We describe the internal structure, spatial organization and dynamic formation of coronary artery thrombi from ST-segment elevation myocardial infarction patients. Scanning electron microscopy (SEM) revealed significant differences among four groups of patients (<2 hours; 2-6 hours; 6-12 hours, and >12 hours) related to the time of ischemia. Coronary artery thrombi from patients presenting less than 2 hours after the infarction were almost entirely composed of platelets, with small amounts of fibrin and red blood cells. In contrast, thrombi from late presenters (>12 hours) consisted of mainly platelets at the distal end, where clotting was initiated, with almost no platelets at the proximal end, while the red blood cell content went from low at the initiating end to more than 90% at the proximal end. Furthermore, fibrin was present mainly on the outside of the thrombi and older thrombi contained thicker fibers. The red blood cells in late thrombi were compressed to a close-packed, tessellated array of polyhedral structures, called polyhedrocytes. Moreover, there was redistribution from the originally homogeneous composition to fibrin and platelets to the outside, with polyhedrocytes on the interior. The presence of polyhedrocytes and the redistribution of components are signs of in vivo clot contraction (or retraction). These results suggest why later thrombi are resistant to fibrinolytic agents and other treatment modalities, since the close-packed polyhedrocytes form a nearly impermeable seal. Furthermore, it is of particular clinical significance that these findings suggest specific disparate therapies that will be most effective at different stages of thrombus development.
- MeSH
- čas zasáhnout při rozvinutí nemoci MeSH
- časové faktory MeSH
- erytrocyty patologie MeSH
- fibrin analýza MeSH
- fibrinolytika * aplikace a dávkování škodlivé účinky MeSH
- hemokoagulace účinky léků fyziologie MeSH
- infarkt myokardu s elevacemi ST úseků * etiologie terapie MeSH
- koronární trombóza * diagnostické zobrazování farmakoterapie metabolismus patologie MeSH
- léková rezistence fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopie elektronová rastrovací metody MeSH
- trombektomie metody MeSH
- trombocyty patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Drug resistance has now become a serious concern in the domain of microbial infection. Bacteria are becoming smarter by displaying a variety of mechanisms during drug resistance. It is not only helping bacteria to adapt nicely in adverse environment but it also makes a smart system for better availability of nutritional status for microorganisms. In this domain, pathogenic bacteria are extensively studied and their mechanism for drug resistance is well explored. The common modes in bacterial resistance include degradation of antibiotics by enzymes, antibiotic target modification or inactivation by enzymatic actions, complete replacement of antibiotic targets, quorum sensing (QS) mechanism, and efflux pump-based extrusion of antibiotics. In this review, various mechanisms of drug resistance in bacteria have been highlighted with giving the importance of efflux pumps. This can be explored as a knowledge source for the management of a variety of bacterial infections, related disease and vibrant clue for next-generation drug development.
Vznik nádorové rezistence na cílenou léčbu představuje významný zdravotnický problém. Překonání těchto mechanismů by vedlo k prodloužení účinku této formy léčby, která vyniká výrazně vyšším procentem terapeutických odpovědí než imunoterapie. Klíčem k vývoji nových léčiv, která by potencovala účinek BRAF a MEK inhibitorů, je podrobné zmapování mechanismů rezistence. Tato práce poukazuje na některé mechanismy epigenetické, genetické a působení nádorového mikroprostředí. Poukazuje i na vliv imunitního systému, který nabízí jednu z cest, jak účinek cílené terapie potencovat.
- Klíčová slova
- inhibitory BRAF, inhibitory MEK,
- MeSH
- imunomodulace MeSH
- léková rezistence * fyziologie genetika imunologie MeSH
- lidé MeSH
- melanom * farmakoterapie imunologie patofyziologie MeSH
- mezibuněčné signální peptidy a proteiny fyziologie MeSH
- mutace genetika MeSH
- nádorové mikroprostředí imunologie účinky léků MeSH
- proteinkinasy fyziologie účinky léků MeSH
- proteiny genetika MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
The emergence of artemisinin (ART) resistance in Plasmodium falciparum intra-erythrocytic parasites has led to increasing treatment failure rates with first-line ART-based combination therapies in Southeast Asia. Decreased parasite susceptibility is caused by K13 mutations, which are associated clinically with delayed parasite clearance in patients and in vitro with an enhanced ability of ring-stage parasites to survive brief exposure to the active ART metabolite dihydroartemisinin. Herein, we describe a panel of K13-specific monoclonal antibodies and gene-edited parasite lines co-expressing epitope-tagged versions of K13 in trans. By applying an analytical quantitative imaging pipeline, we localize K13 to the parasite endoplasmic reticulum, Rab-positive vesicles, and sites adjacent to cytostomes. These latter structures form at the parasite plasma membrane and traffic hemoglobin to the digestive vacuole wherein artemisinin-activating heme moieties are released. We also provide evidence of K13 partially localizing near the parasite mitochondria upon treatment with dihydroartemisinin. Immunoprecipitation data generated with K13-specific monoclonal antibodies identify multiple putative K13-associated proteins, including endoplasmic reticulum-resident molecules, mitochondrial proteins, and Rab GTPases, in both K13 mutant and wild-type isogenic lines. We also find that mutant K13-mediated resistance is reversed upon co-expression of wild-type or mutant K13. These data help define the biological properties of K13 and its role in mediating P. falciparum resistance to ART treatment.
- MeSH
- antimalarika farmakologie MeSH
- artemisininy farmakologie MeSH
- léková rezistence genetika fyziologie MeSH
- lidé MeSH
- mutace MeSH
- Plasmodium falciparum genetika metabolismus MeSH
- protozoální proteiny metabolismus MeSH
- tropická malárie parazitologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
OBJECTIVES: Little is known about the relation between severity of panic disorder, adverse events in childhood, dissociation, self-stigma and comorbid personality disorders. The aim of this study is to look for the intercorrelations between these factors. METHOD: The study explores the relation between clinical, demographic and social factors in panic disorder using cross sectional design. The inpatients with pharmacoresistant panic disorder with and without agoraphobia were included in the study. Participants were also assessed for comorbidity with other anxiety or personality disorder. The Clinical Global Impression (CGI), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), Dissociative Experiences Scale (DES), Internalized Stigma of Mental Illness (ISMI), Childhood Trauma Questionnaire-Short Form (CTQ-SF), Panic Disorder Severity Scale (PDSS) and demographic data were used as measurement tools. RESULTS: A total of 142 pharmacoresistant patients with panic disorder with or without agoraphobia were admitted for 6-week cognitive behavioral therapy inpatient program in psychotherapeutic department between November 2015 and July 2019. One hundred and five inpatients (33 males and 72 females) with mean age 37.8 + 12.1 years were included in the study. Sixty-nine patients suffer from additional comorbid anxiety disorder and 43 had comorbid personality disorder.
- MeSH
- demografie MeSH
- disociační poruchy epidemiologie psychologie MeSH
- dítě MeSH
- dospělí MeSH
- komorbidita MeSH
- léková rezistence fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nepříznivé zkušenosti z dětství statistika a číselné údaje MeSH
- panická porucha komplikace farmakoterapie epidemiologie psychologie MeSH
- poruchy osobnosti komplikace epidemiologie MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- psychiatrické posuzovací škály MeSH
- psychometrie MeSH
- sebepojetí * MeSH
- společenské stigma * MeSH
- stupeň závažnosti nemoci MeSH
- vývoj dítěte fyziologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: A combination of antidepressants with the cognitive-behavioural therapy showed effectiveness in treatment-resistant patients with panic disorder. This prospective study intended to establish how childhood adverse experiences, self-stigma, dissociation, and severity of psychopathology influence the effectiveness of combined cognitive-behavioural therapy and pharmacotherapy in patients with treatment-resistant panic disorder. METHODS: One hundred and ten patients were included into the study and one hundred five subjects finished the study. After admission, the subjects were assessed during the first two days of hospitalization. Rating scales were administered before the beginning of the cognitive behavioural therapy (measurement-1) and at the end of the treatment which was after six weeks (measurement-2). Patients with panic disorder were treated using a combination of group cognitive-behavioural therapy and antidepressants. The usual antidepressant dosage range was used. Before admission to intensive cognitive behavioural therapy program, the patients were unsuccessfully treated by antidepressants for minimum 3 months, which defined them as pharmacoresistant. RESULTS: Hospitalized pharmacoresistant patients with panic disorder improved significantly throughout the 6-week intensive CBT program in all measurements that assessed the overall severity of the disorder, the degree of general anxiety and depression and the severity of specific symptoms of panic disorder and agoraphobia. The rate of improvement was negatively related to sexual abuse in childhood, presence of comorbid personality disorder, and positively with the severity of the disorder at the beginning, and the level of self-stigma at the beginning of treatment. Improvement in symptoms correlates significantly with decreasing of dissociation during the treatment.severity of depressive symptoms. The earlier development of the disorder is linked to higher score in childhood adverse events, higher level of dissociation and pathological dissociation, and higher level of self-stigma. CONCLUSIONS: Our prospective study discovers importance of the role of adverse childhood experiences, self-stigma, dissociation and comorbid personality disorder in effectiveness of combined cognitive-behavioural therapy and pharmacotherapy treatment in patients with treatment-resistant panic disorder.
- MeSH
- antidepresiva terapeutické užití MeSH
- disociační poruchy komplikace epidemiologie terapie MeSH
- dítě MeSH
- dospělí MeSH
- hospitalizace statistika a číselné údaje MeSH
- hospitalizovaní pacienti MeSH
- kognitivně behaviorální terapie * MeSH
- kombinovaná terapie MeSH
- komorbidita MeSH
- léková rezistence * fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nepříznivé zkušenosti z dětství * statistika a číselné údaje MeSH
- panická porucha diagnóza epidemiologie psychologie terapie MeSH
- poruchy osobnosti epidemiologie terapie MeSH
- sebepojetí MeSH
- společenské stigma MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- vývoj dítěte fyziologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- MeSH
- antibakteriální látky * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- antibiotická rezistence * fyziologie imunologie účinky léků MeSH
- Crohnova nemoc diagnóza farmakoterapie komplikace MeSH
- fluorochinolony aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- idiopatické střevní záněty * diagnóza imunologie komplikace MeSH
- léková rezistence fyziologie imunologie účinky léků MeSH
- lidé MeSH
- metaanalýza jako téma MeSH
- metronidazol aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- nežádoucí účinky léčiv komplikace prevence a kontrola MeSH
- statistika jako téma MeSH
- střevní mikroflóra fyziologie imunologie účinky léků MeSH
- ulcerózní kolitida diagnóza farmakoterapie komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance. We have attempted to address following questions: 1) What does stay behind differences among patients as to their response to the (anti)steroid treatment? 2) Why do various tissues/cells respond differently to the same steroid hormone though they contain the same receptors? 3) Are such differences genetically dependent? The main attention was devoted to glucocorticoids as the most frequently used steroid therapeutics. Further, androgen insensitivity is discussed with a particular attention to acquired resistance to androgen deprivation therapy of prostate cancer. Finally the potential causes are outlined of breast and related cancer(s) resistance to antiestrogen therapy.
- MeSH
- androgenní receptory metabolismus MeSH
- antagonisté hormonů metabolismus farmakologie terapeutické užití MeSH
- glukokortikoidy metabolismus farmakologie terapeutické užití MeSH
- léková rezistence účinky léků fyziologie MeSH
- lidé MeSH
- nádory prostaty farmakoterapie metabolismus MeSH
- nádory prsu farmakoterapie metabolismus MeSH
- pohlavní steroidní hormony metabolismus farmakologie terapeutické užití MeSH
- steroidní receptory metabolismus MeSH
- steroidy metabolismus farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Práce shrnuje základní poznatky o výskytu, etiopatogenezi, diagnostice, klinickém obrazu, průběhu a léčbě schizofrenní poruchy. Nejvíce pozornosti je věnováno léčbě. Základem zůstává farmakoterapie antipsychotiky. Jsou rozebírány možnosti individualizované léčby z hlediska dominujících příznaků, individuální snášenlivosti, nežádoucích účinků a preferencí nemocného. Důraz je kladen na optimalizaci farmakoterapie, která zahrnuje terapeutické monitorování léku a perspektivně farmakogenetické testy. Péče o nemocné se závažnými psychickými chorobami a humanizace jejich léčby se stává prioritou Evropské unie. V této souvislosti je zmíněna i reforma psychiatrické péče.
The paper summarizes the basic knowledge about occurrence, aethiopathogenesis, diagnosis, clinical picture and treatment of schizophrenia. Attention is devoted especially to its treatment. Pharmacotherapy remains the basis of schizophrenia treatment. Possibilities of individualized treatment are discussed, as guided by prevalent symptoms, individual tolerability a patient preferences. Optimization of pharmacotherapy is stressed out, which includes therapeutic drug monitoring and prospectively pharmacogenetic testing as well. The care for patients with severe mental illnesses and humanization of their treatment are becoming a priority in the European Union. A reform of psychiatric care is mentioned in this context.
- MeSH
- adherence k farmakoterapii psychologie MeSH
- antagonisté dopaminu farmakologie škodlivé účinky terapeutické užití MeSH
- antagonisté serotoninu farmakologie škodlivé účinky terapeutické užití MeSH
- antipsychotika farmakologie škodlivé účinky terapeutické užití MeSH
- behaviorální symptomy MeSH
- diferenciální diagnóza MeSH
- komplikace těhotenství etiologie farmakoterapie MeSH
- léková rezistence fyziologie genetika MeSH
- lékové interakce MeSH
- lidé MeSH
- monitorování léčiv trendy MeSH
- prognóza MeSH
- psychoterapie metody MeSH
- rozvrh dávkování léků MeSH
- schizofrenie * diagnóza epidemiologie farmakoterapie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Klíčová slova
- Prestarium Neo Combi,
- MeSH
- antihypertenziva * aplikace a dávkování farmakologie terapeutické užití MeSH
- chybná diagnóza * škodlivé účinky MeSH
- dospělí MeSH
- farmakoterapie metody MeSH
- fixní kombinace léků MeSH
- hyperaldosteronismus diagnóza farmakoterapie chirurgie komplikace MeSH
- hypertenze * diagnóza farmakoterapie prevence a kontrola terapie MeSH
- klinické laboratorní techniky využití MeSH
- krevní tlak fyziologie účinky léků MeSH
- léková rezistence fyziologie účinky léků MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
