Stability of cucurbitacin E in human plasma: chemical hydrolysis and role of plasma esterases

It was shown previously that the anticancerous cytotoxic oxygenated triterpenes, cucurbitacin E (Cuc E) and its deacetylated form, cucurbitacin I (Cuc I), interacted differently with human serum albumin. In this study, the biochemical stability of Cuc E was investigated in vitro by reverse‐phase high performance liquid chromatography. The hydrolysis rate in acidic and alkaline solutions, and in enzymatic conditions in human plasma and in purified plasma esterase solutions of butyrylcholinesterase and albumin, was compared with that measured in phosphate buffer saline (pH 7.4). Cuc E hydrolysis was detected in all the in vitro tests, but the extent of hydrolysis varied according to the different enzymatic and non‐enzymatic conditions. A remarkable rapid hydrolysis of Cuc E was detected in acidic and alkaline solutions. A significant rate of hydrolysis of Cuc E was monitored in human plasma and was associated with the detection of Cuc I. The stability of Cuc E was greatly enhanced in the presence of albumin. However, purified butyrylcholinesterase had no effect on Cuc E stability. Among specific inhibitors of plasma esterases, only EDTA increased Cuc E stability, suggesting that paraoxonase is the human plasma esterase involved in the hydrolysis of Cuc E. Copyright © 2009 John Wiley & Sons, Ltd.     

Comparison of the pretranslational regulation of FSH synthesis by gonadal steroids in rats and mice

There are significant differences between rats and mice in the gonadal regulation of several aspects of gonadotroph function. To investigate whether these extend to the pretranslational regulation of FSH synthesis by gonadal steroids, we have measured FSH-beta mRNA levels following gonadectomy and sex-steroid replacement and have related these to serum and pituitary FSH as a reflection of overall hormone synthesis. In ovariectomized rats, FSH-beta mRNA levels increased by 8 h, decreased, and then rose progressively over the next 28 days. A similar pattern of response was observed in orchidectomized rats. In mice, there were progressive increases in FSH-beta mRNA levels in both males and females following gonadectomy, without evidence of the early peaks observed in rats. In both species, the change in FSH-beta mRNA levels after gonadectomy was greater in females than in males. These changes in FSH-beta mRNA following gonadectomy were paralleled by changes in the serum FSH concentration. In ovariectomized female rats and mice, pituitary FSH stores increased by 8 h and 3 days respectively, whereas in male rats, pituitary FSH content did not rise until 10 days after orchidectomy. The most striking species difference was the marked and prolonged reduction of pituitary FSH after orchidectomy of mice. Treatment of rats and mice from the time of ovariectomy, with a dose of oestradiol that prevents increases in serum LH, only partially attenuated the rises in FSH-beta mRNA and serum FSH and did not prevent the increase in pituitary FSH content. Treatment of intact or orchidectomized rats with testosterone suppressed FSH-beta mRNA levels to 50% below intact control values without affecting pituitary FSH content.(ABSTRACT TRUNCATED AT 250 WORDS)     

Causalgia: a wartime experience--report of twenty treated cases

During the 10-year period from 1975 to 1985 20 patients suffering from causalgia were treated. There were 15 men and five women. Ages ranged from 17 to 45 years (mean, 23). All were war casualties injured by high-velocity missiles. The median nerve was involved in eight cases, ulnar nerve in six, brachial plexus in four, sciatic nerve in four, radial nerve in three, and there were multiple nerve injuries in five cases. The diagnosis of causalgia was based on the characteristic clinical picture and was confirmed by sympathetic blocks. All patients were treated by sympathectomy and all had complete dramatic relief in the immediate postoperative period. Followup ranged from 4 months to 10 years (mean, 5.3 yr).     

Alginate-Based Hydrogels and Tubes,as Biological Macromolecule-Based Platforms for Peripheral Nerve Tissue Engineering: A Review

Annals of Biomedical Engineering - Unlike the central nervous system, the peripheral nervous system (PNS) has an inherent capacity to regenerate following injury. However, in the case of large...     

Prognosis value of partial arterial oxygen pressure in patients with septic shock subjected to pre-hospital invasive ventilation

Objective

Mechanical ventilation can help improve the prognosis of septic shock. While adequate delivery of oxygen to the tissue is crucial, hyperoxemia may be deleterious. Invasive out-of-hospital ventilation is often promptly performed in life-threatening emergencies. We propose to determine whether the arterial oxygen pressure (PaO₂) at the intensive care unit (ICU) admission is associated with mortality in patients with septic shock subjected to pre-hospital mechanical ventilation.

Fibrilación auricular en pacientes con COVID-19. Utilidad de la puntuación CHA2DS2-VASc: un análisis del registro internacional HOPE COVID-19

Introduction and objectivesCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Atrial fibrillation (AF) is common in acute situations, where it is associated with more complications and higher mortality.MethodsAnalysis of the international HOPE registry (NCT04334291). The objective was to assess the prognostic information of AF in COVID-19 patients. A multivariate analysis and propensity score matching were performed to assess the relationship between AF and mortality. We also evaluated the impact on mortality and embolic events of the CHA₂DS₂-VASc score in these patients.ResultsAmong 6217 patients enrolled in the HOPE registry, 250 had AF (4.5%). AF patients had a higher prevalence of cardiovascular risk factors and comorbidities. After propensity score matching, these differences were attenuated. Despite this, patients with AF had a higher incidence of in-hospital complications such as heart failure (19.3% vs 11.6%, P = .021) and respiratory insufficiency (75.9% vs 62.3%, P = .002), as well as a higher 60-day mortality rate (43.4% vs 30.9%, P = .005). On multivariate analysis, AF was independently associated with higher 60-day mortality (hazard ratio, 1.234; 95%CI, 1.003-1.519). CHA₂DS₂-VASc score acceptably predicts 60-day mortality in COVID-19 patients (area ROC, 0.748; 95%CI, 0.733-0.764), but not its embolic risk (area ROC, 0.411; 95%CI, 0.147-0.675).ConclusionsAF in COVID-19 patients is associated with a higher number of complications and 60-day mortality. The CHA₂DS₂-VASc score may be a good risk marker in COVID patients but does not predict their embolic risk.     

In vivo analysis of the cell cycle dependent association of the bovine papillomavirus E2 protein and ChlR1

Clathrin-mediated endocytosis was previously implicated as one of the cellular pathways involved in filoviral glycoprotein mediated viral entry into target cells. Here we have further dissected the requirements for different components of this pathway in Ebola versus Marburg virus glycoprotein (GP) mediated viral infection. Although a number of these components were involved in both cases; Ebola GP-dependent viral entry specifically required the cargo recognition proteins Eps15 and DAB2 as well as the clathrin adaptor protein AP-2. In contrast, Marburg GP-mediated infection was independent of these three proteins and instead required beta-arrestin 1 (ARRB1). These findings have revealed an unexpected difference between the clathrin pathway requirements for Ebola GP versus Marburg GP pseudovirion infection. Anthrax toxin also uses a clathrin-, and ARRB1-dependent pathway for cellular entry, indicating that the mechanism used by Marburg GP pseudovirions may be more generally important for pathogen entry.     

Unusual case of closed rupture of both extensor tendons of the index finger

Extensor tendon rupture is a common condition following penetrating injuries, whereas closed rupture is rare unless in a mallet finger. We describe an unusual case of closed rupture of both extensor tendons to the index finger. The extensor indicis proprius and extensor digitorum longus were avulsed proximal to the extensor retinaculum in a 23-year-old male patient due to forced hyperflexion of his index finger. Investigation was done in the Department of Orthopaedic Surgery at the Notre Dame Des Secours University Hospital, Byblos Lebanon.     

Genetic analysis of fenhexamid-resistant field isolates of the phytopathogenic fungus Botrytis cinerea

The hydroxyanilide fenhexamid, one of the latest antibotrytis fungicides, active especially against leotiomycete plant-pathogenic fungi, inhibits 3-ketoreductase of the C-4-demethylation enzyme complex during ergosterol biosynthesis. We isolated Botrytis cinerea strains resistant to various levels of fenhexamid from French and German vineyards. The sequence of the gene encoding 3-ketoreductase, erg27, varied according to levels of resistance. Highly resistant isolates, termed HydR3(+), all presented a modification of the phenylalanine at the C terminus of the putative transmembrane domain at position 412, either to serine (85% of the isolates), to isoleucine (11.5% of the isolates), or to valine (3.5% of the isolates). The introduction of the erg27(HydR3(+)) allele into a fenhexamid-sensitive strain by means of a replicative plasmid conferred fenhexamid resistance on the resulting transformants, showing that the mutations at position 412 are responsible for fenhexamid resistance. Weakly to moderately resistant isolates, termed HydR3(-), showed different point mutations between the strains in the sequenced regions of the erg27 gene, corresponding to amino acid changes between positions 195 and 400 of the protein. The erg27(HydR3(-)) alleles on the replicative vector introduced into a sensitive strain did not confer resistance to fenhexamid. Genetic crosses between HydR3(-) and sensitive strains showed strict correlation between the sequenced mutation in the erg27 gene and the resistance phenotypes, suggesting that these mutations are linked to fenhexamid resistance. The HydR3 mutations possibly modify the affinity of the 3-ketoreductase enzyme for its specific inhibitor, fenhexamid.