Evanescent straight tapered-fiber coupling of ultra-high Q optomechanical micro-resonators in a low-vibration helium-4 exchange-gas cryostat.

We developed an apparatus to couple a 50-µm diameter whispering-gallery silica microtoroidal resonator in a helium-4 cryostat using a straight optical tapered-fiber at 1550 nm wavelength. On a top-loading probe specifically adapted for increased mechanical stability, we use a specifically-developed "cryotaper" to optically probe the cavity, allowing thus to record the calibrated mechanical spectrum of the optomechanical system at low temperatures. We then demonstrate excellent thermalization of a 63-MHz mechanical mode of a toroidal resonator down to the cryostat's base temperature of 1.65 K, thereby proving the viability of the cryogenic refrigeration via heat conduction through static low-pressure exchange gas. In the context of optomechanics, we therefore provide a versatile and powerful tool with state-of-the-art performances in optical coupling efficiency, mechanical stability, and cryogenic cooling.

Immunoassays for the detection of nicergoline and its metabolites in human plasma.

In order to determine nicergoline pharmacokinetics after oral administration to humans, we have developed two radioimmunoassays, one directed against nicergoline and the other directed against known nicergoline metabolites. The assays were validated according to the recommendations of international regulatory agencies and their limits of quantification were 40 and 10 pg/ml, respectively. In order to further validate the methods, a chromatographic separation of immunoreactive entities was performed with samples from healthy volunteers who were given 15 mg of Sermion (nicergoline orally administered). Chromatographic determination of assay specificity showed that the metabolite radioimmunoassay recognised known nicergoline metabolites but also a new metabolite. Using the antibodies directed against nicergoline, we were unable to detect nicergoline in the human plasma. This suggests that nicergoline is absent in the circulation because of complete metabolism through its first-pass effect.

High affinity of ergopeptides for cytochromes P450 3A. Importance of their peptide moiety for P450 recognition and hydroxylation of bromocriptine.

The interaction between rat and human liver cytochromes P450 with a series of lysergic acid derivatives and ergopeptide alkaloids was studied by difference visible spectroscopy. Ergopeptides, like bromocriptine, ergocryptine and dihydroergotamine, strongly interacted with rat liver microsomes with the appearance of a difference spectrum which is characteristic of their binding to a protein site close to the heme. The intensity of this spectrum was clearly dependent on the amounts of P450s 3A in the microsomes and was at its maximum in dexamethasone-treated rat microsomes. All the ergopeptides studied exhibited a high affinity for rat P450s 3A (Ks around 1 microM), although lysergic acid derivatives not bearing the tripeptide moiety failed to give significant interactions with these P450s. A cyclic azatripeptide exhibiting a structure very similar to that of the tripeptide moiety of ergopeptides also interacted with P450s 3A with appearance of an intense type I difference spectrum. Very similar results were observed with two allelic forms of human liver P450 3A4, P450 NF25 and P450 hPCN1, produced in yeast. In both cases all the ergopeptides studied showed high affinities for the P450s (Ks 0.6-2.2 microM) and an intense shift from the low-spin to the high-spin state upon substrate binding (60-100% spin shift). Lysergic acid derivatives not bearing the tripeptide group of ergopeptides also completely failed to interact with P450s 3A4. Liver microsomes from rats pretreated with dexamethasone, a specific inducer of P450 3A, were found to be particularly active for the hydroxylation of bromocriptine, which occurs at the level of its tripeptide moiety. Human liver microsomes as well as P450 NF25 and P450 hPCN1 also exhibited a high activity for bromocriptine hydroxylation at this level. These results show that ergopeptides exhibit a particularly high affinity for P450s of the 3A subfamily. The tripeptide moiety of ergopeptides is essential for their recognition by P450s 3A and binds at a site close to P450 heme, producing type-I difference spectra. Accordingly, at least one of the studied ergopeptides, bromocriptine, is hydroxylated by P450s 3A at the proline ring of the cyclopeptide moiety. As cyclosporine is known to be a good substrate of P450s 3A, these results suggest that P450s 3A may be especially prone in a general manner to recognize and oxidize peptides or pseudopeptides.

[The pharmacokinetics of dihydroergocristine after intravenous and oral administration in rats]. / Pharmakokinetik von Dihydroergocristin nach intravenöser und oraler Applikation bei Ratten.

The pharmacokinetic properties of dihydroergocristine (DHEC, CAS 17479-19-5) were investigated in rats using a specific radioimmunoassay technique specific for non-metabolized drugs. DHEC, administered intravenously at the dose of 6 mg/kg, showed a plasma profile conforming to an open two-compartment pharmacokinetic model with a long terminal half-life (t1/2 = 13.6 h). DHEC kinetics after oral administration (6 mg/kg) showed two peaks. The first peak (C = 37 micrograms/l) occurred at the first collection point (0.5 h) indicating a quick absorption of the drug. The second peak (C = 34 micrograms/l) occurred at 2 h and may be considered an indication of an enterohepatic cycle. A long terminal half-life (t1/2 = 18.1 h) was observed. An extensive biotransformation of DHEC was indicated by an almost complete absence of unchanged drug in the urine and a high systemic clearance (2.65 l.h-1 x kg-1). A large volume of distribution (52 l.kg-1) was calculated.

Metabolism of dihydroergotamine by a cytochrome P-450 similar to that involved in the metabolism of macrolide antibiotics.

1. Previous studies have shown that the macrolide antibiotics, such as oleandomycin and erythromycin, enhance their own transformation into a stable metabolite-cytochrome P-450 complex, thus impairing monooxygenase activity. This cytochrome P-450 induced by macrolides is similar to the major form induced in rats by pregnenolone-16 alpha-carbonitrile (PCN) (III A1 isozyme). 2. The cytochrome P-450 isozyme induced in rats by PCN or macrolide antibiotics bound dihydroergotamine (DHE) with high affinity and was also capable of metabolizing the drug. However, phenobarbital administration enhanced the metabolism of DHE to a greater extent than would be expected from the levels of the PB-PCNE isoenzyme, indicating that other cytochrome P-450 proteins may also be involved in DHE metabolism. 3. DHE metabolism was inhibited by macrolide antibiotics both ex vivo and in vitro. The metabolite-cytochrome P-450 complex formed by the antibiotics impairs the metabolism of DHE, so that when the complex is dissociated the metabolic activity is restored. These findings explain the observed clinical interactions between macrolides and other drugs, and such an approach may prove useful in their prediction.

Experimental evaluation of an unstable ring resonator with 90 degrees beam rotation: HiQ experimental results.

The first experimental results on a confocal unstable resonator with 90 degrees beam rotation (UR90 or HiQ) are presented. A beam quality of 1.06 was observed, and it varied by a maximum of 0.08 over a resonator misalignment range of 1 mrad. The outcoupled beam's polarization was circular. Reverse mode suppression was achieved on UR90 with a suppressed vs unsuppressed ratio of 115:1. Measurable reverse mode suppression was obtained with as little as 2% of the full reverse mode strength. Most of these results are compared with those for a conventional ring resonator.

[Bacterial contamination of the air in different operating rooms]. / Contamination bactérienne de l'air dans différentes salles d'opération.

Bacteria air samples were taken in the operating rooms, with no people present, to specify the level of air contamination and suggest bacteriological standards for different operating rooms. In the first step of this study, for 5 months the air contamination mean value of operating rooms, ventilated at 15 changes/hour was 18.5 Cfu/m3 +/- 1.9. In the second part of the study, during two years, 1 381 air samples were taken in 8 different operating rooms. The mean values of air contamination range from 1.4 Cfu/m3 in a Charnley isolator system to 121 Cfu/m3 in an operating room ventilated at 7.5 changes per hour. As a general rule, the airborne contamination is more significant in the oldest operating rooms than in the new one with filtrated air. The variations observed between 1981 and 1982 are explained by technical modifications of the system or progress in control of operating room conditions. Measurements of the bacterial contamination of the air give useful informations, but it is however better to ensure that the specifications for volume air supply and positive air pressure in the operating theatres are being fulfilled. The airborne bacterial concentration in a modern ventilated operating room should not exceed 30 Cfu/m3.

[Pain and inflammation of the foot in metabolic osteopathies : new causes of algodystrophy (author's transl)]. / Pied douloureus et inflammatoire des ostéopathies métaboliques. Nouvelles causes d'algodystrophie.

Three observations of patients with algodystrophia of the foot are reported. Biologic disorders suggestive of osteomalacia were found in two patients who recovered after receiving vitamin D. Cushing disease was diagnosed in the remaining patient ; again algodystrophia disappeared after specific therapy was given. The few similar cases published in the medical literature are reviewed. Attention is drawn to their misleading nature. Most published cases occurred with osteomalacia or endocrinic osteopathy. Such conditions should be looked for in all patients with apparently primary algodystrophia of a lower limb.

[Nutritional value of fish flours made in laboratory from fishes of the Nosy-Bé area]. / Valeur alimentaire de farines fabriquées en laboratoire à partir de poissons de la région de Nosy-Bé.

Several types of fish meals (principally from no commercializable Carangues) are made in a laboratory. They are tested for general composition, amino-acid composition, vitamin and mineral compositions. Two fish meals from Carangues are very interesting: they are white muscle meal (rich in proteins of good quality, poor in lipids and slightly rich in minerals) and the meal from fish without head and guts (not so rich in proteins but slightly richer in minerals). These fish meals have a variable interest regarding mineral and vitamin contents. All of them have a lack of methionin and cystin which is comparable to the defficiency mentioned in other fish meals by various authors.