Rational Design,Synthesis, and Potency of N‐Substituted Indoles,Pyrroles, and Triarylpyrazoles as Potential Fructose 1,6‐Bisphosphatase Inhibitors

By using computer modeling and lead structures from our earlier SAR results, a broad variety of pyrrole‐, indole‐, and pyrazole‐based compounds were evaluated as potential fructose 1,6‐bisphosphatase (FBPase) inhibitors. The docking studies yielded promising structures, and several were selected for synthesis and FBPase inhibition assays: 1‐[4‐(trifluoromethyl)benzoyl]‐1H‐indole‐5‐carboxamide, 1‐(α‐naphthalen‐1‐ylsulfonyl)‐7‐nitro‐1H‐indole, 5‐(4‐carboxyphenyl)‐3‐phenyl‐1‐[3‐(trifluoromethyl)phenyl]‐1H‐pyrazole, 1‐(4‐carboxyphenylsulfonyl)‐1H‐pyrrole, and 1‐(4‐carbomethoxyphenylsulfonyl)‐1H‐pyrrole were synthesized and tested for inhibition of FBPase. The IC₅₀ values were determined to be 0.991 and 1.34 μM , and 575, 135, and 32 nM , respectively. The tested compounds were significantly more potent than the natural inhibitor AMP (4.0 μM ) by an order of magnitude; indeed, the best inhibitor showed an IC₅₀ value toward FBPase more than two orders of magnitude better than that of AMP. This level of activity is virtually the same as that of the best currently known FBPase inhibitors. This work shows that such indole derivatives are promising candidates for drug development in the treatment of type II diabetes.     

Patient dose measurements in diagnostic radiology procedures in Montenegro

It was the aim of the study presented here to estimate for the first time patient dose levels in conventional diagnostic radiology in Montenegro. Measurements of patient dose in terms of entrance surface air kerma (ESAK) and kerma-area product (KAP) were performed on at least 10 patients for each examination type, in each of five randomly selected health institutions in Montenegro, so that a total of 872 patients for 16 different examination categories were included in the survey (817 patients for 1049 radiographies and 55 fluoroscopy patients). Exposure settings and individual data were recorded for each patient. Mean, median and third quartile values ESAK of patient doses are reported. The estimated mean ESAK values obtained are as follows: 4.7 mGy for pelvis anteroposterior (AP), 4.5 mGy for lumbar spine AP, 7.8 mGy for lumbar spine lateral (LAT), 3.1 mGy for thoracic spine AP and 4.3 mGy for thoracic spine LAT. When compared with the European diagnostic reference values, the mean ESAK for all studied examination types are found to be below the reference levels, except in chest radiography. Mean ESAK values for chest radiography are 0.9 mGy for posteroanterior (PA) projection and 2.0 mGy for LAT. The results exhibit a wide range of variation. For fluoroscopy examinations, the total KAP was measured. The mean KAP value per procedure for barium meal is found to be 22 Gy cm(2), 41 Gy cm(2) for barium enema and 19 Gy cm(2) for intravenous urography. Broad dose ranges for the same types of examinations indicate the necessity of applying practice optimisation in diagnostic radiology and establishment of national diagnostic reference levels.     

Mitigation of Sn Whisker Growth by Composite Ni/Sn Plating

Tin (Sn) is a key industrial material in coatings on various components in the electronics industry. However, Sn is prone to the development of filament-like whiskers, which is the leading cause of many types of damage to electronics reported in the last several decades. Due to its properties, a tin-lead (Sn-Pb) alloy coating can mitigate Sn whisker growth. However, the demand for Pb-free surface finishes has rekindled interest in the Sn whisker phenomenon. In order to achieve properties similar to those naturally developed in a Sn-Pb alloy coating, we carried out a study on deposited films with other Sn alloys, such as tin-bismuth (Sn-Bi), tin-zinc (Sn-Zn), and tin-copper (Sn-Cu), electrodeposited onto a brass substrate by utilizing a pulse plating technique. The results indicated that the Sn alloy films modified the columnar grain structure of pure Sn into an equiaxed grain structure and increased the incubation period of Sn whisker growth. The primary conclusions were based on analysis of the topography and microstructural characteristics in each case, as well as the stress distribution in the plated films computed by x-ray diffraction, and the␣amount of Sn whisker growth in each case, over 6 months under various environmental influences.     

The Effect of Micro-Alloying of Sn Plating on Mitigation of Sn Whisker Growth

Tin (Sn) is a key industrial material in coatings on various components in the electronics industry. However, Sn is prone to the development of filament-like whiskers, which is the leading cause of many types of damage to electronics reported in the last several decades. Due to its properties, a tin-lead (Sn-Pb) alloy coating can mitigate Sn whisker growth. However, the demand for Pb-free surface finishes has rekindled interest in the Sn whisker phenomenon. In order to achieve properties similar to those naturally developed in a Sn-Pb alloy coating, we carried out a study on deposited films with other Sn alloys, such as tin-bismuth (Sn-Bi), tin-zinc (Sn-Zn), and tin-copper (Sn-Cu), electrodeposited onto a brass substrate by utilizing a pulse plating technique. The results indicated that the Sn alloy films modified the columnar grain structure of pure Sn into an equiaxed grain structure and increased the incubation period of Sn whisker growth. The primary conclusions were based on analysis of the topography and microstructural characteristics in each case, as well as the stress distribution in the plated films computed by x-ray diffraction, and the?amount of Sn whisker growth in each case, over 6 months under various environmental influences.     

Effect of Hydrothermal Treatment of Rapeseed on Antioxidant Capacity of the Pressed Rapeseed Oil

Response surface methodology (RSM) was used to evaluate the quantitative effects of two independent variables, rapeseed moisture content and conditioning temperature, on the antioxidant capacity (AC) and total phenolic (TPC), tocopherol (TTC), and phosphorus contents (PC) in the pressed rapeseed oils. The mean AC results for the crude rapeseed oils ranged from 199.8 to 947.2 μmolTE/100 g. TPC and PC in the crude rapeseed oils correlated significantly (P < 0.01) and positively with AC of oils (R ² = 0.9498 and 0.4396, respectively). The experimental results of AC, TPC, and PC were close to the predicted values calculated from the polynomial response surface model equations (R ² = 0.9801, 0.9747 and 0.9165, respectively). The effect of oil processing temperature on AC and TPC was about 1.5 times greater than the effect of moisture level in rapeseed.     

PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (¹H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1β, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.     

The Use of Total Thrombus Formation Analysis System as a Tool to Assess Platelet Function in Bleeding and Thrombosis Risk—A Systematic Review

Background. Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot formation under blood flow conditions. For several years, researchers have been using a tool to analyse various clinical situations of patients to identify the properties and biochemical processes occurring within platelets and their microenvironment. Methods. An investigation of recent published literature was conducted based on PRISMA. This review includes 52 science papers directly related to the use of the Total Clot Formation Analysis System in relation to bleeding, surgery, platelet function assessment, anticoagulation monitoring, von Willebrand factor and others. Conclusion. Most available studies indicate that The Total Thrombus Formation Analysis System may be useful in diagnostic issues, with devices used to monitor therapy or as a significant tool for predicting bleeding events. However, T-TAS not that has the potential for diagnostic indications, but allows the direct observation of the flow and the interactions between blood cells, including the intensity and dynamics of clot formation. The device is expected to be of significant value for basic research to observe the interactions and changes within platelets and their microenvironment.     

Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis.