Apport de l'angiographie au vert d'indocyanine (ICG) dans la localisation des néovascularisations chororoidiennes occultes [Value of indocyanine green angiography in localization of occult choroid neovascularization]

PURPOSE: To determine the role of Indocyanin Green (ICG) angiography in localizing occult new vessels associated with age-related macular degeneration (ARMD) and assess the possibilities of ICG guided laser photocoagulations. PATIENTS AND METHODS: Fluorescein and ICG angiographies (IMAGEnet system) of 62 patients with occult new vessels (ONV), serous (SPED) or vascular (VPED) pigment epithelium detachment have been studied. RESULTS: Based on fondoscopic examination and fluorescein angiography, 43 eyes (69%) disclosed ONV, 8 (13%) SPED and 11 (18%) VPED. Choroidal neovascularisation was confirmed by ICG angiography in 37 ONV cases (86%), in 8 (72%) VPED cases, but in no SPED. Conversion of ONV in classical neovascular membranes was possible in 19 ONV cases (44%) and in 6 (54%) VPED cases, making a laser photocoagulation possible in 9 eyes (36%). CONCLUSION: ICG angiography plays an important role in the evaluation, classification and laser treatment of patients with ONV secondary to ARMD.

Microsatellite variation reveals low genetic subdivision in a chromosome race of Sorex araneus (Mammalia, Insectivora)

Two hundred and forty-five individuals of the common shrew (Sorex araneus, Insectivora, Mammalia) from 24 sampling localities situated in four different valleys of the western European Alps were genotyped for six microsatellite loci. Allelic variability ranged from 3 to 32 different alleles at a single locus and the average gene diversity over all loci was 0.69. An analysis for F and R statistics revealed weak genetic population subdivision (Fst = 0.032; Rst = 0.016). This suggests considerable gene flow and little phylogeographic structure within and between valleys. We tested whether a stepwise mutation model (SMM) better explained variation at the microsatellite loci than an infinite allele model (IAM). No trend in favor of either model was detected.

Loss of Memo, a novel FGFR regulator, results in reduced lifespan.

Memo is a widely expressed 33-kDa protein required for heregulin (HRG)-, epidermal growth factor (EGF)-, and fibroblast growth factor (FGF)-induced cell motility. Studies in mouse embryonic fibroblasts, wild-type or knockout for Memo, were performed to further investigate the role of Memo downstream of FGFR. We demonstrated that Memo associates with the FGFR signalosome and is necessary for optimal activation of signaling. To uncover Memo's physiological role, Memo conditional-knockout mice were generated. These animals showed a reduced life span, increased insulin sensitivity, small stature, graying hair, alopecia, kyphosis, loss of subcutaneous fat, and loss of spermatozoa in the epididymis. Memo-knockout mice also have elevated serum levels of active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), and calcium compared to control littermates expressing Memo. In summary, the results from in vivo and in vitro models support the hypothesis that Memo is a novel regulator of FGFR signaling with a role in controlling 1,25(OH)2D production and normal calcium homeostasis.

Comparative effects of GLP-1-(7-36) amide, oxyntomodulin and glucagon on rabbit gastric parietal cell function.

We have investigated in vitro, the effects of glucagon-like peptide-1-(7-36) amide (GLP-1-(7-36) amide), oxyntomodulin and glucagon on two rabbit parietal cell-enriched fractions (F3, F3n), with parietal cell contents of 60% and 88%, respectively. Histamine (10(-5) M) stimulated [14C]aminopyrine accumulation to an amount of 850% in excess of the basal level, whereas GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-6) M) induced increases of 50% and 30%, respectively. With a histamine concentration of 10(-6) M, [14C]aminopyrine accumulation was stimulated to 498% in excess of the basal level; GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-7) M) induced increases of 18% and 15%, respectively. With these parameters, oxyntomodulin[19-37] and glucagon were without effect. Specific binding of [125I]GLP-1-(7-36) amide to parietal cell plasma membranes was inhibited dose-dependently by GLP-1-(7-36) amide, oxyntomodulin and glucagon with inhibitory concentrations of 0.25 nM, 65 nM and 800 nM, respectively. No specific binding of [125I]oxyntomodulin or [125I]glucagon was detectable. GLP-1-(7-36) amide receptor mRNA was only detected in parietal cell-enriched fractions. GLP-1-(7-36) amide, oxyntomodulin and glucagon stimulated parietal cell cAMP production to similar maximal levels with median values close to 0.28 nM, 10.5 nM and 331.7 nM, whereas oxyntomodulin[19-37] had no effect. The maximal cAMP production induced by GLP-1-(7-36) amide, oxyntomodulin or glucagon was additive to that induced by histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Routine therapeutic drug monitoring in patients treated with 10-360 mg/day citalopram

From data collected during routine TDM, plasma concentrations of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were measured in 345 plasma samples collected in steady-state conditions. They were from 258 patients treated with usual doses (20-60 mg/d) and from patients medicated with 80-360 mg/d CIT. Most patients had one or several comedications, including other antidepressants, antipsychotics, lithium, anticonvulsants, psychostimulants and somatic medications. Dose-corrected CIT plasma concentrations (C/D ratio) were 2.51 +/- 2.25 ng mL-1 mg-1 (n = 258; mean +/- SD). Patients >65 years had significantly higher dose-corrected CIT plasma concentrations (n = 56; 3.08 +/- 1.35 ng mL-1 mg-1) than younger patients (n = 195; 2.35 +/- 2.46 ng mL-1 mg-1) (P = 0.03). CIT plasma concentrations in the generally recommended dose range were [mean +/- SD, (median)]: 57 +/- 64 (45) ng/mL (10-20 mg/d; n = 64), 117 +/- 95 (91) ng/mL (21-60 mg/d; n = 96). At higher than usual doses, the following concentrations of CIT were measured: 61-120 mg/d CIT, 211 +/- 103 (190) ng/mL (n = 93); 121-200 mg/d: 339 +/- 143 (322) ng/mL (n = 70); 201-280 mg/d: 700 +/- 408 (565) ng/mL (n = 18); 281-360 mg/d: 888 +/- 620 (616) ng/mL (n = 4). When only one sample per patient (at the highest daily dose if repeated dosages) is considered, there is a linear and significant correlation (n = 48, r = 0.730; P < 0.001) between daily dose (10-200 mg/d) and CIT plasma concentrations. In experiments with dogs, DDCIT was reported to affect the QT interval when present at concentrations >300 ng/mL. In this study, DDCIT concentration reached 100 ng/mL in a patient treated with 280 mg/d CIT. Twelve other patients treated with 140-320 mg/d CIT had plasma concentrations of DDCIT within the range 52-73 ng/mL. In a subgroup comprised of patients treated with > or =160 mg/d CIT and with CIT plasma concentrations < or =300 ng/mL, and patients treated with < or =200 mg/d CIT and CIT plasma concentrations > or = 600 ng/mL, the enantiomers of CIT and DCIT were also analyzed. The highest S-CIT concentration measured in this subgroup was 327 ng/mL in a patient treated with 140 mg/d CIT, but the highest S-CIT concentration (632 ng/mL) was measured in patient treated with 360 mg/d CIT. In conclusion, there is a highly linear correlation between CIT plasma concentrations and CIT doses, well above the usual dose range.

Characterization of spontaneous gacS and gacA regulatory mutants of Pseudomonas fluorescens biocontrol strain CHAO.

In Pseudomonasfluorescens strain CHAO, the response regulator gene gacA controls expression of extracellular enzymes and antifungal secondary metabolites, which are important for this strain's biocontrol activity in the plant rhizosphere. Two Tn5 insertion mutants of strain CHA0 that had the same pleiotropic phenotype as gacA mutants were complemented by the gacS sensor kinase gene of P. syringae pv. syringae as well as that of P. fluorescens strain Pf-5, indicating that both transposon insertions had occurred in the gacS gene of strain CHA0. This conclusion was supported by Southern hybridisation using a gacS probe from strain Pf-5. Overexpression of the wild-type gacA gene partially compensated for the gacS mutation, however, the overexpressed gacA gene was not stably maintained, suggesting that this is deleterious to the bacterium. Strain CHA0 grown to stationary phase in nutrient-rich liquid media for several days accumulated spontaneous pleiotropic mutants to levels representing 1.25% of the population; all mutants lacked key antifungal metabolites and extracellular protease. Half of 44 spontaneous mutants tested were complemented by gacS, the other half were restored by gacA. Independent point and deletion mutations arose at different sites in the gacA gene. In competition experiments with mixtures of the wild type and a gacA mutant incubated in nutrient-rich broth, the mutant population temporarily increased as the wild type decreased. In conclusion, loss of gacA function can confer a selective advantage on strain CHA0 under laboratory conditions.

[Illustrations de Rome et l'Italie méridionale.] / J.D. Harding, dess. ; L. De Sivry, aut. du texte

Comprend : [pl. en reg. de la page de titre : vue du Château Saint-Ange, du pont des Anges et du Tibre à Rome. [Cote K 1728/Microfilm R 122016] ; [Fig. au titre : vue de la ville de Sorrente.] Sorrente. [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.17 :] Rome (Vue de l'Eglise St-Pierre et de la Place du Vatican). [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.27. Chapitre III : Saint-Pierre de Rome.] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.49 : le Forum de Rome.] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.197. Chapitre XII : vue de Tivoli.] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.247. Chapitre XIV : paysage du Sud de l'Italie. Environs de Naples avec vue sur le Golfe.] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.264 : Naples et le Pausilippe (tombeau de Viegile) et la plage de la Mergellina.] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.276 : paysage du lac Lucrin et le Monte-Nuovo (?) qui jaillit en une nuit, en 1538, d'une éruption volcanique et engloutit le village de Tripergola] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.279 : une île du Golfe de Naples (Ischia?).] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.296 : vue de l'intérieur de l'église du Carmine à Naples] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.305 : vue d'Herculanum] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.327 : vue d'Amalfi et de son couvent des Capucins suspendu aux flancs de la montagne.] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.331. Chapitre XX : vue de vestiges de temples antiques dans la région de Paestum (?).] [Cote K 1728/Microfilm R 122016] ; [pl. en reg. p.339 : vue du Couvent de Saint-Martin, non loin de Palerme, en Sicile.] [Cote K 1728/Microfilm R 122016]