Base-catalysed rearrangements of 5-oxodihydroisoxazoles

Five distinct pathways for the reaction of isoxazol-5(2H)-ones with bases or nucleophiles have been reported, and are detailed herein. That investigated in greatest detail, and of greatest application in heterocyclic synthesis, is that of isoxazolones unsubstituted at C-3, in which the sequentially formed ketenimine, alpha-lactone and ketene may all react with a nucleophile.

Er(3+) doped phosphoniobate glasses and planar waveguides: structural and optical properties

Phosphoniobate glasses with composition (mol%) (100-x) NaPO(3)-xNb(2)O(5) ( x varying from 11 to 33) were prepared and characterized by means of thermal analysis, Fourier transform infrared spectroscopy, Raman scattering and (31)P nuclear magnetic resonance. The addition of Nb(2)O(5) to the polyphosphate base glass leads to depolymerization of the metaphosphate structure. Different colors were observed and assigned as indicating the presence of Nb(4+) ions, as confirmed by electron paramagnetic resonance measurements. The color was observed to depend on the glass composition and melting temperature as well. Er(3+) containing samples were also prepared. Strong emission in the 1550 nm region was observed. The Er(3+4)I(15/2) emission quantum efficiency was observed to be 90% and the quenching concentration was observed to be 1.1 mol%( 1.45 x 10(20) ions cm(-3)). Planar waveguides were prepared by Na(+)-K(+)-Ag(+) ion exchange with Er(3+) containing samples. Optical parameters of the waveguides were measured at 632.8, 543.5 and 1550 nm by the prism coupling technique as a function of the ion exchange time and Ag(+) concentration. The optimized planar waveguides show a diffusion depth of 5.9 mu m and one propagating mode at 1550 nm.

The crystal structure of free human hypoxanthineguanine phosphoribosyltransferase reveals extensive conformational plasticity throughout the catalytic cycle

Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the synthesis of the purine nucleoside monophosphates, IMP and GMP, by the addition of a 6-oxopurine base, either hypoxanthine or guanine, to the 1-beta-position of 5-phospho-U-D-ribosyl-1-pyrophosphate (PRib-PP). The mechanism is sequential, with PRib-PP binding to the free enzyme prior to the base. After the covalent reaction, pyrophosphate is released followed by the nucleoside monophosphate. A number of snapshots of the structure of this enzyme along the reaction pathway have been captured. These include the structure in the presence of the inactive purine base analogue, 7-hydroxy [4,3-d] pyrazolo pyrimidine (HPP) and PRib-PP. Mg2+, and in complex with IMP or GMP. The third structure is that of the immucillinHP.Mg2+.PPi complex, a transition-state analogue. Here, the first crystal structure of free human HGPRT is reported to 1.9 angstrom resolution, showing that significant conformational changes have to occur for the substrate(s) to bind and for catalysis to proceed. Included in these changes are relative movement of subunits within the tetramer, rotation and extension of an active-site alpha-helix (D137-D153), reorientation of key active-site residues K68, D137 and K165, and the rearrangement of three active-site loops (100-128, 165-173 and 186-196). Toxoplasina gondii HGXPRT is the only other 6-oxopurine phosphoribosyltransferase structure solved in the absence of ligands. Comparison of this structure with human HGPRT reveals significant differences in the two active sites, including the structure of the flexible loop containing K68 (human) or K79 (T gondii). (c) 2005 Elsevier Ltd. All rights reserved.

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.

The systematics and biology of the south African gall-inducing scale insect, Calycicoccus merwei brain (Hemiptera : Coccoidea : Eriococcidae)

The scale insect genus Calycicoccus Brain has a single described species, C. merwei Brain, which is endemic to southeastern South Africa. Females of C. merwei induce small, mostly conical galls on the foliage of their host tree, Apodytes dimidiata E. Meyer ex Arn. (Icacinaceae), which has a wider, mostly coastal distribution, than that currently known for the scale insect. Calycicoccus has been placed in the family Eriococcidae and may be related to the South American genus Aculeococcus Lepage. No other native eriococcid species have been described so far in South Africa, although the family is diverse in other Gondwanan regions. This paper summarizes the biology of C. merwei, redescribes the adult female, describes the adult male, the second-instar female and the first-instar nymphs for the first time, and reconsiders the phylogenetic relationships of the genus. The adult female is shown to have unusual abdominal segmentation, in that segment I is present both dorsally and ventrally, but a segment is absent ventrally on the middle abdomen. First-instar nymphs are sexually dimorphic; males have a larger and relatively narrower body, larger mouthparts, longer antennae and legs, and more thoracic dorsal setae compared with females. Molecular data from nuclear small-subunit ribosomal DNA (18S) and elongation factor 1 alpha (EF-1a) show C. merwei to have no close relatives among the Eriococcidae sampled to date. Instead, the Calycicoccus lineage is part of a polytomy near the base of the Eriococcidae. Molecular dating of the node suggests that the Calycicoccus lineage diverged from other eriococcids more than 100 Mya. These data support the placement of Calycicoccus as the only genus in the subfamily Calycicoccinae Brain.

Potassium in Hemorrhagic Shock: A Potential Marker of Tissue Hypoxia

Background: This study was designed to evaluate serum potassium level variation in a porcine model of hemorrhagic shock ( HS). Methods: Eight pigs were studied in a controlled hemorrhage model of HS. Blood withdrawal began at a 50 mL/min to 70 mL/min rate, adjusted to reach a mean arterial pressure ( MAP) level of 60 mm Hg in 10 minutes. When MAP reached 60 mm Hg, the blood withdrawal rate was adjusted to maintain a MAP decrease rate of 10 mm Hg every 2 minutes to 4 minutes. Arterial and mixed venous blood samples were collected at MAP levels of 60 mm Hg, 50 mm Hg, 40 mm Hg, 30 mm Hg, 20 mm Hg, and 10 mm Hg and analyzed for oxygen saturation, PO(2), PCO(2), potassium, lactate, bicarbonate, hemoglobin, pH, and standard base excess. Results: Significant increase in serum potassium occurred early in all animals. The rate of rise in serum potassium and its levels accompanied the hemodynamic deterioration. Hyperkalemia ( K >5 mmol/L) incidence was 12.5% at 60 mm Hg and 50 mm Hg, 62.5% at 40 mm Hg, 87.5% at 30 mm Hg, and 100% at 20 mm Hg. Strong correlations were found between potassium levels and lactate ( R = 0.82), SvO(2) ( R = 0.87), Delta pH ( R = 0.83), and Delta PCO(2) ( R = 0.82). Conclusions: Serum potassium increase accompanies the onset of HS. The rise in serum potassium was directly related to the hemodynamic deterioration of HS and strongly correlated with markers of tissue hypoxia.

Perineural Invasion in Aggressive Skin Carcinomas of the Head and Neck

Introduction: Perineural invasion is a well-recognized form of cancer dissemination. However, it has been reported only in few papers concerning cutaneous carcinomas ( basal cell, BCC, and squamous cell, SCC). Moreover, the incidence is considered to be very low. Niazi and Lambert [Br J Plast Surg 1993; 46: 156-157] reported only 0.18% of perineural invasion among 3,355 BCCs. It is associated with high-risk subtypes, as morphea-like, as well as with an increased risk of local recurrence. No paper was found in the literature looking for perineural invasion in very aggressive skin cancers with skull base extension, with immunohistochemical analysis. Methods: This is a retrospective review, including 35 very advanced skin carcinomas with skull base invasion (24 BCCs and 11 SCCs, operated on at a single institution from 1982 to 2000). Representative slides were immunohistochemically evaluated with antiprotein S-100, in order to enhance nerve fibers and to detect perineural invasion. The results were compared to 34 controls with tumors with a good outcome, treated in the same time frame at the same Institution. Results: Twelve (50.0%) of the BCCs with skull base invasion had proven perineural invasion, as opposed to only 1 (4.6%) of the controls, and this difference was statistically significant (p < 0.001). Regarding SCCs, 7 aggressive tumors (63.6%) showed perineural invasion compared to only 1 (10.0%) of the controls, but this difference did not reach significance (p=0.08), due to the small number of cases. Conclusions: In this series, it was demonstrated that immunohistochemically detected perineural invasion was very prevalent in advanced skin carcinomas. In addition, it was statistically associated with extremely aggressive BCCs with skull base invasion. Copyright (c) 2008 S. Karger AG, Basel

Skull Base Cephalometric Changes in Cranial Expansion by Springs

Background: The use of springs in cranial expansion has demonstrated to be effective for craniosynostosis treatment. The spring-exerted expansile action has been observed when springs are placed both in the sagittal and parasagittal regions, mainly in scaphocephaly. In this study, a variation in cephalometric measurements under expansible spring action on the skull base was analyzed. Methods: Thirteen 4-week-old New Zealand white rabbits were divided into 4 groups: group 1, in which only amalgam markers were used (control); group 2, in which amalgam markers were used, and a sagittal suturectomy was performed; group 3, in which amalgam markers were used, and a sagittal suturectomy was performed with placement of expansible springs in the interparietal region; and group 4, in which markers were used, and a linear parasagittal craniectomy was performed with spring placement. All animals were killed at weeks 2, 4, 8, and 12. Radiologic control with cephalometric study was performed. Results: Distraction of amalgam markers in the groups with springs was greater than in those without springs. A proportional change in the angles measured through craniometry was observed in these groups. Conclusions: The experimental rabbit model was shown to be adequate to the analysis proposed by the study. Under the action of springs, the groups with sagittal and parasagittal osteotomy were found to present a similar distraction of amalgam markers. A concomitant change in cephalometric measurements occurred, suggesting a change in the skull base mediated by expansible springs placed both in the sutural and nonsutural sites.

Race modeling: An effective cognitive strategy for the 100 m sprinter?

The purpose of this study was to investigate the effects of a specific cognitive race plan on 100 m sprint performance, Twelve elite sprinters (11 male and 1 female) performed 100 m time trials under normal (control) conditions and then under experimental conditions (use of race cues). In the experimental condition, participants were asked to think about specific thought content in each of three segments of the 100 m. A multiple baseline design was employed. A mean improvement of 0.26 s was found. Eleven of the 12 participants showed improvement using the specific cognitive race plan (p < .005). Participants also produced more consistent sprint performances when using the cues (p < .01). Subjective evaluations made by the participants unanimously supported the use of the race plan for optimizing sprint performance. Environmental conditions, effort, and practice effects were considered as possible influences on the results.

Chemical characterization of soils of a tropical humid forest zone: A methodology

A methodology, based on a combination of routinely performed analyses and investigation of fundamental charge and anion sorption properties, was used to characterize the soils of the humid forest zone of Cameroon, In general, the soils have about 2 cmol kg(-1) permanent negative charge, with about 1 cmol kg(-1) from variable-charge sources at current soil pH values, Furthermore, they are impoverished with respect to Ca, Mg, and K, while Al frequently dominates the exchange complex. Thus, the ability of these soils to retain base cations is more limited than is suggested by the cation-exchange capacity (CEC), Therefore we propose the concept of a degradation index (DI) defined as: DI = 100(CEC5.5 - sum of basic cations)/CEC5.5, where CEC5.5 is the CEC measured at pH 5.5, This index encompasses degradation a soil may have experienced from natural or man-made causes, Extractable PO4 concentrations are considered very low and the soils have a moderate to high capacity to fix added PO4. Surface soil SO4 concentrations are considered marginal to deficient for plant growth, though adequate reserves of SO4 are held in the subsoil by SO4 sorption, The approach used demonstrated that the five morphologically different soil profile classes identified in the zone have similar chemical characteristics. Thus, the results of experimentation conducted on one of the soil profile classes will be applicable throughout the zone, Furthermore, the approach has provided a means of identifying comparable soil types in other parts of the world and will guide technology transfer, The analytical methods used in this study are relatively simple and require no specialized equipment, and are therefore within the capabilities of many laboratories in the developing world.

ARTHROSCOPIC TREATMENT OF ACUTE ACROMIOCLAVICULAR JOINT DISLOCATION USING SUTURE ANCHORS

Objective: To present the clinical and radiographic results of a case series of patients with acute acromioclavicular dislocation (MD) treated by arthroscopic coracoclavicular fixation with suture anchors. Method: Twenty patients with AAD with less than 30 days since the injury were submitted to a coracoclavicular stabilization procedure using 2 suture anchors placed at the base of the coracoid process. Each suture anchor was connected to 2 strands of No.2 nonabsorbable-braided sutures, which were passed through the holes drilled in the clavicle and tied to the upper surface of the clavicle. The coracoclavicular distance was measured and compared to the opposite side using radiographic evaluation. Constant and UCLA scores were used to determine clinical and functional evaluation after 6 months. Results: Of the initial twenty cases, six were submitted to a new surgical procedure and were excluded from the study. Of the fourteen patients remaining, only two maintained the initial reduction, while the remainder presented some degree of reduction loss. The Constant and UCLA score averages were 94.79 (82-100) and 32.64 (26-35) respectively. Conclusion: The technique had a high incidence of reduction loss after 6 months of follow up. The clinical and functional evaluation was satisfactory, with a high average score. Level of Evidence: Level III, retrospective study.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.