The first multicentre study on coronary anomalies in the Netherlands: MuSCAT

BackgroundCurrent guidelines on coronary anomalies are primarily based on expert consensus and a limited number of trials. A gold standard for diagnosis and a consensus on the treatment strategy in this patient group are lacking, especially for patients with an anomalous origin of a coronary artery from the opposite sinus of Valsalva (ACAOS) with an interarterial course.AimTo provide evidence-substantiated recommendations for diagnostic work-up, treatment and follow-up of patients with anomalous coronary arteries.MethodsA clinical care pathway for patients with ACAOS was established by six Dutch centres. Prospectively included patients undergo work-up according to protocol using computed tomography (CT) angiography, ischaemia detection, echocardiography and coronary angiography with intracoronary measurements to assess anatomical and physiological characteristics of the ACAOS. Surgical and functional follow-up results are evaluated by CT angiography, ischaemia detection and a quality-of-life questionnaire. Patient inclusion for the first multicentre study on coronary anomalies in the Netherlands started in 2020 and will continue for at least 3 years with a minimum of 2 years of follow-up. For patients with a right or left coronary artery originating from the pulmonary artery and coronary arteriovenous fistulas a registry is maintained.ResultsPrimary outcomes are: (cardiac) death, myocardial ischaemia attributable to the ACAOS, re-intervention after surgery and intervention after initially conservative treatment. The influence of work-up examinations on treatment choice is also evaluated.ConclusionsStructural evidence for the appropriate management of patients with coronary anomalies, especially (interarterial) ACAOS, is lacking. By means of a structured care pathway in a multicentre setting, we aim to provide an evidence-based strategy for the diagnostic evaluation and treatment of this patient group.Supplementary InformationThe online version of this article (10.1007/s12471-021-01556-9) contains supplementary material, which is available to authorized users.     

Transformation of C19-steroids and testosterone production by sterol-transforming strains of Mycobacterium spp.

Redox conversions of exogenic C₁₉-steroids (androstenedione (AD), androstadienedione (ADD), testosterone and 1(2)-dehydrotestosterone) were studied using a mutant strain of Mycobacterium sp. Et1 with high level of 17β-hydroxysteroid dehydrogenase (17-HSD) activity. Factors affecting target 17β-reduction and side reactions by resting and growing cells were estimated. The effects of glucose supplementation, pH, mode of substrate addition were identified. The results confirmed that double reduction of androstadienedione, both of 17-keto group and 1(2)-double bond, is more effective for testosterone formation than a single reduction of 17-keto group of AD. These findings argued for the application of the strain capable of sterol side chain degradation and expressed 17-HSD, 3-ketosteroid-1(2)-dehydrogenase and 1-ene-reductase activities, for testosterone obtaining from sitosterol. Under optimal conditions, the conversion of sitosterol (5 g/l) by Mycobacterium sp. VKM Ac-1816D in laboratory fermenter resulted in 50–55% molar yield of testosterone.     

Regulation of oxidative activity and delta psi of liver mitochondria of active and hibernating gophers. The role of phospholipase A2.

1. In the present work the initially lowered oxidase activity of liver mitochondria of hibernating gophers is shown to increase upon Ca(2+)-loading, after freezing-thawing repeated three times and after swelling in a medium containing potassium acetate as well as in a hypotonic sucrose medium. 2. In all cases the inhibition of phospholipase A2 hindered the increase of the oxidase activity of mitochondria. 3. Mitochondria of hibernating gophers have a lowered delta psi in comparison with active animals, which is restored in the hypotonic medium.     

Analysis of the causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers, Citellus undulatus.

1. The causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers have been analysed. 2. The decrease of the ATP synthesis rate and suppression of the energy-dependent K(+)- and Ca(2+)-transport into mitochondria during hibernation has been found to be mainly related to a delta psi decrease in mitochondria of hibernating gophers. 3. The increase delta psi upon incubation of the mitochondria of hibernating animals in a hypotonic medium results in an essential acceleration of ATP synthesis and energy-dependent cationic transport.     

The protective properties of the endotoxin protein

The isolation and properties of endotoxin protein, or lipid A-associated protein (LAP), from Shigella sonnei were described earlier (Zh. mikrobiol. epidemiol. immunobiol., 1991, No. 4, pp. 11-17, and No. 7). In this report the data on its protective activity are presented. In experiments on mice one nanogram of LAP injected i. v. protected 50% of the animals against i. p. challenge with 40 LD50 of virulent S. sonnei. Guinea pigs injected s. c. with 10 micrograms of LAP were protected against local (keratoconjunctival) challenge with S. sonnei, the efficiency of immunization being 58%. LAP preparations containing no detectable amounts of O-antigen (less than 0.003%) were found to have a protective effect. Hyperimmune anti-LAP rabbit serum prevented local infection when incubated with S. sonnei challenge inoculum before injection into guinea pigs. Both active and passive protection induced by LAP was specific since no effect was observed in animals challenged with Shigella flexneri. In the homologous system the protective effect of anti-LAP serum was abolished by the addition of protein-free LPS. These results are compatible with the hypothesis that the protective activity of LAP depends on the presence of minute amounts of O-antigen whose immunogenic effect is greatly amplified by the protein component of the natural endotoxin complex.