Efficient Phosphodiester Hydrolysis by Luminescent Terbium(III) and Europium(III) Complexes

The synthesis and structures of two new isostructural mononuclear [Ln(L)(NO(3))(H(2)O)(3)](NO(3))(2) complexes, with Ln = Tb (complex 1) and Eu (complex 2), which display high activity in the hydrolysis of the substrate 2,4-bis(dinitrophenyl)phosphate, are reported. These complexes displayed catalytic behavior similar to the mononuclear gadolinium complex [Gd(L)(NO(3))(H(2)O)(3)](NO(3))(2) previously reported by us (lnorg. Chem. 2008, 47, 2919-2921); one hydrolysis reaction in two stages where the diesterase and monoesterase activities could be monitored separately, with the first stage dependent on and the second independent of the complex concentration. Through potentiometric studies, electrospray ionization mass spectrometry (ESI-MS) analysis, and determination of the kinetic behaviors of 1 and 2 in acetonitrile/water solution, the species present in solution could be identified and suggested a dinuclear species, with one hydroxo group, as the most prominent catalyst under mild conditions. The complexes show high activity (k(1)= 7 and 18 s(-1) for 1 and 2, respectively) and catalytic efficiency. Complexes 1 and 2 were found to be active toward the cleavage of plasmid DNA, and complete kinetic studies were carried out. Studies with a radical scavenger (dimethylsulfoxide) confirmed the hydrolytic action of 1 and 2 in the cleavage of DNA. Studies on the incubation of distamycin with plasmid DNA suggested that 1 and 2 are regio-specific, interacting with the minor groove of DNA. These complexes displayed luminescent properties. Complex 1 showed higher emission intensity than 2 due to a more efficient energy transfer between triplet and emission levels of terbium (T -> (5)D(4)), along with nonradiative deactivation mechanisms of the excited states of europium via multiphonon decays and the ligand-to-metal charge transfer state. Lifetime measurements of the (5)D(4) and (5)D(0) excited levels for 1 and 2, respectively, indicated the numbers of coordinated water molecules for the complexes.

Biomimetic Oxidation of Piperine and Piplartine Catalyzed by Iron(III) and Manganese(III) Porphyrins

Synthetic metalloporphyrins, in the presence of monooxygen donors, are known to mimetize various reactions of cytochrome P450 enzymes systems in the oxidation of drugs and natural products. The oxidation of piperine and piplartine by iodosylbenzene using iron(III) and manganese(III) porphyrins yielded mono- and dihydroxylated products, respectively. Piplartine showed to be a more reactive substrate towards the catalysts tested. The structures of the oxidation products were proposed based on electrospray ionization tandem mass spectrometry.

Cyanocobalt(III) complexes of penta- and tetradentate-coordinated macrocyclic hexaamines

The pendent-arm macrocyclic hexaamine trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine (L) may coordinate in tetra-, penta- or hexadentate modes, depending on the metal ion and the synthetic procedure. We report here the crystal structures of two pseudo-octahedral cobalt(III) complexes of L, namely sodium trans-cyano(trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine)cobalt(III) triperchlorate, Na[Co(CN)(C13H30N6)](ClO4)(3) or Na{trans-[CoL(CN)]}(ClO4)(3), (I), where L is coordinated as a pentadentate ligand, and trans-dicyano(trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine) cobalt (III) trans-dicyano (trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diaminium)cobalt(III) tetraperchlorate tetrahydrate, [Co(CN)(2)(Cl4H32N6)][Co(CN)(2)(Cl4H30N6)](ClO4)(4)•-4H(2)O or trans-[CoL(CN)(2)]trans-[Co(H2L)(CN)(2)] (ClO4)(4)•-4H(2)O, (II), where the ligand binds in a tetradentate mode, with the remaining coordination sites being filled by C-bound cyano ligands. In (I), the secondary amine Co-N bond lengths lie within the range 1.944 (3)-1.969 (3) &ANGS;, while the trans influence of the cyano ligand lengthens the Co-N bond length of the coordinated primary amine [Co-N = 1.986 (3) &ANGS;]. The Co-CN bond length is 1.899 (3) &ANGS;. The complex cations in (11) are each located on centres of symmetry. The Co-N bond lengths in both cations are somewhat longer than in (I) and span a narrow range [1.972 (3)-1.982 (3) &ANGS;]. The two independent Co-CN bond lengths are similar [1.918 (4) and 1.926 (4) &ANGS;] but significantly longer than in the structure of (1), again a consequence of the trans influence of each cyano ligand.

Amphiphilic cerium(III) beta-diketonate as a catalyst for reducing diesel/biodiesel soot emissions

This work reports on the synthesis, characterization and applications of the new cerium(III) beta-diketonate Ce(hdacac)(3)(Hhdacac)(3)center dot 2H(2)O (where hdacac and Hhdacac denote, respectively, the hexadecylpentane-2,4-dionate and hexadecylpentane-2,4-dione ligands) as catalyst for the reduction of automotive emissions. Due to its amphiphilic character, this complex can be solubilized in non-polar fuels, thus generating cerium(IV) oxide particles, which efficiently catalyze the oxidation of diesel/biodiesel soot. The synthesized complex was characterized by microanalysis (C, H), thermal analysis, and infrared spectroscopy. Scanning electron microscopy, X-ray diffractometry, and specific surface area measurements attested that the complex can act as a soluble precursor of homogeneous CeO(2) spherical nanoparticles. The efficiency of this compound as catalyst for the reduction of soot emission was evaluated through static studies (comprising carbon black oxidation), which confirmed that increasing concentrations of the complex result in lower carbon black oxidation temperatures and lower activation Gibbs free energies. Dynamic studies, which embraced the combustion of diesel/biodiesel blends containing different amounts of the solubilized complex in a stationary motor, allowed a comparative evaluation of the soot emission through diffuse reflectance spectroscopy. These analyses provided very emphatic evidences of the efficiency of this new cerium complex for the control of soot emission in diesel/biodiesel motors. (c) 2009 Published by Elsevier B.V.

Highlights from the III International Symposium of Thrombosis and Anticoagulation (ISTA), October 14-16, 2010, Sao Paulo, Brazil

To discuss and share knowledge around advances in the care of patients with thrombotic disorders, the Third International Symposium of Thrombosis and Anticoagulation was held in So Paulo, Brazil, from October 14-16, 2010. This scientific program was developed by clinicians for clinicians, and was promoted by four major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, the Canadian VIGOUR Centre, and the Uppsala Clinical Research Center. Comprising 3 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia

Purpose Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose-and schedule-optimization study is reported. Patients and Methods In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1: 1: 1: 1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. Results With minimum follow-up of 6 months (median treatment duration, 8 months; range, = 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). Conclusion Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.

Idiopathic spinal epidural hematoma in patients with sudden paraplegia: A case report

Introduction. Spontaneous spinal epidural hematoma (SEH) represents 0.3-0.9% of spinal epidural space-occupying lesions, and most surgeons advocate aggressive and early surgical intervention. In. this paper we describe a patient with SEH with sudden paraplegia. Case report. This 30-year-old man had experienced one prior episode of sudden dorsal pain two days before the current admission and while he waited medical attendance, his legs suddenly became weak, and immediately afterwards, he became completely paraplegic in minutes. The patient had complete paraplegia, analgesia below the T4 level and urinary retention. He had no anticoagulant agent and no coagulopathic disease. He was submitted to computerized tomography that demonstrated a dorsally located epidural hematoma extending from the T3 to the T6 level with spinal cord compression. A laminectomy from T3 to T7 was performed four hours after the onset of the symptom. In postoperative time the patient presented the partial sensorial recovery and motor force grade II. The patient was directed to a neurorehabilitation program and in the last medical evaluation he presented recovery for motor grade III-IV without pain. Conclusion. The SHE is rare, with severe neurological consequences for patients and early surgical treatment persist as essential for motor recovery.

Overweight and obesity increase the risk of coronary heart disease: A pooled analysis of 30 prospective studies

The importance of overweight as a risk factor for coronary heart disease (CHD) remains unsettled. We estimated the relative risk (RR) for CHD associated with underweight (body mass index, BMI < 20 kg/m2), overweight (25 – 30 kg/m2) and obesity (= 30 kg/m2), compared with normal weight (20 – 25 kg/m2) in a random effects meta-analysis of 30 prospective studies, including 389,239 healthy, predominantly Caucasian persons. We also explored sources of heterogeneity between studies and examined effects of systematic adjustment for confounding and intermediary variables. Pooled age-, sex- and smoking-adjusted RRs (95% confidence interval) for overweight, obesity and underweight compared with normal weight were 1.33 (1.24 – 1.43), 1.69 (1.44 – 1.99) and 1.01 (0.85 – 1.20), respectively. Stratified analyses showed that pooled RRs for BMI were higher for studies with longer follow-up (= vs. < 15 years) and younger populations (< vs. = 60 years). Additional adjustment for blood pressure, cholesterol levels and physical activity decreased the RR per 5 BMI units from 1.28 (1.21 – 1.34) to 1.16 (1.11 – 1.21). We conclude that overweight and obesity are associated with a substantially increased CHD risk in Caucasians, whereas underweight is not. Prevention and reduction of overweight and obesity, therefore, remain of importance for preventing CHD.

Abatacept Improves Health-Related Quality of Life, Pain, Sleep Quality, and Daily Participation in Subjects With Juvenile Idiopathic Arthritis

Objective. To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA). Methods. In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to >= 1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined ""responders"") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children`s Sleep Habits Questionnaire, and a daily activity participation questionnaire. Results. A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents` usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents` usual activity days/month, respectively, in abatacept-versus placebo-treated subjects). Conclusion. Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.

A quantitative coronary angiography-matched comparison between a prospective randomised multicentre cutting balloon angioplasty and bare metal stent trial (REDUCE III) and the Rapamycin-Eluting Stent Evaluation At Rotterdam Cardiology Hospital (RESEARCH) study

Aims: There remains significant concern about the long-term safety of drug-eluting stents (DES). However, bare metal stents (BMS) have been used safely for over two decades. There is therefore a pressing need to explore alternative strategies for reducing restenosis with BMS. This study was designed to examine whether IVUS-guided cutting balloon angioplasty (CBA) with BMS could convey similar restenosis rates to DES. Methods and results: In the randomised REstenosis reDUction by Cutting balloon angioplasty Evaluation (REDUCE III) study, 521 patients were divided into four groups based on device and IVUS use before BMS (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At follow-up, the IVUS-CBA-BMS group had a significantly lower restenosis rate (6.6%) than the other groups (p=0.016). We performed a quantitative coronary angiography (QCA) based matched comparison between an IVUS-guided CBA-BMS strategy (REDUCE III) and a DES strategy (Rapamycin-Eluting-Stent Evaluation At Rotterdam Cardiology. Hospital, the RESEARCH study). We matched the presence of diabetes, vessel size, and lesion severity by QCA. Restenosis (>50% diameter stenosis at follow-up) and target vessel revascularisation (TVR) were examined. QCA-matched comparison resulted in 120-paired lesions. While acute gain was significantly greater in IVUS-CBA-BMS than DES (1.65 +/- 0.41 mm vs. 1.28 +/- 0.57 mm, p=0.001), late loss was significantly less with DES than with IVUS-CBA-BMS (0.03 +/- 0.42 mm vs. 0.80 +/- 0.47 mm, p=0.001). However, no difference was found in restenosis rates (IVUS-CBA-BMS: 6.6% vs. DES: 5.0%, p=0.582) and TVR (6.6% and 6.6%, respectively). Conclusions: An IVUS-guided CBA-BMS strategy yielded restenosis rates similar to those achieved by DES and provided an effective alternative to the use of DES.

Evaluation of molar teeth and buds in patients submitted to mandible distraction: Long-term results

Background: Despite all benefits offered by mandible distraction, complications and long-term consequences need to be evaluated to define its safety and morbidity. Forty mandible distractions were studied. Panoramic mandible radiographs obtained preoperatively, during distraction, and during the postoperative period were reviewed, with the intention of evaluating development and complications of molar buds and teeth in the distraction area. Methods: The mean patient age was 8.1 years. Twenty-five patients had craniofacial microsomia (one associated with a no. 10 facial cleft), five had temporomandibular joint ankylosis, two had familiar cases of auriculocondylar syndrome, one had a Tessier no. 30 facial cleft, and one had Treacher Collins syndrome. The severity of mandible hypoplasia was Pruzansky grade I in four cases, grade IIA in eight cases, grade 1113 in 16 cases, and grade III in one case. Mean radiographic follow-up was 44.8 months. Results: Molar buds located in the distraction area erupted without any deformity or displacement in 18 sides (45 percent). Fourteen cases presented distalization of a dental bud to a superior position in the mandibular ramus (four migrated back to the original position). Six molar buds presented perforations, four had shape deformities (two caused by dental fracture), and two had dental root injuries followed by root absorption lately. One case developed a dentigerous cyst. Conclusions: Almost half of the patients did not have any molar bud or tooth alterations after mandible distraction, and more than 20 percent presented only bud distalization. Therefore, preventive bud enucleation or tooth extraction should be avoided before mandible distraction.

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T 19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T 19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.

Is the ultrasound-estimated bladder weight a reliable method for evaluating bladder outlet obstruction?

OBJECTIVE To evaluate the correlation between ultrasound-estimated bladder weight (UEBW) in patients with different degrees of bladder outlet obstruction (BOO). METHODS We evaluated 50 consecutive non-neurogenic male patients with lower urinary tract symptoms (LUTS) referred to urodynamic study (UDS). All patients self-answered the International Prostate Score Symptoms (IPSS) questionnaire. After the UDS, the bladder was filled with 150 mL to determine UEBW. Patients with a bladder capacity under 150 mL, a previous history of prostate surgery or pelvic irradiation, an IPSS score <8, a bladder stone or urinary tract infection were excluded. After a pressure-flow study, the Schafer linear passive urethral resistance relation nomogram was plotted to determine the grade of obstruction: Grades I-II/VI were defined as mild obstruction, Grades III-IV/VI as moderate obstruction, and Grades V-VI/VI as severe obstruction. RESULTS The UEBW was 51.7 +/- 26.9, 54.1 +/- 30.0 and 54.8 +/- 28.2 in patients with mild, moderate and severe BOO, respectively (P = 0.130). The UEBW allowed us to define four groups: (i) UEBW < 35 g; (ii) 35 g <= UEBW < 50 g; (iii) 50 g <= UEBW < 70 g; and (4) UEBW >= 70 g. We did not find any differences in age, prostate weight, IPSS, PVR, cystometric bladder capacity, presence of detrusor overactive and degree of obstruction in the aforementioned groups. CONCLUSION Despite the fact that some studies have emphasized the value of UEBW as an efficient non-invasive method for evaluating lower urinary tract obstruction, our study suggests that UEBW does not present any individual correlation with LUTS or objective measurements of BOO.