Coexistence of Parry-Romberg syndrome with homolateral segmental vitiligo

Parry-Romberg syndrome or progressive facial hemiatrophy was first described by Caleb Parry in 1825 and Moritz Romberg in 1846. This disorder is characterized by slowly progressing acquired unilateral hemifacial atrophy, which affects subcutaneous tissue together with the muscles and underlying bones. The pathogenesis and precise incidence of the syndrome remain unclear. Immune-mediated processes and disturbed central regulation, leading to the hyperactivity of the sympathetic nervous system, are primarily considered in the pathogenesis of this disorder. Parry-Romberg syndrome and localized scleroderma are considered to be interrelated as both of them have a similar clinicopathological appearance. We report the case of a 46-year-old man affected by both progressive atrophy of the left side of the face and homolateral, segmental vitiligo in the left side of the trunk and face

Design, Synthesis, Antibacterial Evaluations and In Silico Studies of Novel Thiosemicarbazides and 1,3,4-Thiadiazoles

The emergence of drug-resistant bacterial strains continues to be one of the major challenges of medicine. For this reason, the importance of searching for novel structures of antibacterial drugs chemically different from the currently known antibiotics is still of great importance. In this study, we synthesized the thiosemicarbazide and 1,3,4-thiadiazole derivatives and tested them for antibacterial activity. In in vitro tests, we examined the activity of the synthesized substances against Gram-positive and Gram-negative bacteria strains. While all 1,3,4-thiadiazoles tested lacked significant activity, the antimicrobial response of the thiosemicarbazides was moderate and it was also dependent on the type and position of the substituent on the phenyl ring. The highest activity towards all Gram-positive bacteria strains was shown by all three linear compounds containing the trifluoromethylphenyl group in the structure. The MIC (minimum inhibitory concentration) values were in the range of 3.9–250 µg/mL. Additionally, we try to explain the mechanism of the antibacterial activity of the tested compounds using the molecular docking to DNA gyrase and topoisomerase IV, following previous reports on the molecular basis of the activity of thiosemicarbazides. Docking simulations allow the purposing dual mechanism of the antibacterial activity of the synthesized compounds through inhibition of topoisomerase IV DNA gyrase with the moderate prevalence of the topoisomerase pathway

An Assessment of Serum Selenium Concentration in Women with Endometrial Cancer

Background: Numerous studies have shown a relationship between low serum selenium levels and an increased risk of developing cancer. Methods: A total of 306 women participated in the study: 153 patients diagnosed with endometrial cancer and 153 healthy women who were matched, in terms of birth year (+/−3 years), to the patients from the study group. The quantitative measurement of selenium content in the collected blood samples was performed using a mass spectrometer with excitation in inductively coupled plasma. In order to determine the relationship between the risk factors and the incidence of endometrial cancer, analyses based on single- and multi-factor conditional logistic regression models were performed. Results: The mean concentration of selenium was lower in patients with endometrial cancer than in healthy controls (60.63 µg/L (0.77 µmol/L) vs. 78.74 µg/L (0.99 µmol/L), respectively). When compared in quartiles, a significant association of lower selenium concentration with the incidence of endometrial cancer was recorded. The highest OR was observed in the first and second quartiles (OR-22.0, p-value < 0.001; medium selenium level 46.95 µg/L (0.59 µmol/L), and OR-5.94; p-value < 0.001; medium selenium level 63.60 µg/L (0.80 µmol/L), respectively). Conclusion: A strong correlation between the level of selenium in the blood serum and the risk of endometrial cancer indicates that patients with low levels should be a candidate group requiring appropriate preventive examinations. Further research on a larger group of patients is required

An Assessment of <i>GPX1</i> (rs1050450), <i>DIO2</i> (rs225014) and <i>SEPP1</i> (rs7579) Gene Polymorphisms in Women with Endometrial Cancer

Background: Numerous studies indicate a relationship between the presence of GPX1 (rs1050450), DIO2 (rs225014) and SEPP1 (rs7579) gene polymorphisms and the development of chronic or neoplastic diseases. However, there are no reports on the influence of these polymorphisms on the development of endometrial cancer. Methods: 543 women participated in the study. The study group consisted of 269 patients with diagnosed endometrial cancer. The control group consisted of 274 healthy women. Blood samples were drawn from all the participants. The PCR-RFLP method was used to determine polymorphisms in the DIO2 (rs225014) and GPX1 (rs1050450) genes. The analysis of polymorphisms in the SEPP1 (rs7579) gene was performed by means of TaqMan probes. Results: There was a 1.99-fold higher risk of developing endometrial cancer in CC homozygotes, DIO2 (rs225014) polymorphism (95% Cl 1.14–3.53, p = 0.017), compared to TT homozygotes. There was no correlation between the occurrence of GPX1 (rs1050450) and SEPP1 (rs7579) polymorphisms and endometrial cancer. Conclusion: Carriers of the DIO2 (rs225014) polymorphism may be predisposed to the development of endometrial cancer. Further research confirming this relationship is recommended

A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects

Background: Phosphodiesterase 10A (PDE10A) is expressed almost exclusively in the striatum and its inhibition is suggested to offer potential treatment in disorders associated with basal ganglia. We evaluated the selectivity, cytotoxicity, genotoxicity, pharmacokinetics and potential adverse effects of a novel PDE10A inhibitor, CPL500036, in vivo. Methods: The potency of CPL500036 was demonstrated by microfluidic technology, and selectivity was investigated in a radioligand binding assay against 44 targets. Cardiotoxicity in vitro was evaluated in human ether-a-go-go related gene (hERG)-potassium channel-overexpressing cells by the patch-clamp method and by assessing key parameters in 3D cardiac spheroids. Cytotoxicity was determined in H1299, HepG2 and SH-SY5Y cell lines. The Ames test was used for genotoxicity analyses. During in vivo studies, CPL500036 was administered by oral gavage. CPL500036 exposure were determined by liquid chromatography–tandem mass spectrometry and plasma protein binding was assessed. The bar test was employed to assess catalepsy. Prolactin and glucose levels in rat blood were measured by ELISAs and glucometers, respectively. Cardiovascular safety in vivo was investigated in dogs using a telemetry method. Results: CPL500036 inhibited PDE10A at an IC(50) of 1 nM, and interacted only with the muscarinic M2 receptor as a negative allosteric modulator with an IC(50) of 9.2 µM. Despite inhibiting hERG tail current at an IC(25) of 3.2 μM, cardiovascular adverse effects were not observed in human cardiac 3D spheroids or in vivo. Cytotoxicity in vitro was observed only at > 60 μM and genotoxicity was not recorded during the Ames test. CPL500036 presented good bioavailability and penetration into the brain. CPL500036 elicited catalepsy at 0.6 mg/kg, but hyperprolactinemia or hyperglycemic effects were not observed in doses up to 3 mg/kg. Conclusion: CPL500036 is a potent, selective and orally bioavailable PDE10A inhibitor with a good safety profile distinct from marketed antipsychotics. CPL500036 may be a compelling drug candidate