Lidocaine dose-response effect on postoperative cognitive deficit: meta-analysis and meta-regression

Introduction: The true influence of the perioperative intravenous lidocaine on the development of postoperative cognitive deficit (POCD) in coronary artery bypass grafting (CABG) remains controversial. The principal aim is to undertake a meta-regression to determine whether moderator variables mediate the relationship between lidocaine and POCD.

Areas covered: We searched the Web of Science, PubMed database, Scopus and the Cochrane Library database (up to June 2017) and systematically reviewed a list of retrieved articles. Our final review includes only randomized controlled trials (RCTs) that compared infusion of lidocaine and placebo during cardiopulmonary bypass (CPB). Mantel–Haenszel risk ratio (MH RR) and corresponding 95% confidence interval (CI) was used to report the overall effect and meta-regression analysis. A total of 688 patients in five RCTs were included. POCD occurred in 34% of all cases. Perioperative lidocaine reduces POCD (MH RR 0.702 (95% CI: 0.541–0.909). Younger age, male gender, longer CPB and higher concentration of lidocaine significantly mediate the relationship between lidocaine and POCD in favour of the neuroprotective effect of lidocaine.

Expert commentary: The neuroprotective effect of lidocaine on POCD is consistent in spite of longer CPB time. A higher concentration of lidocaine strengthened the neuroprotective effect of lidocaine.     

Application of PC-SAFT EOS for Pharmaceuticals: Solubility,Co-Crystal,and Thermodynamic Modeling

In this study, the applicability of the perturbed chain statistical associating fluid theory (PC-SAFT) was evaluated for pharmaceutical compounds. For this purpose, the parameters of the PC-SAFT equation of state (EOS) were regressed by applying the experimental solubility data of 54 pharmaceuticals in pure solvents. The reported errors for train and test data show the suitability of the PC-SAFT EOS. The applicability of the PC-SAFT EOS was explored by its prediction accuracy for the ternary system of medicine in solvent mixtures. The model errors were 23 and 26% for two ternary systems of salicylic acid and lidocaine HCl in solvent mixtures of ethanol and water, respectively. The co-crystal formation of salicylic acid-sulfamethazine in methanol was investigated by the PC-SAFT EOS. Finally, the reaction and crystallization sections for acetaminophen production from p-aminophenol were simulated by accompanying the PC-SAFT EOS and equilibrium assumption. The purification efficiencies for acetaminophen were obtained to be 93–98% for different temperatures.     

Induction of G1 cell cycle arrest and cyclin D1 down-regulation in response to pericarp extract of Baneh in human breast cancer T47D cells

Background and the purpose of the study

Natural products from plants have an important role in the development and production of new drugs mainly for cancer therapy. More recently, we have shown that the pericarp methanolic extract of Pistacia atlantica sub kurdica (with local name of Baneh) as a rich source of active biological components with high antioxidant and radical scavenging activities, has ability to cease proliferation and induce apoptosis in T47D human breast cancer cells. The present study aimed to clarify whether Baneh extract able to alter cell cycle progression of T47D cells or not.

Methods

In order to study the possible effect of Baneh extract on cell cycle of T47D cells, we evaluated cell cycle distribution and its regulatory proteins by flow cytometry and western blot analysis respectively.

Results

Baneh extract induced G₀/G₁ cell cycle arrest in conjunction with a marked decrease in expression of cyclin D1 and cdk4 that was strongly dependent on time of exposure. In parallel, Dox-treated T47D cells in early time points were accumulated on S phase, but after 48 h cell cycle progression was inhibited on G₂/M. Dox promoted striking accumulation of cyclin B1 rapidly and enhanced cyclin A abundance.

Conclusion

Taken together, our results establish that the antitumor activity of the pericarp extract of Baneh partly is mediated via cell cycle arrest and downregulation of cyclin D1 and cdk4 expression. These findings warrant further evaluation regarding the mechanism(s) of action of this promising anticancer agent.     

Topical Silymarin Administration for Prevention of Capecitabine‐Induced Hand–Foot Syndrome: A Randomized,Double‐Blinded,Placebo‐Controlled Clinical Trial

Hand–foot syndrome (HFS) is a frequent dose‐limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine‐induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9^th week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine‐induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.     

Protective effects of lycopene and tomato extract against doxorubicin-induced cardiotoxicity

The protective effect of tomato extract and lycopene on acute doxorubicin (DOX) myocardial toxicity was evaluated in mice. DOX toxicity, induced by a single intraperitoneal injection (15 mg/kg), was revealed by an elevated serum CPK(MB) and histopathological observations. Tomato extract (1.2 and 2.4 g/kg, i.p.) and lycopene (1.7 and 3.5 mg/kg, i.p.) prevented the rise in serum CPK(MB) and ameliorated cardiac cell injury. These results suggest that tomato extract and lycopene inhibit DOX cardiotoxicity and might serve as a novel combination chemotherapeutic agent with DOX to limit free radical-mediated organ injury.     

Effect of peptide length on the conjugation to the gold nanoparticle surface: a molecular dynamic study

Background

Gold nanoparticles now command a great deal of attention for medical applications. Despite the importance of nano-bio interfaces, interaction between peptides and proteins with gold surfaces is not still fully understood, especially in a molecular level.

Methods

In the present study computational simulation of adsorption of 20 amino acids, in three forms of mono-amino acid, homo di-peptide and homo tri-peptide, on the gold nanoparticles was performed by Gromacs using OPLSAA force field. The flexibility, stability, and size effect of the peptides on the gold nanoparticles were studied as well as the molecular structure of them.

Results

According to our results, adsorbed homo tri-peptides on the gold surface had more flexibility, more gyration, and the farthest distance from the GNP in comparison with homo di-peptides and mono-amino acids.

Conclusion

Our findings provide new insights into the precise control of interactions between amino acids anchored on the GNPs.

     

Inhibitory effects of Zataria multiflora essential oil and its main components on nitric oxide and hydrogen peroxide production in glucose-stimulated human monocyte

The inhibitory effects of Zataria multiflora essential oil on nitric oxide (NO) and hydrogen peroxide (H₂O₂) production were examined in human monocytes cultured in the presence of 20 mM glucose. Z. multiflora essential oil was extracted by water-distillation and then analyzed by GC–MS. Carvacrol (29.2%), thymol (25.4%), p-cymene (11.2%), linalool (9.6%) and γ-terpinene (8%) were the main components detected in the essential oil. Cells cultured in the presence of 20 mM glucose showed an increase in NO and H₂O₂ production as well as NO synthase (NOS) and NADH oxidase (NOX) activities compared to cells cultured in the presence of 5 mM glucose. Pretreatment with Z. multiflora essential oil, carvacrol and thymol reduced NO and H₂O₂ production as well as NOS and NOX activities in those cells cultured in the presence of 20 mM glucose. However, p-cymene, linalool and γ-terpinene did not show any such activities. Accordingly, it was concluded that Z. multiflora can reduce oxidative stress and can be used in the therapy of oxidative damage accompanying hyperglycemia and some inflammatory conditions.     

The prevalence of obesity and its related risk factor in the north of iran in 2006

Background: The main objective of this study was to evaluate the prevalence of the obesity and the related risk factors in the north of Iran. Methods: This was a population-based cross-sectional study that enrolled 2495 subjects (1247 males and 1248 females) using stratified cluster sampling. Interviewers recorded the data using a multidimensional questionnaire including anthropometric indexes. Body mass index equal to or greater than 25 was considered as overweight and that of 30 and 40 as obese and pathologic obese respectively. SPSS 16.0 software was used for statistical data analysis. Results: Mean age of the subjects was 39.2 [95% CI: 38.6, 39.8] yr. Mean body mass index was 25.3 [95% CI: 25.0, 25.6] kg/m(2) for men and 27.5 [95% CI: 27.2, 27.9] kg/m2 for women. The prevalence rates of overweight, obesity and pathologic obesity were 29.9% (745/2495), 22.5% (561/2495) and 1.8% (44/2495) respectively. The prevalence of obesity was higher in urban residents than rural ones, 27.3% versus 18.9% respectively (P<0.001). The prevalence rates of obesity and pathologic obesity were much higher in women than men were, 30.3% versus 15.4% and 3.0% versus 0.6% respectively (P=0.001). The odds ratio estimate was 1.68 [95% CI: 1.40, 2.02] for urban area compared to rural area; 2.60 [95% CI: 2.14, 3.15] for females compared to males; 5.95 [95% CI: 3.54, 9.99] for married people compared to single people; 1.89 [95% CI: 1.44, 2.84] for age group of 55-65 years compared to age group of 15-24 years; 1.76 [95% CI: 1.17, 2.64] for illiterate people compared to those who had academic education; 1.98 [95% CI: 1.13, 2.49] for poor people compared to people with high economic level. Conclusion: The prevalence of obesity and overweight is very high in the north of Iran, hence is a signal of serious health problem, and should be the focus of special attention.     

传统与欠矫手术治疗部分调节性内斜视的比较

目的：评估传统与欠矫手术治疗部分调节性内斜视患者的效果。 方法：将25例具有部分调节性内斜视和正常AC／A的患者随机分为两组，其中13例患者接受传统手术治疗，其余12例患者接受欠矫手术治疗。传统手术是基于远距远视完全矫正所测量的偏差上，而欠矫手术比传统手术标准低20％。所有患者均进行对称性双眼内直肌后退术，术后随访6mo。 结果：术后6mo，传统组与欠矫组手术成功率分别为46％和91％（成功标准定义为通过近距和远距远视的完全矫正斜视≤8^△）。传统组和欠矫组的手术过矫率分别为54％和9％，两组间差异有统计学意义（P〈0．05）。没有残余内斜视。手术成功率或欠矫率与患者的年龄、术前等效球镜均值、术前眼偏斜量无相关性。 结论：对于具有正常AC／A的部分调节性内斜视患者，欠矫的双眼内直肌后退术成功率较高，过矫率较低。     

The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats

Objective

This study was performed to evaluate the effect of pregabalin co-administration with vitamin E in Partial Sciatic Nerve Ligation (PSNL)-induced neuropathic pain in rats.

Methods

Male Wistar rats were randomly allocated as control, sham, and PSNL groups (n = 8). PSNL was induced by tight ligation of the sciatic nerve with a copper wire. On day 14th, the PSNL and sham operated rats received either pregabalin (1, 3, and 30 mg/kg), vitamin E (100 and 200 mg/kg), or their combination intraperitoneally. An antinociceptive effect was evaluated as latency times and Maximum possible Effect Percent (%MPE) using tail-flick test. Locomotor activity was evaluated by open-field test before PSNL surgery and then twice at the 14th days (before and after drug injection). Ligated nerves were removed on the 28th days after surgery for histological examinations.

Results

The time course of latency times and %MPE showed significant decrease in PSNL but not in sham and control groups. Pregabalin (3 and 30 mg/kg) and vitamin E (100 and 200 mg/kg) caused significant increases in latency time in PSNL (but not sham) group compared to control group. Vitamin E 200 mg/kg increased significantly %MPE in PSNL group compared to sham group. In addition, the %MPE following combination treatment of pregabalin (30 mg/kg) and vitamin E (100 mg/kg) was significantly higher than both vitamin E and control group. Also combination of pregabalin with 100 mg/kg of vitamin E reversed Wallerian degeneration of sciatic nerve and the inflammatory responses to almost similar to sham group. Pregabalin and vitamin E did not affect locomotor activity.

Conclusion

Our results showed antinociceptive effects of both vitamin E and pregabalin alone or in combination in PSNL rats and also neuroprotective properties without affecting locomotor activity.