Analgesic and Anti-Inflammatory Activities of Salicylaldehyde 2-Chlorobenzoyl Hydrazone (H(2)LASSBio-466), Salicylaldehyde 4-Chlorobenzoyl Hydrazone (H(2)LASSBio-1064) and Their Zinc(II) Complexes

Salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their complexes [Zn(LASSBio-466) H(2)O](2) (1) and [Zn(HLASSBio-1064) Cl](2) (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the anti-nociceptive activity was favored in the complex 1. H(2)LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H(2)LASSBio-466. H(2)LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.

cis-Bis[1,1-dibenzyl-3-(furan-2-ylcarbonyl)thioureato-kappa(2)O,S]copper(II)

In the title compound, [Cu(C(20)H(17)N(2)O(2)S)(2)], the Cu(II) atom is coordinated by the S and O atoms of two 1,1-dibenzyl-3-(furan-2-ylcarbonyl)thioureate ligands in a distorted square-planar geometry. The two O and two S atoms are mutually cis to each other. The Cu-S and Cu-O bond lengths lie within the ranges of those found in related structures. The dihedral angle between the planes of the two chelating rings is 26.15 (6)degrees.

cis-Bis[N-(2-furoyl)-N ',N '-diphenylthioureato-kappa(2)O,S]nickel(II)

In the title compound, [Ni(C(18)H(13)N(2)O(2)S)(2)], the Ni(II) atom is coordinated by the S and O atoms of two N-furoyl-N ',N '-diphenylthioureate ligands in a slightly distorted squareplanar coordination geometry. The two O and two S atoms are cis to each other.

cis-bis(N-benzoyl-N ',N '-dibenzylthio-ureato-kappa O-2,S)nickel(II)

In the title compound, [Ni(C22H19N2OS)(2)], the Ni-II atom is coordinated by the S and O atoms of two N-benzoyl-N',N'-dibenzylthioureate ligands in a slightly distorted square-planar geometry. The two O atoms are cis, as are the two S atoms.

Quantification of some nonsteroidal anti-inflammatory drugs as reducing agents of Cu(II)/4,4 '-dicarboxy-2,2 '-biquinoline complexes in cationic micellar medium

A simple method was developed for spectrophotometric determination of some nonsteroidal anti-inflammatory drugs (meloxicam, piroxicam and tenoxicam) based on the reduction of copper(II) in buffered solution (pH 7.0) and micellar medium containing 4,4'-dicarboxy-2,2'-buffered solution (pH 7.0) and micellar medium containing 4,4'-dicarboxy-2,2'-biquinoline acid. The-biquinoline acid. The absorbance values at 558 nm, characteristic of the formed Cu(I)/4,4'-dicarboxy-2,2'-biquinoline complexes, are linear with the concentrations (5.7-40 mmol L(-1), n = 5) of these oxicams (meloxicam r = 0.998; piroxicam and tenoxicam r = 0.999). The limit of detection values, in mmol L(-1), calculated for meloxicam (2.7), piroxicam (1.2) and tenoxicam (1.3) was obtained with 99% confidence level and the relative standard deviations for meloxicam (3.1%), piroxicam (5.1%) and tenoxicam (1.2%) were calculated using a 25 mmol L(-1) solution (n = 7). Mean recovery values for meloxicam, piroxicam and tenoxicam forms were 100 +/- 6.9, 98.6 +/- 3.6 and 99.4 +/- 2.5%, respectively. The conditional potential of Cu(II)/Cu(I) in complex medium of 7.5 mmol L(-1) BCA was determined to be 629 +/- 11 mV vs. NHE.

Consecutive biocatalysis-palladium catalysis II: Synthesis of conduritol-alkyne conjugates

The palladium-catalyzed cross-coupling reaction of potassium alkynyltrifluoroborates with a chemoenzymatically derived deoxyconduritol is described. Six new compounds were synthesized in moderate to good yields. The alkynyl cross-coupling reaction can be effected using 10 mol% of Pd(PPh(3))(4) as Catalyst in toluene-H(2)O in the presence Of Cs(2)CO(3) as the inorganic base. (C) 2009 Elsevier B.V. All rights reserved.

Aerobic Exercise Training-Induced Left Ventricular Hypertrophy Involves Regulatory MicroRNAs, Decreased Angiotensin-Converting Enzyme-Angiotensin II, and Synergistic Regulation of Angiotensin-Converting Enzyme 2-Angiotensin (1-7)

Aerobic exercise training leads to a physiological, nonpathological left ventricular hypertrophy; however, the underlying biochemical and molecular mechanisms of physiological left ventricular hypertrophy are unknown. The role of microRNAs regulating the classic and the novel cardiac renin-angiotensin (Ang) system was studied in trained rats assigned to 3 groups: (1) sedentary; (2) swimming trained with protocol 1 (T1, moderate-volume training); and (3) protocol 2 (T2, high-volume training). Cardiac Ang I levels, Ang-converting enzyme (ACE) activity, and protein expression, as well as Ang II levels, were lower in T1 and T2; however, Ang II type 1 receptor mRNA levels (69% in T1 and 99% in T2) and protein expression (240% in T1 and 300% in T2) increased after training. Ang II type 2 receptor mRNA levels (220%) and protein expression (332%) were shown to be increased in T2. In addition, T1 and T2 were shown to increase ACE2 activity and protein expression and Ang (1-7) levels in the heart. Exercise increased microRNA-27a and 27b, targeting ACE and decreasing microRNA-143 targeting ACE2 in the heart. Left ventricular hypertrophy induced by aerobic training involves microRNA regulation and an increase in cardiac Ang II type 1 receptor without the participation of Ang II. Parallel to this, an increase in ACE2, Ang (1-7), and Ang II type 2 receptor in the heart by exercise suggests that this nonclassic cardiac renin-angiotensin system counteracts the classic cardiac renin-angiotensin system. These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, altering the expression of specific microRNAs targeting renin-angiotensin system genes. Together these effects might provide the additional aerobic capacity required by the exercised heart. (Hypertension. 2011;58:182-189.).

Phase II Trial of Infusional Fluorouracil, Irinotecan, and Bevacizumab for Metastatic Colorectal Cancer: Efficacy and Circulating Angiogenic Biomarkers Associated With Therapeutic Resistance

Purpose We investigated the efficacy of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in a phase II trial in patients previously untreated for metastatic colorectal cancer (mCRC), and changes during treatment in plasma cytokines and angiogenic factors (CAFs) as potential markers of treatment response and therapeutic resistance. Patients and Methods We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m(2)), bolus FU (400 mg/m(2)), and leucovorin (400 mg/m(2)) followed by a 46-hour infusion of FU (2,400 mg/m(2)). Levels of 37 CAFs were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, during treatment, and at the time of progressive disease (PD). Results Forty-three patients were enrolled. Median progression-free survival (PFS), the primary end point of the study, was 12.8 months. Median overall survival was 31.3 months, with a response rate of 65%. Elevated interleukin-8 at baseline was associated with a shorter PFS (11 v 15.1 months, P = .03). Before the radiographic development of PD, several CAFs associated with angiogenesis and myeloid recruitment increased compared to baseline, including basic fibroblast growth factor (P = .046), hepatocyte growth factor (P = .046), placental growth factor (P < .001), stromal-derived factor-1 (P = .04), and macrophage chemoattractant protein-3 (P < .001). Conclusion Efficacy and tolerability of FOLFIRI + B appeared favorable to historical controls in this single arm study. Before radiographic progression, there was a shift in balance of CAFs, with a rise in alternate pro-angiogenic cytokines and myeloid recruitment factors in subsets of patients that may represent mechanisms of resistance.

Impact of metabolic syndrome on the outcome of patients with stable coronary artery disease: 2-year follow-up of the MASS II study

Objective We characterized the impact of the metabolic syndrome (MetS) and its components on cardiovascular adverse events in patients with symptomatic chronic multivessel coronary artery disease, which have been followed prospectively for 2 years. Methods Patients enrolled in the MASS II study were evaluated for each component of the MetS, as well as the full syndrome. Results The criteria for MetS were fulfilled in 52% of patients. The presence of MetS (P < 0.05), glucose intolerance (P=0.007), and diabetes (P=0.04) was associated with an increased mortality in our studied population. Moreover, despite a clear tendency for each of its components to increase the mortality risk, only the presence of the MetS significantly increased the risk of mortality among nondiabetic study participants in a multivariate model (P=0.03, relative risk 3.5, 95% confidence interval 1.1-6). Finally, MetS was still associated with increased mortality even after adjustment for diabetes status. These results indicate a strong and consistent relationship of the MetS with mortality in patients with stable coronary artery disease. Conclusion Although glucose homeostasis seems to be the major force driving the increased risk of MetS, the operational diagnosis of MetS still has information for stratifying patients when diabetes information is taken into account.

Angiotensin-converting enzyme inhibition augments the expression of rat elastase-2, an angiotensin II-forming enzyme

Becari C, Teixeira FR, Oliveira EB, Salgado MC. Angiotensin-converting enzyme inhibition augments the expression of rat elastase- 2, an angiotensin II-forming enzyme. Am J Physiol Heart Circ Physiol 301: H565-H570, 2011. First published May 20, 2011; doi:10.1152/ajpheart.00534.2010.-Mounting evidence suggest that tissue levels of angiotensin (ANG) II are maintained in animals submitted to chronic angiotensin-converting enzyme (ACE) inhibitor treatment. We examined the expression levels of transcripts for elastase-2, a chymostatin-sensitive serine protease identified as the alternative pathway for ANG II generation from ANG I in the rat vascular tissue and the relative role of ACE-dependent and -independent pathways in generating ANG II in the rat isolated carotid artery rings of spontaneously hypertensive rats (SHR) and Wistar normotensive rats (WNR) treated with enalapril for 7 days. Enalapril treatment decreased blood pressure of SHR only and resulted in significantly more elastase-2 mRNA expression in carotid artery of both enalapril-treated WNR and SHR. Captopril induced a comparable rightward shift of concentration-response curves to ANG I in vehicle and enalapril-treated rats, although this effect was of lesser magnitude in SHR group. Chymostatin induced a rightward shift of the dose response to ANG I in vehicle-treated and a decrease in maximal effect of 22% in enalapril-treated WNR group. Maximal response induced by ANG I was remarkably reduced by chymostatin in enalapril-treated SHR carotid artery (by 80%) compared with controls (by 23%). Our data show that chronic ACE inhibition was associated with augmented functional role of non-ACE pathway in generating ANG II and increased elastase-2 gene expression, suggesting that this protease may contribute as an alternative pathway for ANG II generation when ACE is inhibited in the rat vascular tissue.

Treatment stability in patients with Class II malocclusion treated with 2 maxillary premolar extractions or without extractions

Introduction: The purpose of this study was to compare the occlusal stability of Class II malocclusion treatment with and without extraction of 2 maxillary premolars. Methods: A sample of 59 records from patients with complete Class II malocclusion was used. This sample was divided into 2 groups with the following characteristics: group 1, comprising 29 patients treated without extractions, and group 2, comprising 30 patients treated with extraction of 2 maxillary premolars. Dental cast measurements were obtained before and after treatment and at a minimum of 2.4 years after treatment. The pretreatment, posttreatment, and postretention occlusal statuses were evaluated with the peer assesment rating index. The occlusal indexes at the postretention stage and the posttreatment changes and percentages of posttreatment changes were compared with t tests. Results: The nonextraction and the 2 maxillary premolar extraction treatment protocols of complete Class II malocclusions had no statistically significant differences in occlusal stability. Conclusions: Finishing Class II malocclusion treatment with the molars in a Class II relationship has similar occlusal stability as finishing with the molars in a Class I relationship. (Am J Orthod Dentofacial Orthop 2010;138:16-22)

Tooth-wear patterns in adolescents with normal occlusion and Class II Division 2 malocclusion

Introduction: In this study, we investigated tooth-wear patterns in adolescents with either normal occlusion or Class II Division 2 malocclusion. Methods: The sample consisted of dental casts from 165 subjects that were divided into 2 groups: 115 normal occlusion subjects (mean age, 14.3 years) and 50 complete Class II Division 2 subjects (mean age, 13.9 years). Dental wear was assessed by using a modified version of the tooth wear index. The 2 groups were compared with the Mann-Whitney test for the frequency and severity of wear on each surface of each group of teeth. The level of statistical significance was set at 5%. Results: The normal occlusion group statistically had greater tooth wear on the incisal surfaces of the maxillary lateral incisors and the incisal surfaces of the maxillary canines than did the Class II Division 2 malocclusion group. The malocclusion group showed statistically greater tooth wear on the labial surfaces of the mandibular lateral incisors, the occlusal surfaces of the maxillary premolars and first molars, the occlusal surfaces of the mandibular premolars, the palatal surfaces of the maxillary second premolars, and the buccal surfaces of the mandibular premolars and first molars than did the normal occlusion group. Conclusions: Subjects with normal occlusion and those with complete Class II Division 2 malocclusions have different tooth-wear patterns. Tooth wear on the malocclusion subjects should not be considered pathologic but, rather, the consequence of different interocclusal arrangements. (Am J Orthod Dentofacial Orthop 2010;137:730.e1-730.e5)

Effects of the pendulum appliance, cervical headgear, and 2 premolar extractions followed by fixed appliances in patients with Class II malocclusion

Introduction: In this retrospective study, we compared the cephalometric effects, the dental-arch changes, and the efficiency of Class II treatment with the pendulum appliance, cervical headgear, or extraction of 2 maxillary premolars, all associated with fixed appliance therapy. Methods: The sample of 82 patients with Class II malocclusion was divided into 3 groups: group 1 patients (n = 22; treatment time, 3.8 years) were treated with the pendulum appliance and fixed orthodontic appliances. Group 2 patients (n = 30; treatment time, 3.2 years) were treated with cervical headgear followed by fixed appliances; group 3 patients (n = 30; treatment time, 2.1 years) were treated with 2 maxillary premolar extractions and fixed appliances. The average starting ages of the groups ranged from 13.2 to 13.8 years. Data were obtained from serial cephalometric measurements and dental casts. The dental casts were analyzed with the treatment priority index. The treatment efficiency index was also used. Results: The 3 treatment protocols produced similar cephalometric effects, especially skeletally. Comparisons among the 2 distalizing appliances (pendulum and cervical headgear) and extraction of 2 maxillary premolars for Class II treatment showed changes primarily in the maxillary dentoalveolar component and dental relationships. The facial profile was similar after treatment, except for slightly more retrusion of the upper lip in the extraction patients. The treatment priority index demonstrated that occlusal outcomes also were similar among the groups. The treatment efficiency index had higher values for the extraction group. Conclusions: The effects of treatment with the pendulum appliance or cervical headgear and extraction of 2 maxillary premolars associated with fixed appliances were similar from both occlusal and cephalometric standpoints. Class II treatment with extraction of maxillary teeth was more efficient because of the shorter treatment time. Differences in maxillary incisor retraction should be noted, but these differences might have been due to greater maxillary dentoalveolar protrusion in the extraction group before treatment. (Am J Orthod Dentofacial Orthop 2009;136:833-42)

Long-term stability of Class II malocclusion treated with 2-and 4-premolar extraction protocols

Introduction: The objective of this study was to cephalometrically compare the stability of complete Class II malocclusion treatment with 2 or 4 premolar extractions after a mean period of 9.35 years. Methods: A sample of 57 records from patients with complete Class II malocclusion was selected and divided into 2 groups. Group 1 consisted of 30 patients with an initial mean age of 12.87 years treated with extraction of 2 maxillary premolars. Group 2 consisted of 27 patients with an initial mean age of 13.72 years treated with extraction of 4 premolars. T tests were used to compare the groups` initial cephalometric characteristics and posttreatment changes. Pearson correlation coefficients were calculated to determine the correlation between treatment and posttreatment dental-relationship changes. Results: During the posttreatment period, both groups had similar behavior, except that group 1 had a statistically greater maxillary forward displacement and a greater increase in the apical-base relationship than group 2. On the other hand, group 2 had a statistically greater molar-relationship relapse toward Class II. There were significant positive correlations between the amounts of treatment and posttreatment dentoalveolar-relationship changes. Conclusions: Treatment of complete Class II malocclusions with 2 maxillary premolar extractions or 4 premolar extractions had similar long-term posttreatment stability. (Am J Orthod Dentofacial Orthop 2009;136:154.e1-154.e10)

Influence of cephalometric characteristics on the occlusal success rate of Class II malocclusions treated with 2-and 4-premolar extraction protocols

Introduction: The objectives of this investigation were to compare the initial cephalometric characteristics of complete Class II Division 1 malocclusions treated with 2 or 4 premolar extractions and to verify their influence on the occlusal success rate of these treatment protocols. Methods: A sample of 98 records from patients with complete Class II Division 1 malocclusion was divided into 2 groups with the following characteristics: group 1 consisted of 55 patients treated with 2 maxillary first premolar extractions at an initial mean age of 13.07 years; group 2 included 43 patients treated with 4 premolar extractions, with an initial mean age of 12.92 years. Initial and final occlusal statuses were evaluated on dental casts with Grainger`s treatment priority index (TPI), and the initial cephalometric characteristics were obtained from the pretreatment cephalograms. The initial cephalometric characteristics and the initial and final occlusal statuses of the groups were compared with the t test. A multiple regression analysis was used to evaluate the influence of all variables in the final TPI. Results: The 2-premolar extraction protocol provided a statistically smaller TPI and consequently a better occlusal success rate than the 4-premolar extraction protocol. The 4-premolar extraction group had statistically smaller apical base lengths, more vertical facial growth patterns, and greater hard- and soft-tissue convexities at pretreatment than the 2-premolar extraction group. However, the multiple regression analysis showed that only the extraction protocol was significantly associated with the final occlusal status. Conclusions: The initial cephalometric characteristics of the groups did not influence the occlusal success rate of these 2 treatment protocols.