BACKGROUND: Unexpected accidental intoxication by uncommon industrial substances is a rare, but challenging and perilous event. To our best knowledge, this is the first reported case of 3,4',5,6'-tetra-tert-butylbiphenyl-2,3'-diol intoxication. CASE REPORT: A 20-year-old man was referred to the Department of Emergency Medicine after seven days of nausea and vomiting triggered by drinking mead. Very high doses of 3,4',5,6'-tetra-tert-butylbiphenyl-2,3'-diol were detected in mead, blood, and urine samples. To prove the intoxication, gas chromatography - ion trap was performed. Symptoms of intoxication persisted for two weeks without significant organ damage. The case report illustrates the need for a multistep approach, focused mainly on the analysis of possible sources of intoxication.
- MeSH
- chromatografie plynová MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- nauzea * MeSH
- zvracení * chemicky indukované MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Metody: Byly analyzovány výsledky klinických a laboratorních vyšetření a data z pacientského dotazníku. Součástí bylo subjektivní hodnocení adherence (A) pacientem a lékařem. Referenční metodou pro průkaz NA bylo vyšetření sérových hladin léků (SHL). Výsledky: Bylo zařazeno 81 pacientů. Stanovením SHL byla NA zjištěna u 25 %. Všichni pacienti uvedli, že léky užívají správně, vynechání některé dávky v týdnu připustilo 18 % A a 25 % NA (p = 0,53). Lékař předpokládal NA správně u 40 % NA a chybně u 10 % A. Byl trend k častější NA u žen (p = 0,055), méně častá byla u pacientů z vesnice nebo malého města (p = 0,031). NA měli vyšší systolický (137 ± 13 vs. 124 ± 15 mmHg, p = 0,001) i diastolický (83 ± 11 vs. 75 ± 9 mmHg, p = 0,002) krevní tlak. Byl trend k vyšší tepové frekvenci u NA (83 ± 18 vs. 73 ± 13, p = 0,052), v podskupině léčených betablokátory byl rozdíl signifikantní (94 ± 19 vs. 73±12, p < 0,001). Adherentní nesignifikantně lépe hodnotili svůj zdravotní stav (p = 0,052). V ostatních parametrech nebyl nalezen rozdíl. Závěr: NA můžeme předpokládat u léčených pacientů s přetrvávajícím vyšším TK a u pacientů s vyšší TF při léčbě betablokátory. NA lze potvrdit stanovením SHL.
Methods: Routine examination results, patient questionnaires as well as adherence (A) assessment by both the patient and physician were analyzed. Serum drug levels (SDLs) were used as a reference method. Results: Eighty-one patients were enrolled. Using SDL, non-adherence was shown in 25 %. All patients reported to have taken their drugs properly. Omission of a dose a week was admitted by 18 % of A and 25 % of NA patients (p = 0.53). The physician correctly assumed NA in 40 % of NA patients, but incorrectly in 10 % of A. There was a trend among women to be more non-adherent (p = 0.055) while in patients from a village or small town lower NA (p = 0.031) was observed. The systolic (137 ± 13 vs. 124 ± 15 mm Hg, p = 0.001) and diastolic (83 ± 11 vs. 75 ± 9 mm Hg, p = 0.002) blood pressure values were higher in NA. There was a trend towards a higher heart rate (83 ± 18 vs. 73 ± 13, p = 0.052) in NA, with a significant difference in patients treated with beta-blockers (94 ± 19 vs. 73 ± 12, p < 0.001). Adherent patients rated their health status better (p = 0.052). No differences were found in the other parameters. Conclusion: NA may be predicted in persistent high blood pressure and in high heart rate despite beta-blockers. NA can be confirmed by SDL assessment.
- MeSH
- adherence k farmakoterapii * MeSH
- antihypertenziva krev MeSH
- chromatografie kapalinová MeSH
- chronická nemoc * MeSH
- farmakovigilance MeSH
- hmotnostní spektrometrie MeSH
- interpretace statistických dat MeSH
- krevní tlak účinky léků MeSH
- lidé MeSH
- pozorovací studie jako téma MeSH
- prospektivní studie MeSH
- průzkumy a dotazníky MeSH
- srdeční selhání * diagnóza MeSH
- Check Tag
- lidé MeSH
BACKGROUND: The aim of our study was to evaluate the prevalence of drug non-adherence in stable chronic heart failure (CHF) patients using serum drug levels (SDL) assessment. METHODS: CHF patients were prospectively enrolled during scheduled outpatient visit. Except standard procedures an unanticipated blood sampling for the SDL assessment was obtained. Analysis was focused on the prescribed heart failure and antihypertensive medication and was performed by liquid chromatography coupled with mass spectrometry. The patient was labelled as non-adherent if at least one of drugs assessed was not found in the serum. In the first half of patients multiple SDL have been evaluated during the follow-up. RESULTS: Eighty one patients were enrolled. The non-adherence was proven in twenty of them (25%). In the subgroup of thirty eight patients with multiple SDL evaluation the non-adherence raised significantly with increasing number of visits assessed together (21% for single visit, 29% for two of three visits assessed together and 34% for all three visits evaluated together, all p < 0.001). CONCLUSION: The non-adherence was proven in significant part of stable CHF patients using SDL assessment. This method seems to be reliable and effective and should be a part of clinical assessment in selected patients with CHF.
- MeSH
- adherence k farmakoterapii psychologie statistika a číselné údaje MeSH
- antihypertenziva krev terapeutické užití MeSH
- chromatografie kapalinová MeSH
- chronická nemoc * psychologie MeSH
- hmotnostní spektrometrie MeSH
- kardiotonika krev terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- srdeční selhání farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
The objective of this study was to elucidate the pharmacokinetics and metabolite formation of newly developed non-selective AChE/BChE 7-MEOTA-donepezil-like inhibitors for potential therapeutic use in Alzheimer's disease (AD) patients. The chemical structures of metabolites were defined during incubation with human liver microsomes, and subsequently, the metabolization was verified in in vivo study. In vitro metabolic profiling revealed the formation of nine major metabolites in the case of PC-37 and eight metabolites of PC-48. Hydroxylation and the enzymatic hydrolysis of bonds close to the piperazine ring appeared to be the principal metabolic pathways in vitro. Of these metabolites, M1-M7 of PC-37 and M1-M6 of PC-48 were confirmed under in vivo conditions. Pilot pharmacokinetic experiments in rats were focused on the absorption, distribution and elimination of these compounds. Absorption after i.m. application was relatively fast; the bioavailability expressed as AUCtotal was 28179 ± 4691 min.ng/mL for PC-37 and 23374 ± 4045 min.ng/mL for PC-48. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. The maximal brain concentrations are approximately two times higher than the plasma concentrations. The relatively high brain concentrations persisted throughout the experiment until 24 hr after application. Elimination via the kidneys (urine) significantly exceeded elimination via the liver (bile). All these characteristics are crucial for new candidates intended for AD treatment. The principle metabolic pathways that were verified in the in vivo study do not show any evidence for formation of extremely toxic metabolites, but this needs to be confirmed by further studies.
- MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- biologická dostupnost MeSH
- cholinesterasové inhibitory chemická syntéza metabolismus farmakokinetika terapeutické užití MeSH
- hydrolýza MeSH
- hydroxylace MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- metabolické sítě a dráhy MeSH
- mozek účinky léků MeSH
- pilotní projekty MeSH
- piperaziny chemická syntéza metabolismus farmakokinetika terapeutické užití MeSH
- potkani Wistar MeSH
- takrin analogy a deriváty chemická syntéza metabolismus farmakokinetika terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for the first time in 2001. The aim of the current multicenter prospective study was to evaluate dyspepsia using the same methods in a representative sample of general unselected population from the same geographical areas 10 years later. PARTICIPANTS AND METHODS: A total of 38 147 individuals comprised the general population for a random two-step selection process. A total of 1836 participants (863 males and 973 females; aged 5-98 years) took part in the questionnaire-based study. Helicobacter pylori status was investigated in all participants by means of C-urea breath test. RESULTS: The overall prevalence of dyspepsia was 2.6% among children and adolescents aged 5-17 years and 16.0% among adults aged 18-98 years. We did not detect any statistically significant sex differences in the prevalence of total dyspepsia or its subtypes. Overall, 2.4% of H. pylori-negative children and adolescents aged less than 18 years reported dyspepsia, and 16.8% of H. pylori-negative adults reported it. Among H. pylori-positive children and adolescents and adults, dyspepsia was present in 8.3 and 15.8%, respectively. Type A dyspepsia (as the only long-lasting symptom) was statistically significantly associated with H. pylori status among children and adolescents. Among adults aged 18 years or older, we noted a lower prevalence of dyspepsia in adults with elementary education compared with university education. Current use of antibiotics was associated with an increased prevalence of dyspepsia in adults. CONCLUSION: Despite the substantial decrease of H. pylori infection in the Czech Republic over the past 10 years, the prevalence and sociodemographic determinants of uninvestigated dyspepsia did not change significantly.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- časové faktory MeSH
- charakteristiky bydlení MeSH
- dítě MeSH
- dospělí MeSH
- dyspepsie diagnóza epidemiologie mikrobiologie MeSH
- Helicobacter pylori izolace a purifikace MeSH
- infekce vyvolané Helicobacter pylori diagnóza epidemiologie mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- prevalence MeSH
- prognóza MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- rozložení podle pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sexuální faktory MeSH
- socioekonomické faktory * MeSH
- stupeň vzdělání MeSH
- věkové faktory MeSH
- věkové rozložení MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). OBJECTIVE: To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). METHODS: The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. RESULTS: Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). CONCLUSION: Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.
- MeSH
- aplikace kožní MeSH
- biologické markery krev moč MeSH
- časové faktory MeSH
- celotělové ozáření MeSH
- chronická nemoc MeSH
- dehet uhelný aplikace a dávkování škodlivé účinky MeSH
- dospělí MeSH
- keratolytika aplikace a dávkování škodlivé účinky MeSH
- kombinovaná terapie MeSH
- kouření škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- oxidační stres účinky léků účinky záření MeSH
- polycyklické aromatické uhlovodíky aplikace a dávkování škodlivé účinky MeSH
- poškození DNA MeSH
- psoriáza diagnóza metabolismus terapie MeSH
- pyreny moč MeSH
- senioři MeSH
- stabilita RNA účinky léků účinky záření MeSH
- stárnutí kůže účinky léků účinky záření MeSH
- terapie ultrafialovými paprsky škodlivé účinky metody MeSH
- vitamin D analogy a deriváty krev MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH