Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase

Platelets play a key role in hemostasis through their ability to rapidly adhere to activated or injured endothelium, subendothelial matrix proteins, and other activated platelets. A strong equilibrium between activating and inhibiting processes is essential for normal platelet and vascular function, impairment of this equilibrium being associated with either thrombophilic or bleeding disorders. Both cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) have been established as crucial and synergistic intracellular messengers that mediate the effects of platelet inhibitors such as nitric oxide (NO) and prostacyclin (PG-I2). However, it was recently suggested that a rapid cGMP/cGMP-dependent protein kinase (cGK)-mediated extracellular signal-related kinase (ERK) phosphorylation promotes platelet activation. This hypothesis was examined here by evaluating established and proposed cGK activators/inhibitors with respect to their capacity to promote either platelet activation or inhibition. In particular, the regulatory role of cGK for ERK phosphorylation and thrombin-, thromboxane-, and VWF-induced platelet activation was investigated. The data obtained do not support the concept that cGK-mediated ERK phosphorylation promotes platelet activation but confirm the inhibitory role of cGK in platelet function. One explanation for these discrepancies is the novel finding that extracellular cGMP analogs potently and rapidly inhibit thrombin-, thromboxane-, and VWF-induced human platelet signaling and activation by a cGK-independent mechanism.     

Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion

BACKGROUND The Pringle maneuver [portal triad obstruction(PTO)] provides huge disturbances during ischemia and even more thereafter in reperfusion.Contrarily, a possible solution may be stable gastric pentadecapeptide BPC 157,with already documented beneficial effects in ischemia/reperfusion conditions.Recently, BPC 157, as a cytoprotective agent, successfully resolved vessel occlusions in rats(ischemic colitis; deep vein thrombosis, superior anterior pancreaticoduodenal vein; bile duct cirrhosis) through rapid collateral vessel recruitment to circumvent vessel occlusion. Thereby, medication BPC 157 regimens were administered as a single challenge before and during ischemia or,alternatively, at various time points during reperfusion.AIM To introduce BPC 157 therapy against pringle maneuver-damage.METHODS In deeply anesthetised rats, the portal triad was clamped up for 30 min. Rats then underwent reperfusion for either 15 min or 24 h. Medication [(10 μg, 10 ng/kg)regimens, administered as a single challenge] picked(a) ischemia, PTO period [at 5 min before(ip) or at 5 or 30 min of ligation time(as a bath to PTO)] or(b)reperfusion, post-PTO period [at 1 or 15 min(bath during surgery) or 24 h(ip)reperfusion-time]. We provided gross, microscopy, malondialdehyde, serum enzymes, electrocardiogram, portal, caval, and aortal pressure, thrombosis and venography assessments.RESULTS BPC 157 counteracts electrocardiogram disturbances(increased P wave amplitude, S1Q3T3QRS pattern and tachycardia). Rapidly presented vascular pathway(portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein) as the adequate shunting immediately affected disturbed haemodynamics. Portal hypertension and severe aortal hypotension during PTO, as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated(during PTO) or completely abrogated(reperfusion); thrombosis in portal vein tributaries and inferior caval vein or hepatic artery was counteracted during portal triad obstruction PTO. Also, counteraction included the whole vicious injurious circle [i.e., lung pathology(severe capillary congestion), liver(dilated central veins and terminal portal venules), intestine(substantial capillary congestion, submucosal oedema, loss of villous architecture), splenomegaly, right heart(picked P wave values)] regularly perpetuated in ischemia and progressed by reperfusion in Pringle rats.CONCLUSION BPC 157 resolves pringle maneuver-damage in rats, both for ischemia and reperfusion.     

Efficacy of Reciprocating Instruments in Retreatment of Bioactive and Resin-Based Root Canal Sealers

ObjectiveTo compare the effectiveness of reciprocating instruments in removing gutta-percha and bioactive-based (BioRoot RCS and MTA Fillapex) and epoxy resin-based (AH Plus) sealers from root canals based on filling residues and the time required for root canal revision.Material and methodsRoot canals of 90 teeth were instrumented with Reciproc R40. All root canals were obturated using the single-cone technique with Reciproc R40 gutta-percha and with one of the selected sealers. Samples with oval, straight canals were used and randomly divided into three groups: (i) filled with AH Plus sealer and gutta-percha (n=30); (ii) filled with MTA Fillapex and gutta-percha (n=30); (iii) filled with BioRoot RCS and gutta-percha (n=30). Each group was divided into two subgroups (n=15) according to the retreatment instrument used (Reciproc M-Wire R25/R40 or Reciproc blue RB25/RB40). Root canals were longitudinally split and analyzed with a stereomicroscope at 15 × magnifications in the coronal, middle, and apical third. Computational analyses were performed with the Image J software. Data were compared using the Kruskal-Wallis test and Mann-Whitney U test.ResultsWhile no statistically significant differences in the residual material surface were found for Reciproc Blue, Reciproc M-Wire showed significantly higher residual material surface for AH Plus and MTA Fillapex compared to BioRoot RCS. For AH plus. Residual material surface was significantly lower for Reciproc Blue than for Reciproc M-Wire. In contrast, BioRoot RCS showed a significantly higher residual material surface for Reciproc Blue.ConclusionsCalcium silicate-containing sealers were more retrievable compared to AH Plus, with fewer sealer remnants and shorter retreatment time. Retreatment with Reciproc M-Wire instruments was superior to Reciproc blue instruments in retreatment of BioRoot RCS. However, none of the sealers were removed completely.     

Parents’ Pain Catastrophizing is Related to Pain Catastrophizing of Their Adult Children

Background  

Parents’ pain behavior is associated with the way their children experience and express pain.     

Evaluation of the Food Choice Motives before and during the COVID-19 Pandemic: A Cross-Sectional Study of 1232 Adults from Croatia

The coronavirus disease 2019 pandemic brought changes to almost every segment of our lives, including dietary habits. We present one among several studies, and the first on the Croatian population, aiming at investigating changes of food choice motives before and during the pandemic. The study was performed in June 2021 as an online-based survey, using a 36-item Food Choice Questionnaire applied for both the periods before and during the pandemic. The final sample consisted of 1232 adults living in Croatia. Sensory appeal was ranked as the number one most important food choice motive before, whereas health was ranked as the number one most important food choice motive during the pandemic. Ethical concern was reported as the least important food choice motive both before and during the pandemic. In women, natural content (p = 0.002), health, convenience, price, weight control, familiarity, and ethical concern (all p < 0.001) became more important during the pandemic, while price (p = 0.009), weight control, familiarity, and ethical concern (all p < 0.001) became more relevant for men. All together, these can be considered favorable changes toward optimal diets and may result in beneficial influences on health and lifestyle. Education strategies and efficiently tackling misinformation are prerequisites for informed food choice, which will ensure long-lasting positive effects of such changes.     

Successful Implementation of Integrated Care in Slovenian Primary Care

For the purpose of celebrating the 40th anniversary of Alma Ata declaration, the WHO published a successful model of integrated patient care being performed in Slovenia. After two years, the WHO experts evaluated the success in practise during a visit to the Slovenian primary care environment. This report showed that Slovenia was a notable exception regarding developing effective primary care systems. The country has an impressive primary care which performs very well.