GABA receptor activity modulating piperine analogs: In vitro metabolic stability, metabolite identification, CYP450 reaction phenotyping, and protein binding.

In a screening of natural products for allosteric modulators of GABA receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABA and TRPV1 activating properties. We here investigated the metabolism of piperine and selected analogs in view of further cycles of lead optimization.

[RETROSPECTIVE ANALYSIS OF CAUSES ON UNSUCCESSFUL SURGICAL TREATMENT OF THE CHRONIC PANCREATITIS AND PANCREATIC CYSTS COMPLICATIONS].

Retrospective analysis of 108 observation files of 66 patients, operated on for chronic pancreatitis complications and 42 — for postnecrotic pancreatic cysts, using draining, resection—draining and resection operations, was conducted. Morphological changes in pancreatic parenchyma and pancreatic postnecrotic cysts at the operation time were compared with intraoperative blood loss, rate and character of intraoperative and post/ operative complications, depending on the kind, duration, volume and adequacy of the operations performed, as well as with lethality rate. Disadvantages in surgical treatment were noted in 57 (57%) patients, and 4 (3.

PRMT4-mediated arginine methylation negatively regulates retinoblastoma tumor suppressor protein and promotes E2F-1 dissociation.

The retinoblastoma protein (pRb/p105) tumor suppressor plays a pivotal role in cell cycle regulation by blockage of the G1-to-S-phase transition. pRb tumor suppressor activity is governed by a variety of posttranslational modifications, most notably phosphorylation by cyclin-dependent kinase (Cdk) complexes. Here we report a novel regulation of pRb through protein arginine methyltransferase 4 (PRMT4)-mediated arginine methylation, which parallels phosphorylation.

[Determination of the pancreatic inflammatory process activity in chronic pancreatitis].

There were 21 patients examined, who suffered chronic pancreatitis (CHP) in different activity of pancreatic inflammatory process. In the blood serum the contents of the inflammation markers was determined: tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), ratio TNF-alpha/IL-10 was calculated, as well as activity of elastase in feces. Analysis of these indices permits to estimate the activity of pancreatic inflammatory process in patients, suffering CHP, what secures rising of the preoperative diagnosis and treatment efficacy, as well as reduction of intra- and postoperative complications rate.