Comparison of Renal Hemodynamic Effect of Ramiprilat to Captopril: Possible Role of Kinins

Sincetheintroductionofthefirstlineofangiotensinconvertingenzyme(ACE)inhibitors,ofwhichcaptoprilistheprototype,morepotentlonger-lastingagentshavebecomeavailable[l].AmongtheseisramipriIat,anonsL1lfhydrylACEinhibitorsimilarchemicallytoenalaprilatbutcontaininginadditionapentanering.Benderetal[2Jdemonstratedinvitrothatramiprilatisatleast23timesmorelipophilicthanenalaprilatwithanaffinityforACE47timesgreatc'rthanthatofcaptopril.ItwaspostulatedthatthemorelipophiIicanACEinhibitor,thebetteraccessi…     

Disease Behavior in Children with Crohn’s Disease: The Effect of Disease Duration, Ethnicity, Genotype, and Phenotype

Background Disease behavior in Crohn’s disease (CD) may be modified by disease location and genotype. Disease behavior may change over time, and thus analysis requires follow-up. To date, there have been few pediatric studies that have evaluated the association between disease behavior and genotype with prolonged follow-up. The aim of our study was to evaluate the effect of genotype, phenotype, and ethnicity on disease behavior in pediatric CD. Methods Evaluation of 128 pediatric CD was followed by analysis of 232 pediatric and adult-onset CD patients. Inclusion required at least 2 years of follow-up. Phenotype, ethnicity, and disease duration were recorded. Patients were genotyped for polymorphisms in the NOD2/CARD15 gene. Results Colonic involvement was more frequent in younger patients. Pediatric disease at end of follow-up was classified as inflammatory (78%), penetrating (7%), and stricturing (17%). Duration of follow-up (mean 4.9 pediatric and 6.4 years mixed) was associated with more stricturing and penetrating disease. There was no association between mean age of onset and NOD2/CARD15, or either of these with disease behavior. These observations were replicated in the mixed cohort. Sephardic Jewish origin was inversely correlated with inflammatory behavior (P = 0.006), independent of NOD2/CARD15 genotype. Conclusions Duration of disease and ethnicity, irrespective of NOD2/CARD15 genotype and age of onset, were the only predictors for penetrating or stricturing disease. Ron Shaoul, Esther Leshinsky-Silver, and Arie Levine contributed equally in this endeavor.     

The Hepatocarcinogenic Effect of Methionine and Choline Deficient Diets: An Adaptation to the Warburg Effect?

Normal differentiated hepatocytes primarily metabolize methionine, via homocysteine synthesis, through the transsulfuration pathway. In addition to glutathione, this pathway produces α-ketobutyrate that is further metabolized in the mitochondria. It is only under low methionine conditions that differentiated hepatocytes predominantly regenerate methionine from homocysteine. In contrast, proliferating hepatocytes and liver cancer cells regenerate methionine from homocysteine regardless of the availability of methionine. Here we propose that this less efficient metabolism of methionine in proliferating hepatocytes and cancer cells is an adaptation to the "Warburg effect" that is, to the well known phenomenon that cancer cells rely on aerobic glycolysis instead of oxidative phosphorylation to generate energy. The observation that knockout mice with impaired S-adenosylmethionine (SAMe) synthesis (the first step in methionine metabolism) or catabolism spontaneously develop fatty liver and hepatocellular carcinoma, together with the observation that SAMe administration induces apoptosis in hepatoma cells and prevents liver cancer support this hypothesis.     

Effect of Aspirin Coadministration on the Safety of Celecoxib,Naproxen, or Ibuprofen

Background

The safety of nonsteroidal anti-inflammatory drug (NSAID) and aspirin coadministration is uncertain.

Effect of primaquine on the gametocyte, gametogony and sporogony of Plasmodium yoelii niger-ensis.

Mice carrying Plasmodium yoelii nigeriensis were given intragastrically with primaquine 1.25mg/kg and 1.95 mg/kg,respectively.8 h after treatment,the number of gametocytes in the blood wasreduced by 50％,some gametocytes appearing abnormal.The decrease in the number of ookinetes,the infective rate and infective degree of oocysts and gland infection rate was proportional to theincrease in primaquine dosage and the infection time of mosquitoes,In the m(?)antime,some ookinetes     

Effect of telehealth interventions on major cardiovascular outcomes: a meta-analysis of randomized controlled trials

Background Telehealth interventions (THI) were associated with lower levels of cardiovascular risk factors in adults, whereas the effect of THI on cardiovascular disease (CVD) still remains controversial. A meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCT) which investigated potential impact of THI on the incidence of CVD in patients with or without prior CVD. Methods PubMed, EmBase, and the Cochrane Library were searched to identify RCTs to fit our analysis through December 2016. Relative risk (RR) with its 95% confidence interval (CI) was used to measure the effect of THI using a random-effect model. Sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. Results Eight RCTs were included and with a total of 1635 individuals. The summarized results indicated that participants who received THI showed a significant reduction of the CVD incidence as compared with usual care (RR: 0.59; 95% CI: 0.47–0.74; P < 0.001). Furthermore, the effect of THI was greater in patients with history of CVD (RR: 0.55; 95% CI: 0.44–0.70; P < 0.001) than in patients without history of CVD (RR: 0.99; 95% CI: 0.51–1.94; P = 0.977). Sensitivity analysis suggested that the intervention effect persisted and the conclusion was not changed. Subgroup analysis indicated mean age, study quality might play an important role on the risk of CVD. Conclusions The findings of this study indicated THI could reduce the recurrence of CVD. Further large-scale trials are needed to verify the effect of THI on CVD in healthy individuals.     

Management of Recurrence of Symptoms of Gastroesophageal Reflux Disease: Synergistic Effect of Rebamipide with 15 mg Lansoprazole

Background  

Proton pump inhibitors (PPIs) are effective in healing reflux esophagitis and relieving the symptoms of gastroesophageal reflux disease (GERD). Prevention of recurrence of symptoms has become a therapeutic aim in patients with these conditions.     

Influence of three-dimensional nanoparticle branching on the Young’s modulus of nanocomposites: Effect of interface orientation

With the availability of nanoparticles with controlled size and shape, there has been renewed interest in the mechanical properties of polymer/nanoparticle blends. Despite the large number of theoretical studies, the effect of branching for nanofillers tens of nanometers in size on the elastic stiffness of these composite materials has received limited attention. Here, we examine the Young''s modulus of nanocomposites based on a common block copolymer (BCP) blended with linear nanorods and nanoscale tetrapod Quantum Dots (tQDs), in electrospun fibers and thin films. We use a phenomenological lattice spring model (LSM) as a guide in understanding the changes in the Young''s modulus of such composites as a function of filler shape. Reasonable agreement is achieved between the LSM and the experimental results for both nanoparticle shapes—with only a few key physical assumptions in both films and fibers—providing insight into the design of new nanocomposites and assisting in the development of a qualitative mechanistic understanding of their properties. The tQDs impart the greatest improvements, enhancing the Young''s modulus by a factor of 2.5 at 20 wt.%. This is 1.5 times higher than identical composites containing nanorods. An unexpected finding from the simulations is that both the orientation of the nanoscale filler and the orientation of X-type covalent bonds at the nanoparticle-ligand interface are important for optimizing the mechanical properties of the nanocomposites. The tQD provides an orientational optimization of the interfacial and filler bonds arising from its three-dimensional branched shape unseen before in nanocomposites with inorganic nanofillers.Polymer−nanoparticle composites have become a highly active topic of research with rapidly expanding applications (1), in part because of their high polymer−particle interfacial area and the unique shape- and size-dependent, tunable properties of nanoparticle reinforcements. For example, new polymer nanocomposites have been developed that can optically sense stress concentration (2), are responsive to magnetic, electrical, and thermal actuation (3, 4), and exhibit large changes in elastic modulus and glass transition temperature at low nanoparticle concentrations (5).While theoretical studies show that the Young’s modulus of such polymer nanocomposites depends on nanoparticle shape (6), experimental studies are limited. Experimental studies on polymers (7) include the synergistic reinforcement effects of multiple nanocarbons (8) and the shape-dependent reinforcement effects of micrometer-sized tetrapods (9), microscale ceramic needles (10), carbon nanotubes (11), clay-based nanocomposites (12, 13), and others (14). Computational studies include the effects of nanoparticle packing and size on the nanocomposite Young’s modulus (15–17). However, the effects of increasing nanoparticle branching on the mechanical behavior of nanocomposites have not been demonstrated (18). It is possible to make nanocrystals with controlled shapes and degree of branching (19); as such, they pose an ideal system to study the effect of reinforcement branching.Here, using nanorods (NRs) and tetrapod quantum dots (tQDs) in both electrospun fibers and solvent-cast films, we study the effect of increasing nanoparticle branching on the Young’s modulus of a common structural elastomer, poly(styrene block−ethylene−butylene block−styrene) (SEBS) (20). We chose SEBS since it is a widely used structural copolymer, has a 40% phase (ethylene−butylene) of similar chemical makeup as our nanoparticle surface ligands (although it is incompatible with 60% of the polymer, the polystyrene (PS) phase), and is amorphous, allowing for improved intercalation with the nanoparticles. In choosing polymer−filler nanocomposites, there is a critical choice to be made between the case where the polymer−filler interaction is very strong, in which case the intrinsic polymer structure is disrupted to a high degree, and the case where it is weak, leaving the native polymer structure largely unperturbed. Both limits are of significant interest, but in this first study, we focus on the latter weak interface case, as it is by far the most common case in practical composites and it is the case that is most amenable to modeling through summation of mechanically independent components. In such a case, the nanoparticles form nanoscopic aggregates distributed throughout the SEBS matrix, due to the van der Waals interactions between the native alkyl ligands on the nanoparticles and the SEBS polymer. No macrophase separation was observed, and no surface modification was performed to achieve single nanofiller dispersion. Future studies will be directed at the single-filler dispersed case, where the filler−polymer interaction is much stronger. In the stronger interface case, the nanoparticles may be selectively incorporated within one block copolymer (BCP) microdomain, and, due to their size, the intrinsic local polymer chain conformation may be more affected by the presence of the filler.In both electrospun fibers and films, we observed nanoscopic aggregates of nanofillers (∼150 nm in diameter), and we found that the multiple-branched tQDs improved the Young’s modulus the most compared with linear shapes, i.e., nanoscale branching may optimize the Young’s modulus. Our simulated results using a 2D lattice spring model (LSM) suggest that this shape effect on the Young’s modulus is primarily due to the orientation of the strong X-type bonds (21) at the nanoparticle−ligand interface. This illustrates the importance of the orientation of both types (filler and interfacial) of bonds in increasing the stiffness of structural composites. To the best of our knowledge, our study is the first to examine this effect on the mechanical properties of composites for nanofillers in this size range, thereby providing some unique mechanistic insights. We expect that these insights can be exploited to design polymer nanocomposites with optimized mechanical properties for a variety of applications.     

Quantitative Evaluation of the Antiischemic Effect of Isosorbide Dinitrate

The organic nitrates are widely used in thetreatment of coronary artery disease, not only inpatients with stable angina pectoris, unstable anginaand acute myocardial infraction, but also in themanagement of heart failure. However somecontroversial regarding the mechanisms of actionremains. Nitrates are generally thought to relax smoothmuscles which in peripheral vessels predominantly leadto venous dilatation with venous blood pooling andblood pressure reduction, and this in turn results inredu…