Docetaxel je cytostatikum užívané v adjuvantní, neoadjuvatní i paliativní léčbě karcinomu prsu. Je podáván jako monoterapie či jako součást kombinovaných režimů. Taxany obecně spolu s antracykliny patří mezi nejefektivnější chemoterapeutika využívané v léčbě karcinomu prsu. Zařazení docetaxelu do léčebného schématu karcinomu prsu přineslo zlepšení celkového přežití a prodloužení období bez nemoci u pacientek léčených adjuvantně a větší procento léčebných odpovědí, prodloužení doby do progrese a celkového přežití při léčbě paliativní (1, 2, 3, 4, 5). Při využívání docetaxelu v léčbě je potřeba mít na paměti, že se jedná o chemoterapeutikum s nezanedbatelnými nežádoucími účinky. Cílem naší retrospektivní studie bylo vyhodnocení akutní toxicity při léčbě režimy s docetaxelem a zvážení možností léčby akutní toxicity., Docetaxel is a cytostatic drug used in adjuvant, neoadjuvant as well as palliative treatment of breast cancer. It is administered as monotherapy or as part of combination regimens. Taxanes along with anthracyclines are among the most efficacious chemotherapeutic drugs used in the treatment of breast cancer. Inclusion of docetaxel in the therapeutic regimen for breast cancer has resulted in improved overall survival and extended disease-free interval in patients treated with adjuvant therapy and in a greater proportion of therapeutic responses as well as extended time-to-progression and overall survival with palliative therapy (1, 2, 3, 4, 5). It must be kept in mind that, when used for treatment, docetaxel is a chemotherapeutic drug with non-negligible adverse effects. The aim of our retrospective study was to evaluate acute toxicity of therapeutic regimens with docetaxel and to consider the options for the treatment of acute toxicity., Kateřina Krošláková, Milan Kohoutek, Markéta Pospíšková, and Literatura
Toxická epidermální nekrolýza je vzácné, akutní, život ohrožující onemocnění projevující se rozsáhlým odlučováním epidermis a slizničních povrchů. Jde o závažnou nežádoucí reakci na podávané léky, nejčastěji antibiotika, antikonvulziva či nesteroidní antirevmatika. Jako první ji popsal skotský dermatolog Alan Lyell v roce 1956, proto je též nazývána Lyellův syndrom. Mortalita tohoto onemocnění je vysoká, proto je klíčová včasná diagnostika a neodkladné zahájení adekvátní péče o pacienta. Jedná se o vzácné onemocnění s velmi malou incidencí a závažnou prognózou, což značně ztěžuje provedení velkých randomizovaných klinických studií. Je tedy obtížné hodnotit efektivitu jednotlivých terapeutických možností. Jako nejperspektivnější se prozatím jeví nitrožilní podávání imunoglobulinů se zřejmým zlepšením klinického stavu pacienta, dobrou tolerancí a minimálními vedlejšími nežádoucími účinky. Nové experimentální postupy se snaží hledat cestu terapie cíleným ovlivněním granulyzinu jakožto hlavního cytotoxického mediátoru. Klíčová slova: anamnéza – apoptóza keratinocytů – cyklosporin A – granulyzin – hodnocení SCORTEN – intravenózní imunoglobuliny – interdisciplinární péče – kortikosteroidy – Nikolského fenomén – plazmaferéza – poléková reakce – Stevensův-Johnsonův syndrom – toxická epidermální nekrolýza, Toxic epidermal necrolysis is a rare, acute and life-threatening disorder manifested by extensive separation of the epidermis and mucosal surfaces. It is a serious adverse response to administered drugs, mostly antibiotics, anticonvulsants or NSAIDs. First described by Scottish dermatologist Alan Lyell in 1956, it is also known as Lyell’s syndrome. Mortality of the disease is high, therefore its early diagnosis is crucial and immediate initiation of appropriate patient care necessary. It is a rare disease with a very low incidence and serious prognosis, which is a considerable hindrance to undertaking large randomized clinical studies. It is therefore difficult to evaluate the effectiveness of various therapeutic options. As the most promising so far appears the administration of intravenous immunoglobulins, apparently reaching improvement in the clinical condition of the patient, with a good tolerances and minimal side adverse effects. New experimental techniques endeavour to seek a way to the therapy through targeted influencing of granulysin as the major cytotoxic mediator. Key words: adverse drug reaction – corticosteroids – cyclosporine A – granulysin – intravenous immunoglobulins – interdisciplinary team care – keratinocyte apoptosis – medical history – Nikolsky´s sign – plasmapheresis – SCORTEN score – Stevens-Johnson syndrome – toxic epidermal necrolysis, and Dina Odarčenková, Milan Kvapil
The aim of the present work was to determine whether Dermacentor reticulatus (Fabricius), tick species common in eastern Poland could be infected with Toxoplasma gondii (Nicolle et Manceaux, 1908). A total of 664 unfed D. reticulatus ticks were collected from six localities of Lublin province (eastern Poland) within the framework of study for the presence of bacterial, viral and parasitological infections, with use of PCR and confirmed by sequencing analysis. The prevalence of T. gondii DNA of B1 gene in the total examined D. reticulatus ticks was 3.2%. The infection varies greatly depending on the locality of tick collection (0-16.7%). Preliminary identification of clonal type (I or II/III) by Restriction Fragments Length Polymorphism PCR (RFLP-PCR) with use B1 gene showed that all isolates of T. gondii belonged to type I. RFLP analysis using genetic markers SAG1, 5'-SAG2, 3'-SAG2, SAG3, and GRA6 on B1-positive samples showed that only a single isolate proved to be type I with all five markers, another type was classified to type I according to four markers, while another five isolates had only type I alleles at GRA6, which cannot be regarded as type I confirmation. It must be pointed out that the used DNA isolation method by boiling with ammonium hydroxide enables to receive the total DNA from ticks, but may be not quite suitable for genotyping. In conclusion, this study indicates that besides Ixodes ricinus (Linnaeus), also D. reticulatus should be considered as a potential vector of T. gondii. The presumption of tick-borne transmission as an alternative pathway of disease spreading could well explain the high prevalence of toxoplasmosis among the herbivorous mammals and birds. However, this hypothesis needs verification by further experimental and ecological studies., Angelina Wójcik-Fatla, Jacek Sroka, Violetta Zając, Anna Sawczyn, Ewa Cisak, Jacek Dutkiewicz., and Obsahuje bibliografii
Screening and identification of protective antigens are essential for the prevention of infections with Toxoplasma gondii (Nicolle et Manceaux, 1908). In our previous study, T. gondii ribosomal-ubiquitin protein L40 (TgRPL40) was identified as a circulating antigen. However, the function and protective value of TgRPL40 was unknown. In the current study, recombinant TgRPL40 was expressed in Escherichia coli BL21 and antibody was prepared. Western blotting analysis indicated that TgRPL40 was present in circulating antigens and excretory/secretary antigens (ESA). Immunofluorescence and immunoelectron microscopy analysis revealed that TgRPL40 protein is widely distributed in the tachyzoites. Immunisation with recombinant TgRPL40 prolonged the survival of mice infected with tachyzoites. Quantitative real-time polymerase chain reaction analysis showed that immunisation with recombinant TgRPL40 reduced the parasite burden in blood, liver, spleen and brain of mice infected with tachyzoites. These observations indicate that TgRPL40 is a circulating antigen and is an effector of immune protection against acute T. gondii infection.
The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects humans resulting in acute toxoplasmosis, an infection that in immunocompetent people is typically mild but results in persistent latent toxoplasmosis. In that T. gondii appears to affect dopamine synthesis and because addicting drugs affect midbrain dopamine transmission, latent toxoplasmosis could influence substance use. Using both the third and continuous National Health and Nutrition Examination Surveys from the US Centers for Disease Control and Prevention, we used logistic regression to test for associations between T. gondii seropositivity and subject self-report of having ever used tobacco, alcohol, marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset, which included data for tobacco, alcohol, marijuana and cocaine, T. gondii seropositivity was associated with a reduced likelihood of self-reported marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72 [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition Examination Surveys dataset, which included data for all six substances, T. gondii seropositivity was associated with a reduced likelihood of self-reported tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95% CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005) and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed interactions between sex and T. gondii seropositivity in the prediction of self-reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared to remove the protective effect of education and economic status against self-reported cigarette smoking. These findings suggest that T. gondii seropositivity may be inversely associated with some but not all types of substance use in US adults., Andrew N. Berrett, Shawn D. Gale, Lance D. Erickson, Evan L. Thacker, Bruce L. Brown, Dawson W. Hedges., and Obsahuje bibliografii