Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol-lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection against myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff-perfused hearts of healthy control (C) and diabetic-hypercholesterolemic (D-H; streptozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium staining). Postischemic recovery of left ventricular developed pressure (LVDP) in animals with D-H was improved by simvastatin therapy (62.7+/-18.2 % of preischemic values vs. 30.3+/-5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperfusion. Likewise, simvastatin shortened the duration of ventricular tachycardia (10.2+/-8.1 s and 57.8+/-29.3 s in C and D-H vs. 143.6+/-28.6 s and 159.3+/-44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C. The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the improvement of contractile recovery and attenuation of lethal I/R injury in both, healthy and diseased individuals.

• MeSH
• cholesterol krev   MeSH
• experimentální diabetes mellitus komplikace   farmakoterapie   patologie   patofyziologie   MeSH
• hypercholesterolemie komplikace   farmakoterapie   patologie   patofyziologie   MeSH
• infarkt myokardu etiologie   patologie   patofyziologie   prevence a kontrola   MeSH
• ischemická choroba srdeční etiologie   patologie   patofyziologie   prevence a kontrola   MeSH
• kardiotonika farmakologie   MeSH
• komorový tlak (srdce) účinky léků   MeSH
• kontrakce myokardu účinky léků   MeSH
• krysa rodu Rattus MeSH
• myokard patologie   MeSH
• obnova funkce MeSH
• perfuze MeSH
• potkani Wistar MeSH
• simvastatin farmakologie   MeSH
• srdeční arytmie etiologie   patologie   patofyziologie   prevence a kontrola   MeSH
• statiny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholesterol MeSH
• kardiotonika MeSH
• simvastatin MeSH
• statiny MeSH

BACKGROUND AND OBJECTIVE: Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient's glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N-acetyl-beta-d glucosaminidase (NAG), creatinine level and creatinine clearance]. METHODS: We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft-Gault formula) and CyC (Grubb's formula). Seventy-one patients (mean age 12 years; range 4-28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U-creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy. RESULTS: Significant differences in the rate of U-NAG/U-creatinine were noted before and after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0.001), and CyC clearance showed a significant decrease (P < 0.001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased. CONCLUSION: We showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.

• MeSH
• acetylglukosaminidasa moč   MeSH
• amikacin aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• antibakteriální látky aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• cystatin C MeSH
• cystatiny krev   MeSH
• cystická fibróza krev   farmakoterapie   MeSH
• dítě MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace * MeSH
• intravenózní infuze MeSH
• kreatinin krev   moč   MeSH
• ledviny účinky léků   patologie   MeSH
• lidé MeSH
• mladiství MeSH
• monitorování léčiv MeSH
• předškolní dítě MeSH
• ROC křivka MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• srovnávací studie MeSH
• Názvy látek
• acetylglukosaminidasa MeSH
• amikacin MeSH
• antibakteriální látky MeSH
• biologické markery MeSH
• CST3 protein, human MeSH Prohlížeč
• cystatin C MeSH
• cystatiny MeSH
• kreatinin MeSH

OBJECTIVE: To evaluate the occurrence of mixed and unclassifiable vulvovaginitis (i.e. those, which fulfill the diagnostic criteria of several diagnostic units or no diagnostic unit) in symptomatic and asymptomatic women. TYPE OF STUDY: Prospective study. METHODS: In 412 women (115 of them asymptomatic) the authors established the diagnosis of vulvovaginitis on the basis of gynecological examination, pH, the amine test and microscopic examination according to Giemsa and Gram. RESULTS: Mycosis was diagnosed in 15.5% women (in 9,6% of asymptomatic ones), lactobacillosis in u 5.6% (in 7.0% of asymptomatic), anaerobic vaginosis in 10.7% (8.7% of asymptomatic), aerobic vaginitis in 7.7% women (4.3% of asymptomatic). U 15.0% mixed infections were diagnosed (in 61% asymptomatic). U 29.4% symptomatic women the diagnostic criteria were not fulfilled for any nosological unit. CONCLUSION: Vulvovaginal mycosis, lactobacillosis, anaerobic vaginosis, aerobic vaginosis were considered as dysmicrobia conditions. The authors demonstrated a high occurrence of more units ("clear" diagnoses to "mixed" diagnoses being in the ratio of 1.62:1). The authors also demonstrated a high occurrence of mixed infections in asymptomatic women (36.0%). On the contrary, in 29.4% of symptomatic women the diagnosis could not be established, the findings being "normal" or "unclassifiable".

• MeSH
• bakteriální vaginóza diagnóza   mikrobiologie   MeSH
• lidé MeSH
• mykózy diagnóza   mikrobiologie   MeSH
• vulvovaginitida diagnóza   mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

Rare diseases are defined as those affected less than five in every 10 000 person in European Union. The purpose of this paper is to present activities, which make possible to stimulate research development and marketing of appropriate medicine for tretment of rare disease, named "Orphan" medicinal products. EU "Orphan" medicinal products legislation which entered into force in April 2000 is described. Definition of "Orphan" medicinal products as well as the procedure of designation and placing the products into the Community register is presented. Those incentives to industry are described, which are already five years very well implemented oh the European level mostly on the pre-authorisation phase of "Orphan" medicinal products development, but also in the registration process as well as the post-authorisation phase. Finaly, the first twenty "Orphan" medicinal products, which have been given positive opinion in the Community for the grant of a marketing authorisation till April 2005 are mentioned in this work. The real availability of "Orphan" medicinal products in the particular EU member states is analysed.

• MeSH
• Evropská unie MeSH
• lidé MeSH
• schvalování léčiv MeSH
• výroba orphan drugs * MeSH
• vzácné nemoci farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

AIM OF THE STUDY: The evaluation of combined and miscellaneous vulvovaginal infections incidence and their treatment with combined vaginal products containing nifuratel and nystatin. DESIGN: Prospective study. SETTING: Gynecologic outpatient department LEVRET, Prague; Laboratories of Microbiology AescuLab, Prague. METHODS: 70 consecutive patients were examined with complaint of vaginal fluor and/or pruritus. We established macroscopic features of fluor, pH, amine test and mounts stained with Giemsa and Gram. We qualified the cases with more diagnostic criteria (mycosis, lactobacillosis, anaerobic vaginosis, aerobic vaginitis) as combined infection, those with no diagnostic criteria as miscellaneous. We treated all patients with vaginal tablets nystatin + nifuratel (Macmiror complex). We prescribed clotrimazol cream, if pruritus was present. We evaluated withdrawals of symptoms and relapses during 3 months after treatment. RESULTS: Combined infection was found in 21 patients from 70 (30%). The most frequent combination was that of mycosis and aerobic vaginitis (13/70, 18.6%) or mycosis and anaerobic vaginosis (4/70, 5.7%); 11 patients fulfilled criteria of no diagnosis. We concluded them as "miscelaneous". The treatment was successful in all cases, 10 women relapsed in 3 months. CONCLUSIONS: Combined vaginal infection findings are present very often (30%), likewise miscellaneous ones (15%) occur. The treatment of these women in successful with vaginal tablets with nystatin + nifuratel.

• MeSH
• antibakteriální látky aplikace a dávkování   MeSH
• antifungální látky aplikace a dávkování   MeSH
• antitrichomonádové látky aplikace a dávkování   MeSH
• aplikace intravaginální MeSH
• bakteriální vaginóza komplikace   farmakoterapie   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• kandidóza vulvovaginální komplikace   farmakoterapie   MeSH
• klotrimazol aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nifuratel MeSH
• nystatin aplikace a dávkování   MeSH
• trichomonádová vaginitida komplikace   farmakoterapie   MeSH
• vulvovaginitida farmakoterapie   mikrobiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• antitrichomonádové látky MeSH
• fixní kombinace léků MeSH
• klotrimazol MeSH
• nifuratel MeSH
• nystatin MeSH

Elevated lipid concentration is an important risk factor of cardiovascular diseases. Morbidity and mortality of these diseases are decreased by the reduction of lipid levels. Statins have significantly contributed to the improvement of cardiovascular diseases therapy and have been the most potent of the currently available lipid-modifying therapies so far. Intolerance, possible adverse events, and a failure to achieve target lipid levels may limit their use in some patients. This is also the reason for the development of new hypolipidemics. This paper deals with new potential hypolipidemic drugs which influence the fate of cholesterol in the organism from both physiological and pharmacological points of view. The new substances, such as cholesterol absorption inhibitors, ACAT inhibitors, MTP inhibitors, farnesoid receptor X antagonists, and SREBP-SCAP ligands represent the novel agents with potential hypolipidemic and anti-atherosclerotic activities.

• MeSH
• hyperlipidemie farmakoterapie   MeSH
• hypolipidemika terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• hypolipidemika MeSH

OBJECTIVE: The treatment of clinically uncertain conditions of vaginal discomforts with a mixed preparation of nifuratel + nystatin (Macmiror complex) and the relation of uncertain conditions to aerobic vaginitis. DESIGN: A prospective study. SETTING: Gynecology-Obstetrics Outpatient Department LEVRET Ltd., AescuLab Ltd., Laboratory of Microbiology, Prague. METHODS: 50 women with vaginal discomfort, causes of which had not been clarified by gynecological examination, determination of pH and the amine test, were examined by vaginal smears using microscopy. The results were evaluated in relation to aerobic vaginitis in a pure form or in combination with other nosological units. The authors also evaluated results of therapy by oral nifuratel (Macmiror tbl) 3 x 200 mg daily and a vaginal combined preparation containing nifuratel 500 mg + nystatin 200 kIU (Macmiror complex 500 glo vag) for the period of 7 days. RESULTS: In 50 women candida was demonstrated 24 times, presence of key cells 11 times, lactobacillus nine times with more than 50 in the field, six women were affected by aerobic vaginitis. In all these cases the pH was 4.8 or higher, leukocytes were significantly represented in all cases (> 15 in the field), as well as gram-negative bacteria and/or cocci (> 30 in the field), indicating a combined picture of mycosis, anaerobic vaginosis or lactobacillosis with aerobic vaginitis. The therapy was successful in all cases, the relapse of complaints during one month occurred in three cases. CONCLUSIONS: Aerobic vaginitis in a pure form or with anaerobic vaginosis, mycosis or lactobacillosis is frequently concealed under clinically uncertain pictures of vulvo-vaginal discomfort. The therapy by a combination of nifurated 3 x 200 mg orally together with the combined vaginal preparation nifuratel 500 mg + nystatin 200 kIU for the period of 7 days exerts high effect and a low number of relapses.

• MeSH
• bakteriální vaginóza diagnóza   farmakoterapie   mikrobiologie   MeSH
• lidé MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

Tissue can be paradoxically more severely damaged by reperfusion than by ischaemia itself (ischaemic-reperfusion injury--IRI). The mechanism of IRI has been intensively studied. Both the excessive formations of reactive oxygen radicals and calcium overload participate in the development of IRI. However, the significance of interaction between neutrophils and endothelial cells has been revealed recently. Imbalance of factors formed by endothelial cells and those formed by blood elements as well as the increased tendency to adhesion of neutrophils to the vascular endothelia during IRP has been proved. IRP effects on tissues can be pharmacologically influenced by: 1. anti-oxidative therapy, 2. substitution of cytoprotective factors formed in endothelial cells and blood elements, 3. inhibition of cytotoxic factors of endothelial cells and blood elements, 4. influencing the adhesion of neutrophils to the vascular endothelia, 5. administration of drugs acting by several of the above mentioned mechanisms. However, beside the application of the anti-oxidative therapy during the organ-transplant operations, only few of those approaches has been used in the clinical practice.

• MeSH
• lidé MeSH
• přivykání k ischémii MeSH
• reperfuzní poškození farmakoterapie   patofyziologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

Beta-blockers are being revived as effective, safe, reasonably priced and well-tolerated drugs. Differences in the pharmacodynamic and pharmacokinetic properties of beta-blockers now make it possible to select for the therapy of the individual diseases from a wide range of available beta-blockers the most effective drug with the minimal undesirable effects. It is made possible by the progress in the development of this ATS group and particularly by the third generation of these compounds. A proof of the prospects of these drugs is provided by their extended indications as the first-choice drugs (myocardial infarction) as well as the generally extended possibilities of their therapeutic use (therapy of heart failure).

• MeSH
• beta blokátory farmakokinetika   farmakologie   terapeutické užití   MeSH
• kardiovaskulární nemoci farmakoterapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• beta blokátory MeSH

The present experimental study reports the beneficial effects of newly synthetized substances IIIq and IIIb in vivo. These aryloxyaminopropanol drugs have been shown to antagonize the contraction caused by calcium comparable to verapamil and flunarizine in the model of the isolated guinea pig terminal ileum. Effects of substances on both the incidence of arrhythmias during ischemia and the reperfusion period and mortality were investigated in the rat model ischemia-reperfusion injury. We can conclude that compound IIIq in a dose of 10(-6) mol/kg is effective in reducing the incidence of reperfusion-induced arrhythmias. Substance IIIb (10(-6) mol/kg) administered before ischemia was not able to suppress arrhythmias in the rat model of myocardial infarction and reperfusion.

• MeSH
• antiarytmika terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• piperaziny terapeutické užití   MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu komplikace   prevence a kontrola   MeSH
• srdeční arytmie komplikace   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• antiarytmika MeSH
• piperaziny MeSH