Analysis of brown bullhead (Ameiurus nebulosus) bile by ultra performance liquid chromatography high-resolution mass spectrometry (UPLC/HRMS) revealed a series of bile acids similar to those found in humans. Accordingly, we chose this fish as a model organism to examine the metabolism of obeticholic acid, a bile acid used to treat a number of human liver diseases and the one that has the potential to occur as an environmental contaminant. The taurine and glycine conjugates of obeticholic acid and keto-obeticholic acid were identified, as well as the D-cysteinolic acid conjugate of obeticholic acid, likely a metabolite specific to fish. In addition, metabolites of obeticholic acid (sulphate and glucuronide) and several hydroxy-obeticholic acid derivatives were found, representing typical pathways of primary and secondary steroid metabolism. Brown bullhead exposed to obeticholic acid at a dose of 100 mg/kg gave no overt signs of distress or toxicity.
- MeSH
- Water Pollutants, Chemical pharmacokinetics toxicity MeSH
- Ecotoxicology methods MeSH
- Glycine metabolism MeSH
- Mass Spectrometry MeSH
- Ictaluridae metabolism MeSH
- Chenodeoxycholic Acid analogs & derivatives analysis pharmacokinetics toxicity MeSH
- Taurine metabolism MeSH
- Chromatography, High Pressure Liquid MeSH
- Bile chemistry MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
ÚVOD: V práci se zabýváme přehledným sdělením o poranění skeletu pánve s přidruženými zraněními. Zlomeniny pánevního kruhu jsou nejčastěji součástí vysokoenergetických poranění v rámci polytraumatu, s relativně nízkou frekvencí v populaci - 35/100 000 obyvatel za rok. Proto jsou směřována primárně do traumacenter s nepřetržitým provozem a dostupností všech potřebných specializací v rámci interdisciplinární péče. MATERIÁL A METODIKA: V intervalu posledních 3 let jsme ošetřovali 202 zlomenin pánve, z toho bylo operováno 73 pacientů. Vyšetření na Urgentním příjmu spočívá v klinickém vyšetření prostém AP rtg snímku pánve a hrudníku a sonografickém vyšetření břicha. Naložení pánevní svorky nahrazujeme v posledním roce pánevním pásem. V případě oběhově stabilního pacienta následuje vyšetření spirálním CT s nastavením timingu damage control surgery. Akutní operace je indikována u oběhově nestabilních pacientů z důvodu chir. ošetření krvácení repozicií a stabilizací pánve. V ojedinělých případech přistupujeme k packingu dutiny břišní malé pánve s dočasným uzávěrem zipem. Při poraněních orgánů dutiny břišní je nutná urgentní derivace moče a stolice a ošetření velkých cév. Multidisciplinární diagnostický a operační tým umožňuje ošetření orgánů dutiny břišní a skeletu v jedné době nebo ve zkráceném algoritmu DCS. Upřednostňujeme metody stabilní osteosyntézy úhlově stabilními dlahami a SI šrouby v jedné operační době. VÝSLEDKY: Z celkového počtu 202 zlomenin pánve bylo ošetřenou metodou ORIF 61, z toho 6 urgentní operací. Většina operovaných odpovídala klasifikaci AO skupina B a C. Současně byly ošetřeny poranění GIT 3, močového traktu 5, poranění velkých cév 2. Infekční komplikace se vyskytly 3, paresa n., ischiadiku 7 a hluboký zánět žil 5. Exitus letalis 4. ZÁVĚR: Za zásadní podmínky úspěšného řešení poranění pánve považujeme dobrou spolupráci se ZZS, spolehlivý komunikační systém nemocnice s nepřetržitým provozem všech zúčastněných odborností, eliminaci nežádoucích sekundárních transportů a operací a konstruktivní komunikaci multidisciplinární péče v rámci damage kontrol surgery.
INTRODUCTION: The point of this article is a synoptical overwiev of the pelvic skeleton injuries with its assciated injuries. Pelvic ring fractures are in most cases a result of high energy trauma in polytraumatic patients with a quite low incidence in the population – 35 (100 000 habitants) year. Therefore they're centered primarily into the Tramacentres with non-stop emergency service providing multidisciplinary medical care covering the full range of medical specializations needed. MATERIALS AND METHODS: We treated 202 pelvic skeleton fractures in the last three years, in 73 operative intervetion was necessary. The shock room investigation consists of the clinical evaluation, AP X-ray radiograph of pelvis and thorax as well as the abdomen US exploration. In the last year we prefer the pelvic compressive sling instead of aplying the pelvic C-clamp. The next step in case of haemodynamically stable patient is the whole-body CT scan setting up the damage control surgery timing simultaneously. In case of circulatory instability acute operative intervention is indicated for reasons of surgery bleeding management or pelvis reduction and stabilisation. In some rare cases packing of small pelvis is the last eventuality, closing the abdomen with Ethizip for second look. When abdominal viscera injuries are associated, urgent derivation of urine and feces is necessary as welll as major vessels ligation. Multidisciplinary diagnostic and operation team makes it possible to manage the visceral and skeletal injuries simultaneously or in the abbreviated algorithm of DCS. We prefer anglestable plating (LCP) methods and SI cannulated screws osteosynthesis at one intent. RESULTS: From the total number of 202 pelvic fractures 61 were treated by O.R.I.F. method, 6 of them as an urgent definitive satbilisation. Most of the operated fractures matched the AO classification group B and C. In 6 cases together with GIT visceral injury, 5 urinary tract injuries, 2 major vessels injury, 2 infectious complications, 7 paralyses of ischiadic nerve and 5 deep vein tromboses, 4 exitus letalis. CONCLUSION: Conditions that we consider to be crucial for successfull pelvic trauma management are the cooperation with emergency rescue service, a reliable communication system within the hospital with a continuous service of all the participating medical specialties, elimination of unwilling secondary transports and operations as well as constructive communication within the frame of multidisciplinary medical care in the algorithms of damage control surgery.
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Fractures, Bone diagnosis surgery classification MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Humans MeSH
- Interdisciplinary Communication MeSH
- Hospitals, Teaching MeSH
- Orthopedic Procedures methods utilization MeSH
- Pelvic Bones injuries MeSH
- Tomography, X-Ray Computed utilization MeSH
- Radiography methods MeSH
- Trauma Centers MeSH
- Thromboembolism drug therapy complications prevention & control MeSH
- Patient Care Team organization & administration trends MeSH
- Accidents classification MeSH
- Fracture Fixation, Internal methods utilization MeSH
- Check Tag
- Humans MeSH
The thalidomide tragedy stimulated an intense research in the etiology, prevention and treatment of congenital malformations. The Government requires that drugs and food additives be evaluated pre-clinically for toxicity, including developmental toxicity, before being marketed. The number of compounds which must be tested has increased dramatically with the continuous development of therapeutic, cosmetic and food additive chemicals. Such tests include: in vitro studies which can serve as efficient pre-screens to rank chemicals for further batteries of in vivo tests on pregnant animals. However, the safety of any drug would be determined only by a post-marketing epidemiological survey. Taking into account the altered susceptibility to different drugs in a pregnant individual, it could be said that administration of any drug during the first trimester is an experiment in human teratology.
- MeSH
- Abnormalities, Drug-Induced prevention & control MeSH
- Humans MeSH
- Fetal Death chemically induced MeSH
- Drug Evaluation, Preclinical MeSH
- Fetal Growth Retardation chemically induced MeSH
- Pregnancy MeSH
- Teratogens toxicity MeSH
- Teratology MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Bonded amalgam restorations have been studied extensively in vitro, but few long term clinical studies exist. The authors examined the clinical performance of bonded amalgam restorations after five years of clinical service an compared it with that of nonbonded amalgam restorations. METHODS: The authors placed 75 bonded and 62 nonbonded amalgam restorations in patients needing restorations. Most of the restorations were placed in conventional preparations; six bonded restorations were placed in nonretentive cavities. They were evaluated after a five-year period of clinical service by two trained dentists using a mirror and explorer and following modified U.S. Public Health Service criteria. RESULTS: Statistical analysis (via Fisher exact test) showed no significant differences between the two techniques when conventional preparations were used. Restorations in nonretentive preparations were successful during this period. CONCLUSIONS: Bonded and nonbonded amalgam restorations yielded similar results in conventional preparations after five years of clinical service. Bonded amalgam restorations were clinically successful in a limited number of nonretentive preparations over a five-year period. CLINICAL IMPLICATIONS: Bonded amalgam restorations can be used successfully in conventional preparations and possibly in nonretentive preparations as well, and can be expected to last at least five years.
- MeSH
- Dentin Sensitivity etiology MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Dental Restoration, Permanent methods adverse effects MeSH
- Dental Bonding * MeSH
- Treatment Outcome MeSH
- Dental Amalgam * MeSH
- Dental Caries etiology MeSH
- Dental Marginal Adaptation MeSH
- Dental Restoration Failure MeSH
- Check Tag
- Humans MeSH
- Publication type
- Controlled Clinical Trial MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
BACKGROUND & AIMS: Epicardial adipose tissue (EAT) is a source of a number of cytokines which could act in the pathogenesis of coronary artery disease (CAD). The potential relationship between known cardiovascular risk factors, such as smoking, dyslipidaemia or diabetes mellitus and EAT humoral signalling, has not been fully elucidated. Therefore, we designed and conducted a cross-sectional study to determine whether selected cardiovascular risk factors are linked to levels of cytokines in epicardial and subcutaneous adipose tissue (SAT). METHODS: Samples of SAT and EAT were collected from consecutive patients undergoing scheduled cardiac surgery. Tissue concentrations of tumour necrosis factor-ɑ (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein, leptin, and adiponectin were determined by ELISA. RESULTS: We enrolled 140 patients. TNF-α and IL-6 concentrations in EAT and SAT were significantly higher in current smokers (CS) than in never smokers (NS) and former smokers (FS). There were no differences between FS and NS. No other clinical variables were associated with cytokine concentrations in a regression analysis. CONCLUSIONS: Smoking was independently associated with higher TNF-α and IL-6 concentrations in EAT and SAT. A novel observation that pro-inflammatory cytokines are elevated in EAT in smokers could contribute to identify potential mechanisms involved in the pathogenesis of adverse effects of tobacco smoking. There were no differences between EAT cytokine production in NS and FS, which support the importance of smoking cessation for cardiovascular risk reduction.
- MeSH
- Interleukin-6 metabolism MeSH
- Smoking adverse effects metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Inflammation Mediators metabolism MeSH
- Smoking Cessation * MeSH
- Pericardium metabolism MeSH
- Subcutaneous Fat metabolism MeSH
- Smoking Prevention * MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Up-Regulation MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Cíl: Porovnání kvality zobrazení MR urografie s intravenózni vylučovací urografií, sonografií a scintigrafií močového traktu, prezentace MR urografie jako možné náhrady dosavadních vyšetření v předoperačním diagnostice anomálií horních močových cest. Metodika: Statickou MR urografií bylo vyšetřeno 51 pacientů ve věku 1 měsíc až 18 let se sonograficky zjištěnou dilatací horních močových cest, u 12 z nich byla provedena i dynamická MR studie ledvin. Magnetická urografie byla porovnána s vylučovací urografií, sonografií a dynamickou scintigrafií ledvin. V rámci komplexu předoperačních vyšetření byla hodnocena výtěžnost pro různé etáže močového traktu u pacientů do 2, 6,12 a 18 let. Výsledky: Z celkového počtu 36 hydronefroticky změněných ledvin byla 18x hodnocena jako přesnější magnetická urografie, 8x vylučovací urografie a l0x byla vyšetření na stejné úrovni. V zobrazení megaureterů byla MR urografie přesnější 7x, na stejné úrovni jako vylučovací urografie 6x a méně přesná 8x. Výsledky se lišily v jednotlivých věkových kategoriích. Sonografie dobře zobrazila ledvinu i dolní část močovodu, pro střední Část močovodu však nebyla dostatečná. Shodného průběhu exkrečních krivek u dynamické MR urografie a dynamické scintigrafie ledvin bylo dosaženo u 6 pacientů. Závěr: MR urografie je schopna přinést v jednom vyšetření informace o anatomii i funkci celého močového traktu, od vylučovací urografie se odlišuje schopností zobrazení a zhodnocení i hypofunkční části ledviny. Představuje možnost výrazné redukce dosavadních zatěžujících vyšetření.
Aims: To compare the quality of MR of urography with intravenous urography, sonography and scintigraphy of urinary tract, presentation of MR urography as a possible substitution of so far used examinations in preoperation diagnostics of anomalies in upper urinary tract. Methods: static MR urography was used to examine 51 patients at the age of one month to 18 years with dilatation of upper urinary tract detected by sonography. In 12 of them a dynamic MR study of the kidneys was also performed. Magnetic urography was compared with elimination urography, sonography and dynamic kidney scintigraphy. The detection rate was evaluated within the framework of the complex preoperation examinations for different stages of urinary tract in patients up to 2, 6,12 and 18 years, respectively. Results: in the total number of 36 kidneys, modified by hydronephrosis, magnetic urography was evaluated as more precise in 18 cases, elimination urography in eight and both examinations were considered equal in 10 cases. The imaging of megaureters by MR urography was more precise in 7 cases, elimination urography was at the same level six times and less precise in eight patients. The results differed in individual age categories. Sonography imaging of the kidney was good as well as for the lower portion of ureter but insufficient for the middle portion. The same course of excretion curves in dynamic excretion urography and dynamic scintigraphy of the kidney was reached in 6 patients. Conclusion: MR urography is capable to provide information on anatomy and function of the whole urinary tract in a single examination, being different from excretion urography by its ability of imaging and evaluating the hypofunctional part of the kidney. It represents a possibility to significantly reduce present examination which exerts a load upon the patient.
OBJECTIVE: The study objective was to evaluate the impact of a restrictive antibiotic policy, efficacy of inpatient therapeutic and prophylactic antibiotic regimens and susceptibility patterns of infecting bacteria in 2000-2004. SETTING: A 500-bed general hospital in the Czech Republic. METHOD: A retrospective computerized survey of antibiotic prescribing practices over a five-year period 2000-2004, using medical records and laboratory data from the hospital information system (HIS). MAIN OUTCOME MEASURE: Consumption of antibiotics expressed in defined daily doses (DDDs) and Euros per 1,000 bed days. Resistance to antibiotics, average length of hospital stay, rate of inpatients treated with antibiotics, number of nosocomial infections per 1,000 bed days, median length of hospital stay and total mortality. RESULTS: Due to a restrictive antibiotic policy implemented in 2002, the use of several antibiotics in 2003 was significantly reduced but the consumption of several other antibiotics rose in 2003. In comparison with 2001 the cost of antibiotic agents (in Euro per 1,000 inpatient days) fell significantly by 31% in 2003 Euro 969.07 vs. Euro 671.34). The hospital saved about Euro 29,288 after the first year of implementation of the new antibiotic policy. The use of restricted antibiotics increased by 8%; however, the expenditure decreased by 26%. For non-restricted antibiotics, the use and expenditure decreased by 71% and 41%, respectively. Consequently, a net reduction of 55% Euro 804.36 vs. Euro 359.36) was achieved. CONCLUSION: The intervention was effective in reducing the use and cost of antibiotics. The HIS is a helpful tool for observing and evaluating the impacts of the measures taken and can be used for assessment of pharmacotherapy outcomes.
- MeSH
- Anti-Bacterial Agents economics therapeutic use MeSH
- Bacterial Infections drug therapy MeSH
- Drug Resistance, Bacterial MeSH
- Length of Stay statistics & numerical data MeSH
- Financing, Organized MeSH
- Evaluation Studies as Topic MeSH
- Cross Infection epidemiology MeSH
- Cost Control MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Hospital Bed Capacity, 500 and over MeSH
- Hospitals, General MeSH
- Hospital Information Systems MeSH
- Retrospective Studies MeSH
- Practice Guidelines as Topic MeSH
- Drug Utilization statistics & numerical data MeSH
- Cost Savings MeSH
- Check Tag
- Humans MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND: In this study, the effect of novel taxane SB-T-1216 and paclitaxel on sensitive MDA-MB-435 and resistant NCI/ADR-RES human breast cancer cells was compared. MATERIALS AND METHODS: Cell growth and survival were evaluated after 96-hour incubation with tested concentrations of taxanes. The effect on the formation of microtubule bundles was assessed employing fluorescence microscopy and on the cell cycle employing flow cytometric analysis. The activity of caspases was assessed employing commercial colorimetric kits. RESULTS: The IC(50) (concentration resulting in 50% of living cells in comparison with the control) of SB-T-1216 in sensitive cells was 0.6 nM versus 1 nM for paclitaxel. However, the IC(50) of SB-T-1216 in resistant cells was 1.8 nM versus 300 nM for paclitaxel. Both SB-T-1216 and paclitaxel at death-inducing concentrations induced the formation of microtubule bundles in sensitive as well as resistant cells. Cell death induced in sensitive and resistant cells by paclitaxel was associated with the accumulation of cells in the G(2)/M phase. On the contrary, cell death induced by SB-T-1216 took place without the accumulation of cells in the G(2)/M phase but with a decreased number of G(1) cells and the accumulation of hypodiploid cells. Both SB-T-1216 and paclitaxel activated caspase-3, caspase-9, caspase-2 and caspase-8 in sensitive as well as resistant cells. CONCLUSION: Cell death induced by both paclitaxel and novel taxane SB-T-1216 in breast cancer cells is associated with caspase activation and with the formation of interphase microtubule bundles. Novel taxane SB-T-1216, but not paclitaxel, seems to be capable of inducing cell death without the accumulation of cells in the G(2)/M phase.
- MeSH
- Antibiotics, Antineoplastic pharmacology MeSH
- Antineoplastic Agents, Phytogenic pharmacology MeSH
- Apoptosis drug effects MeSH
- Cell Division drug effects MeSH
- Drug Resistance, Neoplasm MeSH
- Doxorubicin pharmacology MeSH
- Microscopy, Fluorescence MeSH
- G1 Phase drug effects MeSH
- G2 Phase drug effects MeSH
- Caspase 2 metabolism MeSH
- Caspase 3 metabolism MeSH
- Caspase 8 metabolism MeSH
- Caspase 9 metabolism MeSH
- Humans MeSH
- Microtubules drug effects MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms drug therapy metabolism pathology MeSH
- Paclitaxel pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Taxoids pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Comparative Study MeSH
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that can trigger apoptosis in many types of human cancer cells via engagement of its two pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). TRAIL can also activate several other signaling pathways such as activation of stress kinases, canonical NF-κB signaling and necroptosis. Though both receptors are ubiquitously expressed, their relative participation in TRAIL-induced signaling is still largely unknown. To analyze TRAIL receptor-specific signaling, we prepared Strep-tagged, trimerized variants of recombinant human TRAIL with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, we examined the contribution of individual pro-apoptotic receptors to TRAIL-induced signaling pathways. We found that in TRAIL-resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeds comparably via both DR4- and DR5-activated signaling. TRAIL-induced apoptosis, enhanced by the inhibitor of the Bcl-2 family ABT-737, or by the translation inhibitor homoharringtonine, proceeded in both cell lines predominantly via the DR5 receptor. ShRNA-mediated downregulation of DR4 or DR5 receptors in HT-29 cells also pointed to a stronger contribution of DR5 in TRAIL-induced apoptosis. In contrast to apoptosis, necroptotic signaling was activated similarly by both DR4- or DR5-specific ligands. Activation of auxiliary signaling pathways involving NF-κB or stress kinases proceeded under apoptotic conditions mainly in a DR5-dependent manner, while these signaling pathways were during necroptosis similarly activated by either of these ligands. Our study provides the first systematic insight into DR4-/DR5-specific signaling in colorectal and pancreatic cancer cells.
- MeSH
- Apoptosis genetics MeSH
- HT29 Cells MeSH
- Caspase 8 genetics MeSH
- Colorectal Neoplasms genetics pathology MeSH
- Humans MeSH
- RNA, Small Interfering MeSH
- Pancreatic Neoplasms genetics pathology MeSH
- Necrosis genetics pathology MeSH
- NF-kappa B genetics MeSH
- Pancreas metabolism pathology MeSH
- Cell Proliferation genetics MeSH
- TNF-Related Apoptosis-Inducing Ligand genetics MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Signal Transduction genetics MeSH
- Receptors, TNF-Related Apoptosis-Inducing Ligand genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
