affecting the breakdown and eventually the amount and activity of LDL-receptors. From the clinical point of view it is essential that drugs from this group are administered parenterally, as a subcutaneous injection. In the case of Praluent? the interval between administration is two weeks. The dose is then 75 or 150mg in a 1ml injection. From the clinical point of view it is particularly important that alirocumab decreases LDL-C concentrations by 50–60%, it decreases Lp/a/ levels by 25–30%, and it also positively influences other components of lipid metabolism and, above all, is very likely to have a potential to decrease a cardiovascular risk. Although the resuIts of morbidity and mortality studies are expected in the coming years, initial analyses strongly indicate a clinically significant reduction of CV events. Alirocumab, Praluent can be administered as monotherapy (mainly to statin-intolerant patients), however it will be primarily administered in combination with the other hypolipidemic drugs (in particular statins) where the effort to reach target values has not succeeded. Key words: alirocumab – familial hypercholesterolemia – hypercholesterolemia – hypolipidemics – Praluent?, and Richard Češka
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
8634. Inhibice systému renin-angiotenzin-aldosteron u srdečního selhání aneb od obecného souhlasu (CONSENSUS) po vzorec myšlení (PARADIGM-HF)
- Creator:
- Vítovec, Jiří, Špinar, Jindřich, and Špinarová, Lenka
- Format:
- print, text, and regular print
- Type:
- model:article, article, Text, přehledy, and TEXT
- Subject:
- lidé, randomizované kontrolované studie jako téma, inhibitory ACE--terapeutické užití, blokátory receptoru 1 pro angiotenzin II--terapeutické užití, antagonisté mineralokortikoidních receptorů--terapeutické užití, amidy--terapeutické užití, fumaráty--terapeutické užití, pyridiny--terapeutické užití, thiazepiny--terapeutické užití, tetrazoly--terapeutické užití, aminobutyráty--terapeutické užití, srdeční selhání--farmakoterapie--mortalita, aliskiren, omapatrilát, LCZ 696, blokátory mineralokortikoidních receptorů, studie CHARM, studie HEAAL, studie SOLVD, studie ELITE, studie OVERTURE, studie RALES, and studie Val HeFT
- Language:
- Czech and English
- Description:
- Podán historický přehled mortalitních studií s inhibicí systému angiotenzin-aldosteron u nemocných s chronickým srdečním selháním. Od studie CONSENSUS po studii PARADIGM-HF se ukazuje, že zlatým standardem léčby jsou inhibitory ACE/blokátory AT1 receptorů pro angiotenzin II – sartany, spolu s blokátory mineralokortikoidních receptorů. Přímý blokátor reninu aliskiren a duální blokátor enalapril s inhibicí neprilysinu se ukázaly jako neúčinné, na druhé straně nový duální inhibitor valsartan + inhibitor neprilysinu LCZ 696 je novým nadějným léčebným přípravkem pro budoucnost léčby chronického srdečního selhání., An historical survey is presented of mortality trials on angiotensin-aldosteron system inhibition in patients with chronic heart failure. From the CONSENSUS trial up to the PARADIGM-HF trial, ACE inhibitors/angiotensin II receptor antagonists (AT1-blockers, ARBs, sartans), along with mineralocorticoid receptor blockers, have been the gold standard of treatment. Both direct renin blocker aliskiren and dual blocker enalapril + neprilysin proved ineffective; on the other hand, the new dual inhibitor valsartan + neprilysin LCZ 696 is a new and promising therapeutic agent for future treatment of chronic heart failure., and Jiří Vítovec, Jindřich Špinar, Lenka Špinarová
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
8635. Inhibin B, follicle stimulating hormone, luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relation to age and stage of puberty
- Creator:
- Martin Chada, Richard Průša, Jiří Bronský, Karel Kotaška, Kateřina Kotrčová, Markéta Pechová, and Ludmila Lisá
- Format:
- print, bez média, and svazek
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, dětství, puberta, childhood, puberty, male, inhibin B, 14, and 612
- Language:
- English
- Description:
- Inhibin B is a gonadal dimeric polypeptide hormone that regulates synthesis and secretion of follicle stimulating hormone (FSH) in a negative feedback loop. The aim of the present study was to determine changes in serum inhibin B, gonadotropins and testosterone concentrations during childhood and puberty in males. We studied the relationship between circulating inhibin B, gonadotropins and testosterone in serum of healthy boys during the first two years of life and then in pubertal development. Using a recently developed two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 78 healthy boys divided into eleven age groups from birth to the end of pubertal development. In addition, serum levels of gonadotropins and testosterone were measured. Serum inhibin B, gonadotropins and testosterone increased during the first months of postnatal life. A peak in serum inhibin B and gonadotropins concentrations was observed around 3-4 months of age. There was a significant positive correlation between serum inhibin B and gonadotropins and testosterone levels during the first 2 years of life. After this early increase, serum inhibin B, gonadotropins and testosterone levels decreased significantly and remained low until puberty followed by an increase beginning with the onset of puberty. Serum levels of inhibin B reached a peak at stage G3 of puberty. Around midpuberty, inhibin B lost its positive correlation with luteinizing hormone (LH) and testosterone from early puberty, and developed a strong negative correlation with FSH, which persisted into adulthood. We conclude that inhibin B plays a key role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis during male childhood and pubertal development. Inhibin B is a direct marker of the presence and function of Sertoli cells and appears to reflect testicular function in boys., M. Chada, R. Průša, J. Bronský, K. Kotaška, K. Šídlová, M. Pechová, L. Lisá., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
8636. Inhibin B, follicle stimulating hormone, luteinizing hormone, and estradiol and their relationship to the regulation of follicle development in girls during childhood and puberty
- Creator:
- Martin Chada, Richard Průša, Jiří Bronský, Markéta Pechová, Karel Kotaška, and Lidka Lisá
- Format:
- print, bez média, and svazek
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, dívky, dětství, puberta, girls, childhood, puberty, inhibin B, 14, and 612
- Language:
- English
- Description:
- a1_Inhibin B, produced by granulosa cells in the ovary, is a heterodimeric glycoprotein suppressing synthesis and secretion of the follicle stimulating hormone (FSH). The aim of the present study was to determine hormone profiles of inhibin B, FSH, luteinizing hormone (LH), and estradiol in girls during childhood and puberty and to evaluate whether inhibin B is a marker of follicle development. We examined the correlation between inhibin B and gonadotropins and estradiol during the first two years and across the pubertal development. Using a specific two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 53 healthy girls divided into 8 groups according to age. In addition, serum FSH, LH, and estradiol were measured by chemiluminescent immunoassay in all serum samples. A rise in serum levels of inhibin B (55.2±7.3 ng/l, mean ± S.E.M.) and FSH (1.78±0.26 UI/l), concomitant with a moderate increment of serum LH (0.36±0.09 UI/l) and estradiol (45.8±12.2 pmol/l) concentrations was observed during the first three months of life and declined to prepubertal concentrations thereafter. A strong positive correlation between inhibin B and FSH (r = 0.48, p<0.05), LH (r = 0.68, p<0.001) and estradiol (r = 0.59, p<0.01) was demonstrated during the first 2 years of life. A rise in serum levels of inhibin B, FSH, LH, and estradiol was found throughout puberty. Inhibin B had a strong positive correlation with FSH (stage I of puberty: r = 0.64, p<0.05; stage II of puberty: r = 0.86, p<0.01), LH (I: r = 0.61, p<0.05; II: r = 0.67, p<0.05), and estradiol (II: r = 0.62, p<0.05) in early puberty. From pubertal stage II, inhibin B lost this relationship to gonadotropins and estradiol. Serum inhibin B and FSH levels increased significantly during pubertal development, with the highest peak found in stage III of puberty (133.5±14.3 ng/l), and decreased thereafter., a2_In conclusion, inhibin B is produced in a specific pattern in response to gonadotropin stimulation and plays an important role in the regulation of the hypothalamic-pituitary-gonadal axis during childhood and puberty in girls. Inhibin B is involved in regulatory functions in developing follicles and seems to be a sensitive marker of ovarian follicle development., M. Chada, R. Průša, J. Bronský, M. Pechová, L. Lisá., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
8637. Inhibition of Beta-1 Receptor but not Vagotomy Can Abolish the L-NAME Evoked Bradycardia in Anesthetized Rat
- Creator:
- Vág, J., Hably, C., and Bartha, J.
- Format:
- print, bez média, and svazek
- Type:
- article, studie, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, fyziologie člověka, human physiology, Nitric oxide, Vagotomy, Metoprolol, Heart rate, 14, and 612
- Language:
- English
- Description:
- We reported previously that the nitric oxide synthesis inhibitor Nv-nitro-L-arginine methyl ester (L-NAME) decreases cardiac output. Several studies have shown that inhibition of nitric oxide synthesis decreases the heart rate. In the present study, we investigated the effect of a single bolus administration of L-NAME on blood pressure and heart rate monitored for one hour in anesthetized rats and the influence of vagotomy and b1-receptor blocker metoprolol on the L-NAME induced bradycardia. After L-NAME treatment, the blood pressure rose immediately after the injection of the drug (peak response in the third minute: +24 %, p<0.001) and fell to the control level in the 20th minute. The heart rate decreased immediately after L-NAME administration, the lowest value being reached in the 10th minute (-14 %, p<0.001). However, bradycardia was sustained even after the blood pressure had returned to the control level. Bilateral vagotomy failed to influence the negative chronotropic effect of L-NAME, but bradycardia was completely abolished by metoprolol pretreatment. We concluded that the bradycardia evoked by L-NAME is mainly due to the withdrawal of sympathetic tone upon the heart rate. However, the cause of sustained bradycardia after normalization of blood pressure cannot be elucidated., J. Vág, C. Hably, J. Bartha., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
8638. Inhibition of chiorophyll synthesis by selenium: involvement of lipoxygenase mediated lipid peroxidation and antioxidant enzymes
- Creator:
- Padmaja, K., Somasekharaiah, B.V., and Prasad, A.R.K.
- Format:
- Type:
- model:internalpart and TEXT
- Language:
- Multiple languages
- Description:
- Chlorophyll (Chl) biosynthesis intermediate compounds (like protoporphyrin-IX, Mg-protoporphyrin methyl ester and protochlorophyllide), Chl {a + h), heme, cytochrome P-450 (cyt P-450) and lipid peroxide levels as well as the activities of superoxide dismutase, catalase and lipoxygenase were studied in selenium treated mung beán seedlings. Chl (a -t- b) content and heme levels were decreased with a concomitant accumulation of all the three porphyrins studied. Se treatment enhanced the lipoxygenase activity and correspondingly increased lipid peroxide levels. Se inhibited both the antioxidant enzymes catalase and superoxide dismutase in a dose- dependent manner. However, cyt P-450 levels were enhanced under Se exposure. Hence the inhibitory effect of Se on Chl synthesis is not only by acting on constituent biosynthetic enzymes but also through lipoxygenase-mediated lipid peroxide levels and inhibition of antioxidant defence component systém.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
8639. Inhibition of maize leaf chlorophylls, carotenoids and gas exchange functions by cadmium
- Creator:
- Prasad, M.N.V.
- Format:
- Type:
- model:internalpart and TEXT
- Language:
- Multiple languages
- Description:
- The treatment of maize {Zea mays L.) seedlings (8-d-old) with 5 and 10 gM Cd^'*’ for 24 and 48 h caused a decrease in ffesh and dry mass, in the contents of chlorophylls and carotenoids, rates of net carbon dioxide uptake (Pyj) and transpiration (E), water use efficiency (Pyj/E = WUE) and stomatal conductance (gg).
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
8640. Inhibition of NO synthase activity in nervous tissue leads to decreased motor activity in the rat
- Creator:
- Lukáč Halčák, Oľga Pecháňová, Žigová, Z., Klemová, L., Novacký, M., and Iveta Bernátová
- Format:
- print, bez média, and svazek
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, oxid dusnatý, nitric oxide, L-NAME, nervous tissue, spontaneous behavior, habituation tasks, 14, and 612
- Language:
- English
- Description:
- The nitric oxide/cGMP system has been shown to play a crucial role in the mechanism of learning and memory. The aim of the present study was to investigate whether the inhibition of NO synthase in brain regions leads to alterations of spontaneous behavior in rats. Male Wistar rats were treated with NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at the dose of 40 mg/kg/day. After 4 weeks of L-NAME treatment, NO synthase activity was significantly decreased by 75 % in the cerebellum, by 71 % in the cerebral cortex and by 72 % in the thoracic spinal cord. Decreased NO synthase activity in the nervous tissue was associated with decreased motor horizontal and vertical activities as well as by lowered frequency of sniffing, cleaning and defecation. It is concluded that the inhibition of NO synthase activity has a suppressive effect on spontaneous behavior of rats., L. Halčák, O. Pecháňová, Z. Žigová, L. Klemová, M. Novacký, I. Bernátová., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public