The substitution reactions of VCp2(CO) with some selected olefins have been studied. Tetracyanoethylene (tcne) and fumaronitrile (fn), containing electron-withdrawing substituents, promptly react ...with VCp2(CO) with quantitative formation of VCp2(tcne) and VCp2(fn), respectively, while acrylonitrile and diethyl fumarate (defu) gave partial displacement of coordinated carbon monoxide under a CO atmosphere. No CO displacement from VCp2(CO) was observed with cyclooctene and norbornene. The carbonylation of VCp2(defu) (VCp2(defu) + CO ⇄ VCp2(CO) + defu) has been studied gas volumetrically from both sides, and the equilibrium constant for the displacement of coordinated defu by carbon monoxide was estimated to be 55 ± 8 at 298.5 K. Variable-temperature experiments between 298.5 and 327.7 K have shown the enthalpy change to be −2.4 kcal mol-1. The equilibrium constant for the addition of defu to VCp2 (VCp2 + defu ⇄ Cp2(defu)) has been evaluated spectroscopically to be 150 ± 11 at 298.5 K. From the available data, the equilibrium constant for the addition of carbon monoxide to VCp2 (VCp2 + CO ⇄ VCp2(CO)) has been calculated to be K a = (8.2 ± 0.4) × 103: i.e., about 2 orders of magnitude higher than that for the complexation of defu. The present data for the 3d3 system of vanadium(II) (ν̃CO in toluene 1881 cm-1) are compared with those exhibited by the 5d10 system of AuCl(CO) (ν̃CO in toluene 2153 cm-1), whose behavior consistently shows an opposite dependence, as far as the olefin/CO competition is concerned, on the nature of the olefin.
Category:
Basic Sciences/Biologics
Introduction/Purpose:
A scientifically sound validated foot and ankle specific outcome measure for different European languages is still missing. Indeed, ...language-specific cross cultural validation in other languages than English is largely absent. Some outcome measures were validated for specific pathologies such as hallux valgus, ankle arthritis or flatfoot. The European Foot and Ankle Society (EFAS) established in 2013 a Score Committee to develop, validate, and publish a new score, the “EFAS Score”, which is not specific for single pathologies for different European languages. The principal aim of this project was to develop and validate the EFAS Score simultaneously for different European languages.
Methods:
The EFAS Score was developed and validated in three stages: 1) item (question) identification, 2) item reduction and scale exploration, 3) confirmatory analyses and responsiveness. The following score specifications were chosen: scale/subscale (Likert 0-4), questionnaire based, outcome measure, patient related outcome measurement. For stage 3, data were collected pre- operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using analyses from classical test theory and item response theory.
Results:
Stage 1 resulted in 31 general and 7 sports related questions. In Stage 2, a 6-item general EFAS Score was constructed using English, German, French and Swedish language data. In Stage 3, internal consistency of the scale was confirmed in seven languages: the original four languages, plus Dutch, Italian and Polish (Cronbach’s Alpha >0.86 in all language versions).
Responsiveness was good, with moderate to large effect sizes in all languages, and significant positive association between the EFAS Score and patient-reported improvement.
No sound EFAS Sports Score could be constructed.
Conclusion:
The multi-language EFAS Score has been successfully validated for orthopaedic foot and ankle surgery populations incorporating a wide variety of foot and ankle pathologies, including language-specific validation in seven languages so far (English, German, French, Swedish, Dutch, Italian, Polish). Validation for other languages (Danish, Finnish, Norwegian, Portuguese, Spanish, Turkish) is in progress. All validated score versions are freely available at www.efas.co.
Objective: The purpose of this study was to evaluate the renoprotective effects of fenoldopam in patients at high risk of postoperative acute kidney injury undergoing elective cardiac surgery ...requiring cardiopulmonary bypass. Design: A double-blind randomized clinical trial. Setting: Hospital. Participants: One hundred ninety-three patients. Interventions: Patients undergoing cardiac surgery were randomly assigned to receive a continuous infusion of fenoldopam, 0.1 μg/kg/min (95 patients), or placebo (98 patients) for 24 hours. Patients were included if at least 1 of the following risk factors was present: preoperative serum creatinine ≥1.5 mg/dL, age >70 years, diabetes mellitus, or prior cardiac surgery. Serum creatinine and urinary output were measured at baseline (T1), 24 hours (T2), and 48 hours after surgery (T3). Acute kidney injury was defined as a postoperative serum creatinine level of ≥2 mg/dL with an increase in serum creatinine level of 0.7 mg/dL or greater from preoperative to maximum postoperative values. Measurements and Main Results: Acute kidney injury developed in 12 of 95 (12.6%) patients receiving fenoldopam and in 27 of 98 (27.6%) patients receiving placebo ( p = 0.02), whereas renal replacement therapy was started in 0 of 95 and 8 of 98 (8.2%) patients, respectively ( p = 0.004). Serum creatinine was similar at baseline (1.8 ± 0.4 mg/dL v 1.9 ± 0.3 mg/dL) in the fenoldopam and placebo groups but differed significantly ( p < 0.001 and p < 0.001) 24 hours (1.6 ± 0.2 mg/dL v 2.5 ± 0.6 mg/dL) and 48 hours (1.5 ± 0.3 mg/dL v 2.8 ± 0.4 mg/dL) after the operation. Conclusions: A 24-hour infusion of 0.1 μg/kg/min of fenoldopam prevented acute kidney injury in a high-risk population undergoing cardiac surgery.
A girl carrying a de novo balanced 13-14 robertsonian translocation showed a clinical phenotype with severe hypotonia, hyperextensible joints, frontal bossing, asymmetric face, no mental retardation, ...severe scoliosis and motor delay. In situ hybridization analysis on chromosome spreads revealed the presence of the two centromeres in the rearranged chromosomes. Molecular analysis on genomic DNA showed the presence in the proposita of two chromosomes 14 of maternal origin and no chromosome 14 from the father indicating a maternal monocentric uniparental disomy for chromosome 14 (mUPD14). Our patient shows several similarities with other reported cases of mUPD14, suggesting imprinting of a region(s) of chromosome 14 and defining a possible mUPD14 Syndrome.
Idrapril is the prototype of a new chemical class of angiotensin converting enzyme (ACE) inhibitors, the hydroxamic non-amino acid derivatives. Idrapril strongly inhibited rat and human plasma ACE ...and rabbit lung ACE (IC507–12 nM) as well as the pressor response induced by angiotensin I in anesthetized rats (ED5063 nmol/kg i.v.). Idrapril (0.04–23 μmol/kg i.v.) lowered the blood pressure dose dependently, up to 20–35%, in different models of hypertension (sodium-depleted spontaneously hypertensive rat, two-kidney-one-clip renal hypertensive rat, and aortic-coarctated rat), its profile being similar to that of captopril in terms of potency and efficacy. Idrapril and captopril reduced the blood pressure and potentiated substance P-induced bronchoconstriction in the guinea pig to the same extent, suggesting a similar degree of ACE inhibition in the circulation. However, idrapril potentiated capsaicin-induced bronchoconstriction (a model that has been related to the liability of ACE inhibitors to produce cough in patients) less effectively than captopril. We conclude that effective ACE inhibition in vitro and in vivo can be obtained with this novel class of compounds.
Abstract A new design for a 3-part ankle replacement was developed in an effort to achieve compatibility with the naturally occurring ligaments of the ankle by allowing certain fibers to remain ...isometric during passive motion. In order to test the design concept clinically, 158 prostheses were implanted in 156 patients within a 9-center trial and were followed up for a mean of 17 (range 6 to 48) months. The mean age at the time of surgery was 60.5 (range 29.7 to 82.5) years. Outcome measures included the American Orthopaedic Foot & Ankle Surgery hindfoot-ankle score and range of motion measured on lateral radiographs of the ankle. The preoperative American Orthopaedic Foot & Ankle Surgery score of 36.3 rose to 74.6, 78.6, 76.4, and 79.0, respectively, at 12, 24, 36, and 48 months. A significant correlation between meniscal bearing movement on the tibial component (mean 3.3 mm; range 2 to 11 mm) and range of flexion at the replaced ankle (mean 26.5°; range 14° to 53°) was observed in radiograms at extreme flexions. Two (1.3%) revisions in the second and third postoperative years necessitated component removal (neither were for implant failure), and 7 (4.4%) further secondary operations were required. The results of this investigation demonstrated that non-anatomic–shaped talar and tibial components, with a fully conforming interposed meniscal bearing, can provide safety and efficacy in the short term, although a longer follow-up period is required to more thoroughly evaluate this ankle implant.
Bradykinin (BK) is a vasoactive peptide reputed to play an important role in cardiovascular homeostasis. In this study, we describe the cardiovascular changes (mean blood pressure (BP) and heart rate ...(HR)) induced by the i.v. administration (left jugular vein) of two selective kinin B2 receptor antagonist, namely icatibant (0.1-1 micromol/kg as a bolus) and MEN1 1270 (0.1-1 micromol/kg as a bolus or 1 micromol/kg infused in 15 or 60 min), in urethane-anaesthetized or conscious rats with an indwelling catheter implanted in the right carotid artery for BP measurements. In conscious rats, icatibant at 0.1 or 0.3 micromol/kg did not change BP but at 0.1 micromol/kg increased HR at 30 min from administration. MEN1 1270 at 0.1 or 0.3 micromol/kg induced a dose-related increase in BP and a concomitant bradycardia (significant at 0.3 micromol/kg) lasting for 5 or 30 min, respectively. Icatibant at 1 micromol/kg induced a slight (P < 0.05) increase in BP that resolved in 5 min and a biphasic tachycardia (peaks at 30 and 90 min from administration). MEN1 1270 at 1 micromol/kg induced a triphasic change in HR (tachycardia in the first 5 min, bradycardia at 30 min, and tachycardia at 90 and 120 min) and a biphasic change in BP (hypotension at 15 min and hypertension at 30 min). The i.v. infusion of MEN1 1270 (1 micromol/kg in 15 or 60 min) produced hypertension, whereas HR was increased only following the 15-min infusion. In urethane-anaesthetized rats, both icatibant and MEN1 1270 (0.1 micromol/kg as a bolus) increased BP and the onset for this effect was correlated with the time course of the antagonism of BK-induced hypotension, where the effect of MEN1 1270 was more rapid than that of icatibant. These results indicate that kinin B2 receptor antagonists can induce acute cardiovascular effects, and the reason for the different haemodynamic profile between icatibant and MEN1 1270 could be putatively attributed to kinetic characteristics.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The pharmacokinetics of MEN 11420 nepadutant, c(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leuc(2beta-5beta++ +), a potent glycosylated analogue of the selective, bicyclic peptide, tachykinin NK2 receptor ...antagonist MEN 10627 c(Met-Asp-Trp-Phe-Dpr-Leu)c(2beta-5beta), were studied in rats after different routes of administration. The plasma concentration profile for MEN 11420 after iv administration (1 mg/kg) was compared with that for the parent compound MEN 10627. The mean plasma half-life (44 min) and AUC value (285 micrograms.min/ml) for MEN 11420 were almost 3-fold greater than those for MEN 10627, and the systemic clearance was reduced to one third. The absolute bioavailability of MEN 11420 after intranasal (1 mg/kg) or ip (1 mg/kg) administration was virtually complete. However, bioavailability was only approximately 5% after intrarectal treatment (5 mg/kg) and was too low to be quantified (<3%) after sublingual (1 mg/kg) or oral (10 mg/kg) doses. The urinary excretion of unchanged compound, after an iv dose of 1 mg/kg, was approximately 34% of the dose for MEN 11420 but was <2% for MEN 10627. This is in agreement with in vitro data showing that MEN 11420 is more resistant to hydrolytic and oxidative metabolism than is MEN 10627. It is concluded that the hydrophilic modification of MEN 10627 to produce MEN 11420 resulted in marked improvement in the pharmacokinetic and metabolic characteristics of the peptide.
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