Syndrom Birt-Hogg-Dubé (BHDS, MIM 135150) je autozomálně dominantně dědičné onemocnění charakterizované výskytem kožních fibrofolikulomů, plicních cyst, spontánního pneumothoraxu a nádorů ledviny. Příčinou onemocnění jsou zárodečné mutace genu FLCN, který kóduje protein folliculin. Onemocnění je vzácné, má vysokou penetranci, variabilní expresivitu. Doporučení zahrnují zvýšenou pozornost při výkonech v celkové anestezii pro riziko pneumothoraxu a dlouhodobé klinické sledování pro zvýšené riziko nádorů ledvin. Diagnostická a prediktivní DNA diagnostika BHDS je dostupná, prenatální, preimplantační diagnostika je možná.
Birt-Hogg-Dubé syndrome (BHDS, MIM 135150) is an autosomal dominant condition characterized by presence of skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal cancer. The disease is caused by germ-line mutations of the FLCN gene, which encodes protein folliculin. BHDS is a rare condition with high penetrance and variable expression. Clinical recommendations include increased care during general anesthesia due to a higher risk of pneumothorax, and long-term follow-up due to an elevated risk of renal cancer. Diagnostic and predictive DNA tests are available; prenatal and preimplantation diagnosis is possible.
- Keywords
- gen FLCN, folliculin, fibrofolikulom, pneumothorax, nádor ledviny,
- MeSH
- Birt-Hogg-Dube Syndrome diagnosis genetics therapy MeSH
- Cysts genetics therapy MeSH
- Diagnosis, Differential MeSH
- Financing, Organized MeSH
- Genetic Diseases, Inborn diagnosis prevention & control therapy MeSH
- Genetic Testing methods trends utilization MeSH
- Skin Diseases diagnosis genetics therapy MeSH
- Humans MeSH
- Tumor Suppressor Proteins genetics isolation & purification MeSH
- Kidney Neoplasms diagnosis therapy MeSH
- Lung Diseases diagnosis genetics MeSH
- Pneumothorax diagnosis therapy MeSH
- Preventive Medicine methods trends MeSH
- Proto-Oncogene Proteins genetics isolation & purification MeSH
- Age Factors MeSH
- Check Tag
- Humans MeSH
A new and diastereoselective method for the synthesis of the estrone skeleton from a substituted styrene based on sequential 3-fold use of Cp 2ZrBu 2 (oxidative addition-alkylation and two cyclization-alkylation sequences) and a ruthenium complex catalyzed RC-metathesis of a sterically hindered diene was developed. The prepared estratetraene was obtained in 7 steps from a commercially available starting material and thus the overall synthesis of estrone could be accomplished in 9 steps. Moreover, we have also found that the course of the reaction of substrates bearing the 2-halo-1,7-diene moiety with Cp 2ZrBu 2, i.e., cyclization or oxidative addition to the C-X bond, could be controlled by the nature of the halogen leaving group.
A development of robust and rapid method with simple sample preparation for the analysis of steroids of C18-, C19-, C21- families is of interest of many research groups. Here we present a novel LC-MS/MS method for the simultaneous quantification of 32 steroid hormones in human plasma. Twenty-two of them were analyzed directly without the need for derivatization, while ten were derivatized with 2-fluoro-1-methylpyridinium p-toluenesulfonate. The steroids were separated on a C18 column with a gradient elution consisting of methanol and water with the addition of 0.1% formic acid. The mass spectrometer was operated in positive ESI mode. Validation demonstrated that the method was applicable for the quantitative analysis of two C18- steroids (estrone, estradiol), nineteen C19- steroids (testosterone, epitestosterone, dihydrotestosterone, 11-ketodihydrotestosterone, 11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketotestosterone, dehydroepiandrosterone, 7α-hydroxydehydroepiandrosterone, 7β-hydroxydehydroepiandrosterone, 7-ketodehydroepiandrosterone, androsterone, epiandrosterone, androstenedione, androstenediol, 5α-androstane-3α,17β-diol, 5α-androstane-3β,17β-diol, 5β-androstane-3α,17β-diol, 5β-androstane-3β,17β-diol), and eleven C21- steroids (cortisol, 21-deoxycortisol, 11-deoxycortisol, cortisone, corticosterone, 11-deoxycorticosterone, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, 5α-dihydroprogesterone). The lower limits of quantification are appropriate for analyses in both physiological and various pathophysiological conditions. The accuracy, intra- and inter-day precision values as well as stability tests were in accordance with FDA Guidelines. The method will be a useful tool in investigating the mechanisms of steroid-related diseases and will serve as a steppingstone for the development of other methods for steroid analyses in various biological matrices such as prostate tissue, cerebrospinal fluid, urine, seminal fluid, and saliva.
- MeSH
- Androgens MeSH
- Androstenedione * MeSH
- Chromatography, Liquid methods MeSH
- Estrone MeSH
- Humans MeSH
- Tandem Mass Spectrometry * methods MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
Bisphenol A (BPA) is a widely known endocrine disruptor with estrogenic, antiestrogenic or antiandrogenic properties. BPA could interfere with estrogen metabolism as well with receptor-mediated estrogen actions. Both environmental BPA and estrogens may be traced in body fluids, of which, besides the blood plasma, the seminal fluid is of particular interest regarding their possible interactions in the testis. The method for simultaneously determining BPA and estrogens is then needed, taking into account that their concentrations in these body fluid may differ. Here the method was developed and validated for measurements of BPA, estrone (E1), estradiol (E2) and estriol (E3) in blood plasma and seminal plasma using liquid chromatography-tandem mass spectrometry. Due to the phenolic moiety of all compounds, dansyl chloride derivatization could be used. The analytical criteria of the method with respect to expected concentration of the analytes were satisfactory. The lower limits of quantifications (LLOQ) amounted to 43.5, 4.0, 12.7, 6.7 pg/mL for plasma BPA, E1, E2 and E3, and 28.9, 4.9, 4.5, 3.4 pg/mL for seminal BPA, E1, E2 and E3, respectively. The concentrations of individual steroids differed between body fluids. To the best of our knowledge, this is the first method that enabled the measurement of estrogens and BPA together in one run. The concentrations of E1, E2 and for the first time also of E3 in seminal plasma in normospermic men are reported.
- MeSH
- Benzhydryl Compounds analysis blood MeSH
- Chromatography, Liquid methods MeSH
- Endocrine Disruptors analysis blood MeSH
- Estrogens analysis blood MeSH
- Estrone analysis blood MeSH
- Phenols analysis blood MeSH
- Humans MeSH
- Limit of Detection MeSH
- Semen chemistry MeSH
- Tandem Mass Spectrometry methods MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Validation Study MeSH
There were synthesized new types of ribbon type steroidal dimers derived from three types of steroidal skeletons (cholic acid, etienic acid, estrone) using Cu(I) catalyzed 1, 3-dipolar cycloaddition reaction. Steroid parts of the molecular "ribbons" are linked by heterocyclic moiety, namely by 2,6-bis((1H-1,2,3-triazol-1-yl)-methyl)pyridine. Compounds synthesized possess different cytotoxic and hormone receptor modulating activities.
- MeSH
- Androstenes chemistry MeSH
- Hormone Antagonists chemical synthesis pharmacology MeSH
- Cytotoxins chemical synthesis pharmacology MeSH
- Estrone chemistry MeSH
- Catalysis MeSH
- Cholic Acid chemistry MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Pyridines chemistry MeSH
- Receptors, Steroid antagonists & inhibitors metabolism MeSH
- Steroids chemical synthesis pharmacology MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
