Opis przypadku mi´saka prà˝kowanokomórkowego pleomorficznego trzonu macicy

Abstract Pleomorphic rhabdomyosarcoma of the uterus is a rare malignant tumor. It is connected with postmenopausal abnormal vaginal bleeding and abdominal pain. We report a case of a 66-year-old postmenopausal woman diagnosed with abnormal vaginal bleeding and abdominal pain. Vaginal ultrasonography showed enlarged uterus, 82mm x 64mm in size. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with postoperative chemotherapy due to pleomorphic rhabdomyosarcoma of the uterus. The patient died 2,5 years after the surgery as a result of a rapid spread of the neoplastic process. The case of rhabdomyosarcoma, together with the review of the literature, is presented in the following work. We find that the rarity of this histological entity makes it particularly worthy of publication.Mięsak pleomorficzny, prążkowanokomórkowy jest rzadkim nienabłonkowym nowotworem złośliwym mięśnia macicy, występującym u pomenopauzalnych pacjentek, które zgłaszają w wywiadzie nieprawidłowe krwawienia maciczne i dolegliwości bólowe podbrzusza. W opisywanej sytuacji klinicznej 66 letnia wieloródka była hospitalizowana z powodu nieprawidłowego krwawienia z dróg rodnych oraz bólu podbrzusza. W badaniu USG uwidoczniono powiększony trzon macicy o wymiarach 82x64 mm. Przeprowadzono zabieg usunięcia macicy z przydatkami w sposób typowy. W badaniu histopatologicznym, potwierdzonym immunohistochemiczne, stwierdzono postać pleomorficzną mięsaka trzonu macicy. Po operacji pacjentka przeszła chemioterapię. Z powodu przerzutów pacjentka zmarła po około 2,5 roku od leczenia chirurgicznego. Z powodu bardzo rzadkiego występowania postaci pleomorficznej mięsaka prążkowanokomórkowego macicy, ten opis przypadku, łącznie z przeglądem literatury, wart jest opublikowania

Effect of Mycophenolate Mofetil on Plasma Bioelements in Renal Transplant Recipients

The proper concentrations of plasma bioelements may favorably reduce the incidence of metabolic disorders, which often occur during immunosuppressive therapy. Mycophenolate mofetil (MMF) is currently one of the most frequently administered immunosuppressive agents; however, MMF treatment is often related to gastrointestinal side effects. The aim of this study was thus to verify whether the MMF treatment itself, or its metabolite pharmacokinetics, has an effect on the concentrations of plasma bioelements. To determine this, the effect of MMF on the levels of both major (sodium [Na], potassium [K], calcium [Ca], magnesium [Mg]), and trace (iron [Fe], zinc [Zn], copper [Cu]) plasma bioelements in 61 renal transplant recipients was assessed in comparison to a control group (n = 45). The pharmacokinetic parameters of mycophenolic acid were determined by the high-performance liquid chromatography method. All patients filled out a 24-h diet history questionnaire. The results showed high plasma concentrations of Fe and low plasma concentrations of Mg and Zn as compared with diagnostic norms. The patients treated with MMF had significantly lower plasma Na (P < 0.001) and significantly higher plasma Zn (P = 0.030) and Cu concentrations (P < 0.001). In conclusion, MMF treatment was found to affect plasma Fe, Zn, and Cu levels by increasing their concentrations while decreasing the plasma Na concentration. Mg and Zn deficiencies, as well as excessive Fe levels, are frequently observed irrespective of the immunosuppressive regimen applied, which suggests that monitoring of these bioelements may be favorable

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

Effect of SUV39H1 Histone Methyltransferase Knockout on Expression of Differentiation-Associated Genes in HaCaT Keratinocytes

Keratinocytes undergo a complex differentiation process, coupled with extensive changes in gene expression through which they acquire distinctive features indispensable for cells that form the external body barrier&mdash;epidermis. Disturbed epidermal differentiation gives rise to multiple skin diseases. The involvement of epigenetic factors, such as DNA methylation or histone modifications, in the regulation of epidermal gene expression and differentiation has not been fully recognized yet. In this work we performed a CRISPR/Cas9-mediated knockout of SUV39H1, a gene-encoding H3K9 histone methyltransferase, in HaCaT cells that originate from spontaneously immortalized human keratinocytes and examined changes in the expression of selected differentiation-specific genes located in the epidermal differentiation complex (EDC) and other genomic locations by RT-qPCR. The studied genes revealed a diverse differentiation state-dependent or -independent response to a lower level of H3K9 methylation. We also show, by means of chromatin immunoprecipitation, that the expression of genes in the LCE1 subcluster of EDC was regulated by the extent of trimethylation of lysine 9 in histone H3 bound to their promoters. Changes in gene expression were accompanied by changes in HaCaT cell morphology and adhesion