The 21-dehydroxylation of corticosteroids: evidence for an enol intermediate and the hydroxylation of steroids by fungal cyto-chrome P450: evidence for a stepwise mechanism

Two enzyme mechanisms were examined: the 21-dehydroxylation of corticosteroids by the anaerobe Eubacterium l en tum, and the hydroxylation of steroids by fungal cytochrome P450. Deuterium labelling techniques were used to study the enzymic dehydroxylation. Corticosteroids doubly labelled (2H) at the C-21 position were incubated with a culture of Eubacterium lentum. It was found that t he enzymic dehydroxylation proceeded with the loss of one 2H f rom C-21 per molecule of substrate. The kinetic isotope ef fect f or the reaction was found to be k~kD = 2. 28. These results suggest that enzyme/substr ate binding in this case may proceed via t he enol form of the substrate. Also , it appears that this binding is, at least in part, the rate determining step of t he reaction. The hydroxylation of steroids by fungal cytochrome P450 was examined by means of a product study. Steroids with a double bond at the A8 (9), ~( lO ), or ~ (ll) position were synthesized. These steroids were then incubated with fungal strains known to use a cytochrome P450 monooxygenase to hydroxylate at positions allylic to these doubl e bonds. The products formed in these incubations indicated that the double bonds had migrated during allylic hydroxylat ion. This suggests that a carbon centred radical or ion may be an intermediate i n the cytochrome P450 cat alytic cycle.

The 21-dehydroxglation of corticosteroids of Eubacterium lentum and the dehalogenation of 4-chlorobenzoic acid by 4-chlorobenzoate dehalogenase

Two enzyme mechanisms were investigated: the 21-dehydroxylation of corticosteroids by Eubacterium lentum and the dehalogenation of 4-chlorobenzoic acid by Pseudomonas sp. CBS 3. , Chemical and enzymic methods of reduction of 21-oxo steroids were used to generate C-21-d1 compounds of tetrahydrodeoxycorticosterone, with both predominant stereochemistries. It was found that during the dehydroxylation the pro-S hydrogen at the C-21 position was lost preferentially. This suggests that the enzyme removes the pro-S hydrogen during binding to the active site as the ene-diol. To study the hydrolytic replacement of chlorine by hydroxyl , p-chlorobenzoic acid-d4 was prepared and sent to Germany for an ~ncubation with an enzyme preparation of 4-Chlorobenzo~te Dehalogenase. Results suggests the possible loss of deuterium during the conversion of p-chlorobenzoate to p-hydroxybenzoate, from all four ring positions. Many methods of preparing the control compound p-hydroxybenzoic acid-d4 were investigated.

Traité du microscope : son mode d'emplot; ses applications a l'etude des injections; a l'anatomie humaine et comparée; a la pathologie médico-chirurgicale a l'histoire naturelle animale et vegetale et a l'economie agricole

UANL

Suboptimal use of inhaled corticosteroids in children with persistent asthma : inadequate physician prescription, poor patient adherence or both ?

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Transforaminal versus intra-articular facet steroid injections for the treatment of cervical radiculopathy : a randomized, double-blinded, controlled study.

Cette étude a été subventionnée par le Fonds de recherche du Québec - Santé (FRQ-S, grant # 21230 – 2)

The impact of early intra-articular corticosteroid injections on the outcome of oligoarticular juvenile idiopathic arthritis

Contexte Un objectif important de la prise en charge de l'arthrite juvénile oligoarticulaire serait d'altérer le cours de la maladie à l'aide d'une thérapie hâtive. Nous avons étudié l'effet des injections intra-articulaires de corticostéroïdes hâtives sur les chances d'atteindre un décompte d'articulation active de zéro et une maladie inactive. Méthode Les données démographiques, cliniques et thérapeutiques des patients avec oligoarthrite juvénile enrôlés dans une étude prospective longitudinale pancanadienne ont été collectées pendant 2 ans. Une injection hâtive était définie comme étant reçue dans les 3 premiers mois suivant le diagnostic. Les équations d'estimation généralisées ont été utilisées pour l'analyse statistique. Résultats Trois cent dix patients ont été inclus. Cent onze (35.8%) ont reçu une injection hâtive. Ces derniers avaient une maladie plus active lors de l'entrée dans l'étude. Les patients exposés à une injection hâtive avaient une chance similaire d'obtenir un décompte d'articulation active de zéro, OR 1.52 (IC95% 0.68-3.37), p=0.306 mais étaient significativement moins à risque d'avoir une maladie inactive, OR 0.35 (IC95% 0.14-0.88), p=0.026. Interprétation Dans cette cohorte de 310 patients avec oligoarthrite juvénile, les injections hâtives de corticostéroïdes n'ont pas mené à une probabilité plus élevée d'atteindre un décompte d'articulation active de zéro ou une maladie inactive. Des problématiques méthodologiques intrinsèques à l'utilisation de données observationnelles pour fins d'estimation d'effets thérapeutiques auraient pu biaiser les résultats. Nous ne pouvons affirmer avec certitude que les injections hâtives n'améliorent pas le décours de la maladie. Des études prospectives adressant les limitations soulevées seront requises pour clarifier la question.

Soil injections of carbohydrates improve fine root growth of established urban trees

Four established mature tree species (Aesculus hippocastanum L., Betula pendula Roth., Primus avium L. and Quercus rohur L.) commonly planted in UK urban landscapes were subjected to soil injections of the carbohydrate sucrose at 25, 50 and 70g per litre of water. Fine root dry weight was recorded at month 5 following soil injections. Soil injections of sucrose significantly increased fine root dry weight compared to controls, however; growth responses were influenced by species and the concentration of sucrose applied. Results indicate soil injections of sucrose ≥ 50g litre of water may be able to improve root growth of established mature trees. Such a response is desirable as root damage following construction is a frequent problem encountered by established trees growing in UK towns and cities.

EISCAT/CRRES observations: nightside ionospheric ion outflow and oxygen-rich substorm injections

We present combined observations made near midnight by the EISCAT radar, all-sky cameras and the combined released and radiation efects satellite (CRRES) shortly before and during a substorm. In particular, we study a discrete, equatorward-drifting auroral arc, seen several degrees poleward of the onset region. The arc passes through the field-aligned beam of the EISCAT radar and is seen to be associated with a considerable upflow of ionospheric plasma. During the substorm, the CRRES satellite observed two major injections, 17 min apart, the second of which was dominated by O+ ions. We show that the observed are was in a suitable location in both latitude and MLT to have fed O+ ions into the second injection and that the upward flux of ions associated with it was sufficient to explain the observed injection. We interpret these data as showing that arcs in the nightside plasma-sheet boundary layer could be the source of O+ ions energised by a dipolarisation of the mid- and near-Earth tail, as opposed to ions ejected from the dayside ionosphere in the cleft ion fountain.

Overlapping cusp ion injections: An explanation invoking magnetopause reconnection

An explanation of overlapping cusp ion injections is presented using the pulsating cusp model of the effects of magnetopause reconnection. It is shown that two populations of cusp ions, covering separated energy ranges, can be seen simultaneously by low- or mid-altitude satellites because of the combined effect of the acceleration and the straightening of newly-opened field lines as they evolve away from the reconnection site. Observations of such signatures, recently reported in data from the Viking and Freja satellites, are discussed in terms of pulsed and steady reconnection.

Single vs. two steroid injections for carpal tunnel syndrome: a randomised clinical trial

We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome (CTS) in a randomised double-blind controlled trial. Patients with idiopathic CTS were randomised into (i) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and (ii) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks. The primary outcome was the Global Symptom Score (GSS). Forty patients were recruited. By 40 weeks, the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group, but there was no significant difference in GSS between the two groups (p = 0.26). There were also no significant differences in terms of electrophysiological and functional outcomes. The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief.

Safer injections, fewer infections : management of needles and sharps and occupational blood exposure in rural north Indian health settings

This study investigated injection practices and occupational exposure to blood in rural north Indian health settings. The findings highlighted a range of practices potentially contributing to the transmission of hepatitis and HIV to both patients and staff in these settings. Interventions need to focus on the development of organisational structures to support and facilitate safer practices.