Contemporary use of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction referred to primary percutaneous coronary interventions in Poland: Data from ORPKI national registry

Journal of Thrombosis and Thrombolysis - According to guidelines, it is recommended to give P2Y12 inhibitors (preferably ticagrelor or prasugrel) at the time of first medical contact in patients...     

Highly selective inhibition of butyrylcholinesterase by a novel melatonin–tacrine heterodimers

Novel inhibitors of cholinesterases, especially butyrylcholinesterase (BuChE), were obtained by coupling melatonin–tacrine heterodimers via the carbamate bond. Compounds 14a‐i possessed potent cholinesterase inhibitory activity (with IC₅₀ values as low as 1.18 nm for acetylcholinesterase (AChE) and 0.24 nm for butyrylcholinesterase (BuChE)). These heterodimers exhibit selectivity toward BuChE, being from 4‐ to 256‐fold more active toward BuChE than AChE, but still acting as better AChE inhibitors than tacrine 4 .     

Colorectal carcinoma in Poland in 1975 and 1995: not only more,but also different

BACKGROUND AND AIMS: We previously reported that the sole clinicopathological parameters of carcinomas diagnosed in a single institution in 1975 differed from those in patients diagnosed in 1995. The findings might be compatible with the loss of importance of the microsatellite instability of the carcinogenic pathway. MATERIALS AND METHODS: We examined the microsatellite status and selected immunomarkers (Ki-67, p53, BAX) in the archival material from 1975 (n=76) and 1995 (n=105). RESULTS AND CONCLUSION: The distribution of tumors showing no microsatellite instability, low microsatellite instability, and high microsatellite instability in the 2-yearly cohorts was similar (1975: 55.6%, 22.2%, 22.2%; 1995: 60.2%, 20.4%, 19.4%, respectively). The percentage of carcinomas showing microsatellite instability at the APC locus differed significantly (1975: 37.5%; 1995: 21.4%). The typical clinicopathological parameters of carcinomas exhibiting high microsatellite instability were largely shared by the carcinomas demonstrating instability at the APC locus. The carcinomas resected in 1995 more frequently demonstrated high expression of an antiapoptotic protein BAX and a different distribution of their Ki-67 proliferation fraction. The evolution of colorectal carcinoma in Poland also involves qualitative changes, including its genetic background.     

VPS35 and DNAJC13 disease-causing variants in essential tremor

Exome-sequencing analyses have identified vacuolar protein sorting 35 homolog (VPS35) and DnaJ (Hsp40) homolog, subfamily C, member 13 (DNAJC13) harboring disease-causing variants for Parkinson disease (PD). Owing to the suggested clinical, pathological and genetic overlap between PD and essential tremor (ET) we assessed the presence of two VPS35 and DNAJC13 disease-causing variants in ET patients. TaqMan probes were used to genotype VPS35 c.1858G>A (p.(D620N)) (rs188286943) and DNAJC13 c.2564A>G (p.(N855S)) (rs387907571) in 571 ET patients of European descent, and microsatellite markers were used to define the disease haplotype in variant carriers. Genotyping of DNAJC13 identified two ET patients harboring the c.2564A>G (p.(N855S)) variant previously identified in PD patients. Both patients appear to share the disease haplotype previously reported. ET patients with the VPS35 c.1858G>A (p.(D620N)) variants were not observed. Although a genetic link between PD and ET has been suggested, DNAJC13 c.2564A>G (p.(N855S)) represents the first disease-causing variant identified in both, and suggests the regulation of clathrin dynamics and endosomal trafficking in the pathophysiology of a subset of ET patients.     

The effects of perinatal hypoxia on the behavioral,neurochemical, and neurohistological toxicity of the metabolic inhibitor 3-nitropropionic acid

3-nitropropionic acid (3-NPA) neurotoxicity and long-term effects of perinatal hypoxia were evaluated in 18 adult rats. Hypoxia-insulted (I) and noninsulted (NI) rats were delivered by cesarean section. Hypoxic insult was effected by submerging dissected uterine horns in warmed saline for 15 min. NI rats were delivered from the adjacent nonsubmerged horns. At postnatal day 90, I and NI rats were trained to perform tasks thought to measure behaviors dependent upon aspects of time estimation (TE), motivation, and learning. At 12 months of age, rats were injected i.p. with escalating doses of 3-NPA (5 mg/kg/day to a maximum of 30 mg/kg/day) immediately after each test session and sacrificed at the end of treatment. Additional male rats were used as untreated controls. Although 3-NPA produced a dose-dependent impairment of performance in each task, the effects were qualitatively similar for each group. A significant difference between I and NI rats was, however, observed in the TE task where NI rats completed less of the task at high doses of 3-NPA compared to I rats. Compared to untreated controls, dopamine concentrations were decreased in caudate nucleus of both I and NI rats after 3-NPA. Specific areas most frequently damaged included cerebral cortex, hippocampal subfield CA1, thalamus, caudate nucleus, and the cerebellum. Lesions usually were less extensive in the I rather than NI members of a littermate pair, suggesting a possible protective effect of perinatal hypoxia against subsequent 3-NPA neurotoxicity.