A tetra-nuclear nickel(II) complex, [Ni4(L)4](ClO4)4·C2H3N·2H2O, with an asymmetric Ni4O4 open-cubane-like core.

A tetra-nuclear complex with an open-cubane-like core structure was synthesized from 2-meth-oxy-6-(pyridin-2-yl-hydrazonometh-yl)phenol (HL), namely, cyclo-tetra-kis-(µ-2-meth-oxy-6-{[2-(pyridin-2-yl)hydrazin-1-yl-idene]meth-yl}pheno-lato)tetra-nickel(II) tetra-kis-(perchlorate) aceto-nitrile monosolvate dihydrate, [Ni4(C13H12N3O2)4](ClO4)4·C2H3N·2H2O, and characterized using micro-analytical and spectroscopic techniques. The crystal-structure determination reveals the formation of a distorted Ni4O4 cubane-like core architecture encapsulated by four hydrazone Schiff base (HL) mol-ecules. A open-cube tetra-nuclear architecture is created in which nickel(II) ions of the NiN2O3 unit are connected by µ2-O anions of the phenolate moiety of HL. In this complex, each Ni centre has a slightly distorted square-pyramidal coordination environment. The supra-molecular architectures are stabilized via the presence of various inter-molecular hydrogen bonds and (ar-yl-aryl, ar-yl-chelate and chelate-chelate) stacking inter-actions.

In vitro and in vivo characterization of the multiple isoforms of Schistosoma mansoni hypoxanthine-guanine phosphoribosyltransferases.

Schistosoma mansoni, the parasite responsible for schistosomiasis, lacks the "de novo" purine biosynthetic pathway and depends entirely on the purine salvage pathway for the supply of purines. Numerous reports of praziquantel resistance have been described, as well as stimulated efforts to develop new drugs against schistosomiasis. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine salvage pathway. Here, we describe a crystallographic structure of the S. mansoni HPGRT-1 (SmHGPRT), complexed with IMP at a resolution of 2.8 Ǻ. Four substitutions were identified in the region of the active site between SmHGPRT-1 and human HGPRT. We also present data from RNA-Seq and WISH, suggesting that some isoforms of HGPRT might be involved in the process related to sexual maturation and reproduction in worms; furthermore, its enzymatic assays show that the isoform SmHGPRT-3 does not present the same catalytic efficiency as other isoforms. Finally, although other studies have previously suggested this enzyme as a potential antischistosomal chemotherapy target, the kinetics parameters reveal the impossibility to use SmHGPRT as an efficient chemotherapeutic target.

Structural and kinetic analysis of Schistosoma mansoni Adenylosuccinate Lyase (SmADSL).

Schistosoma mansoni is the parasite responsible for schistosomiasis, a disease that affects about 218 million people worldwide. Currently, both direct treatment and disease control initiatives rely on chemotherapy using a single drug, praziquantel. Concerns over the possibility of resistance developing to praziquantel, have stimulated efforts to develop new drugs for the treatment of schistosomiasis. Schistosomes do not have the de novo purine biosynthetic pathway, and instead depend entirely on the purine salvage pathway to supply its need for purines. The purine salvage pathway has been reported as a potential target for developing new drugs against schistosomiasis. Adenylosuccinate lyase (SmADSL) is an enzyme in this pathway, which cleaves adenylosuccinate (ADS) into adenosine 5'-monophosphate (AMP) and fumarate. SmADSL kinetic characterization was performed by isothermal titration calorimetry (ITC) using both ADS and SAICAR as substrates. Structures of SmADSL in Apo form and in complex with AMP were elucidated by x-ray crystallography revealing a highly conserved tetrameric structure required for their function since the active sites are formed from residues of three different subunits. The active sites are also highly conserved between species and it is difficult to identify a potent species-specific inhibitor for the development of new therapeutic agents. In contrast, several mutagenesis studies have demonstrated the importance of dimeric interface residues in the stability of the quaternary structure of the enzyme. The lower conservation of these residues between SmADSL and human ADSL could be used to lead the development of anti-schistosomiasis drugs based on disruption of subunit interfaces. These structures and kinetics data add another layer of information to Schistosoma mansoni purine salvage pathway.

Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations.

RATIONALE: Frequent chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation. Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations. OBJECTIVES: To determine whether regular therapy with macrolides reduces exacerbation frequency. METHODS: We performed a randomized, double-blind, placebo-controlled study of erythromycin administered at 250 mg twice daily to patients with COPD over 12 months, with primary outcome variable being the number of moderate and/or severe exacerbations (treated with systemic steroids, treated with antibiotics, or hospitalized). MEASUREMENTS AND MAIN RESULTS: We randomized 109 outpatients: 69 (63%) males, 52 (48%) current smokers, mean (SD) age 67.2 (8.6) years, FEV1 1.32 (0.53) L, FEV1% predicted 50 (18)%. Thirty-eight (35%) of the patients had three or more exacerbations in the year before recruitment, with no differences between treatment groups. There were a total of 206 moderate to severe exacerbations: 125 occurred in the placebo arm. Ten in the placebo group and nine in the macrolide group withdrew. Generalized linear modeling showed that the rate ratio for exacerbations for the macrolide-treated patients compared with placebo-treated patients was 0.648 (95% confidence interval: 0.489, 0.859; P = 0.003) and that these patients had shorter duration exacerbations compared with placebo. There were no differences between the macrolide and placebo arms in terms of stable FEV1, sputum IL-6, IL-8, myeloperoxidase, bacterial flora, serum C-reactive protein, or serum IL-6 or in changes in these parameters from baseline to first exacerbation over the 1-year study period. CONCLUSIONS: Macrolide therapy was associated with a significant reduction in exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this important patient population. Clinical trial registered with www.clinicaltrials.gov (NCT 00147667).

Adult Plant Evaluation of Soybean Accessions for Resistance to Phakopsora pachyrhizi in the Field and Greenhouse in Paraguay.

Five hundred thirty soybean accessions from maturity groups (MG) III through IX were evaluated for resistance to Phakopsora pachyrhizi in a replicated field trial at Centro Regional de Investigación Agrícola in Capitán Miranda, Itapúa, Paraguay during the 2005-06 season. Soybean rust severities of individual accessions ranged from 0% (resistant) to 30.0% (susceptible). In MG III and IV, the most resistant accessions were PI 506863, PI 567341, and PI 567351B, with severities less than 1.2%. In MG V, the most resistant accessions were PI 181456, PI 398288, PI 404134B, and PI 507305, with severities less than 0.3%. In MG VI, the most resistant accessions were PI 587886, PI 587880A, and PI 587880B, with severities less than 0.3%. In MG VII and VIII, the most resistant were PI 587905 and PI 605779E, with severities less than 1.0%. In MG IX, the most resistant accessions were PI 594754, PI 605833, PI 576102B, and PI 567104B, with severities less than 1.0%. The resistance in 10 selected accessions from MG VI, VII, VIII, and XI was confirmed in subsequent greenhouse and field experiments where severities of 0.4% or less and reddish-brown lesions with sporulation levels less than 3.0 were observed. These accessions, with low severities in the adult plant field evaluation, may be new sources of resistance to P. pachyrhizi.

Photorefractive keratectomy for moderate myopia with the VISX and Summit excrimer lasers: a retrospective study

Objetivo: Apresentar os resultados obtidos com ceratectomia fotorrefrativa (PRK) para a correção de miopia variando de -4,0 a -6,0 dioptrias realizadas com os excimer lasers VISX e Summit. Métodos: Para o estudo foram avaliados os resultados de PRK realizados em pacientes com idade entre 20 e 45 anos, miopia entre -4,0 e -6,0 diotropias e astigmatismo até 1,0 diotropia .O grupo operado com o laser da marca Summit era composto de 51 olhos. O equivalente esférico médio pré-operatório era de -5,22ñ0,17 diatropias e as cirurgias foram realizadas com o Excimed UV 200 LA Excimer Laser. O grupo operado com o laser VISX, era composto de 53 olhos e o erro refrativo preoperatório era de -4,85ñ0,16 diatropias e as cirurgias foram realizadas com o Twenty/Twenty Excimer Laser.

Mean arterial blood pressure changes in premature infants and those at risk for intraventricular hemorrhage.

Bedside microcomputer-derived, minute-to-minute mean arterial pressure (MAP) values during the first 48 hours of life were studied in 100 preterm babies with birth weight less than or equal to 1500 gm. In those babies (n = 72) with no periventricular-intraventricular hemorrhage (PV-IVH) or with grade 1 PV-IVH, the MAP values increased during the study period, with minute-to-minute variation and interval undulation. The MAP values in those with birth weight greater than 1000 gm were higher than in those of lower birth weight. Infants in whom grades 2 to 4 PV-IVH developed (n = 28) had consistently lower MAP values during the study period. Minute-to-minute variability, expressed as the average of the coefficients of variation at 15-minute intervals, did not differ between birth weight groups, nor did they differ between the PV-IVH group and their matched control subjects. However, those with PV-IVH spent a greater percentage of time, with a coefficient of variation greater than or equal to 13% or less than 3%, than their matched control subjects spent (p less than 0.005). This study provides reference data for MAP changes in premature babies. The observed MAP changes in those with PV-IVH lend support to a significant role for MAP alterations in the pathogenesis of PV-IVH.

Range-gated pulsed Doppler ultrasonographic evaluation of carotid arterial blood flow in small preterm infants with patent ductus arteriosus.

Range-gated pulsed Doppler (RGPD) ultrasonography was utilized to study the effect of a patent ductus arteriosus (PDA) on carotid arterial blood flow in small preterm infants. Carotid arterial flow velocity studies were performed on 23 preterm infants, sampling right and left carotid arteries. Studies on seven infants after PDA ligation and on seven who developed no evidence of PDA were used as controls. A strong relationship was demonstrated between diastolic reversal in the carotid arteries and PDA. The results of this study indicate that the RGPD flow velocity curve from the carotid artery is more sensitive than M-mode echocardiography or clinical examination in detecting PDA, and that PDA in small preterm infants is associated with a distinct abnormality in the carotid arterial flow pattern.