Prevalence of type 2 diabetes and other cardiovascular risk factors in Mayotte in 2008: the MAYDIA study.

AIM: Mayotte, a French overseas territory located in the Indian Ocean, has never had a previous estimate of diabetes prevalence, but has recently undergone socioeconomic changes leading to lifestyle modifications. For this reason, a survey was carried out in 2008 to estimate the prevalence of diabetes and cardiovascular risk factors in the island's population. METHODS: A three-step, randomized sample of 1268 individuals, aged 30-69 years, was home-screened, using capillary blood glucose and capillary HbA(1c), weight, height, waist circumference and two blood-pressure measurements. Those with a history of diabetes, glucose ≥1 g/L (fasting) or ≥1.40 g/L (non-fasting), or HbA(1c)≥6%, and a subgroup of those with normal results were examined at a healthcare centre to measure venous HbA(1c) and glucose, and to diagnose diabetes, using an oral glucose tolerance test. RESULTS: The weighted prevalence of diabetes (venous plasma glucose ≥1.26 g/L at fasting and/or ≥2 g/L at 2 h, or treatment with oral hypoglycaemic agents or insulin) was 10.5% (95% CI: 8.2-13.4%). This increased with age from 3% at age 30-39 years to 26% at age 60-69 years, with no gender differences. Also, more than 50% of those with diabetes were unaware of it, while half of those treated for diabetes still had HbA(1c) levels >7%. The prevalence of overweight (BMI: 25-29 kg/m(2)) was estimated to be 35% in men and 32% in women, while obesity (≥30 kg/m(2)) was estimated to be 17% in men and 47% in women. CONCLUSION: The high prevalence of obesity combined with a high prevalence of diabetes indicates a potential for further increases in the prevalence of diabetes and cardiovascular disease in Mayotte. Preventative action against obesity, diabetes and hypertension is required now, as well as plans for appropriate healthcare delivery in the island.

Dynamic behavior of an injection-locked quantum-dash Fabry-Perot laser at zero-detuning.

This work investigates the behavior of a zero-detuned optically-injected quantum-dash Fabry-Perot laser as the injected field ratio is increased from near-zero to levels resulting in stable locking. Using a normalized model describing optically-injected semiconductor lasers, variations in the slave laser's free-running characteristics are shown to have a strong impact on the coupled system's behavior. The theoretical model is verified experimentally using a high resolution spectrometer. It is found that the quantum-dash laser has the technological advantage of a low linewidth enhancement factor at low bias currents that suppresses undesirable Period-2 and chaotic behavior. Such observations suggest that optically-injected quantum-dash lasers can be used as an enabling component for tunable photonic oscillators.

The role of CD47 in neutrophil transmigration. Increased rate of migration correlates with increased cell surface expression of CD47.

CD47, a cell surface glycoprotein, plays an important role in modulating neutrophil (PMN) migration across endothelial and epithelial monolayers. Here we show that anti-CD47 monoclonal antibodies (mAbs) delay PMN migration across collagen-coated filters or T84 epithelial monolayers toward the chemoattractant formylmethionylleucylphenylalanine (fMLP). Despite delayed transmigration by anti-CD47 mAbs, the numbers of PMN migrating across in either condition were the same as in the presence of control non-inhibitory mAbs. Cell surface labeling and immunoprecipitation demonstrated upregulation of CD47 to the PMN cell surface with kinetics similar to those of the transmigration response. Subcellular fractionation studies revealed redistribution of CD47 from intracellular compartments that co-sediment with secondary granules to plasma membrane-containing fractions after fMLP stimulation. Experiments performed to investigate potential signaling pathways revealed that inhibition of tyrosine phosphorylation with genistein reversed the anti-CD47-mediated PMN migration delay, whereas inhibition of phosphatidylinositol 3-kinase only partially reversed anti-CD47 effects that correlated with a rapid increase in PMN cell surface CD47. Analysis of the contribution of epithelial-expressed CD47 to PMN transmigration revealed that PMN migration across CD47-deficient epithelial monolayers (CaCO2) was significantly increased after stable transfection with CD47. These results suggest that cell surface CD47 and downstream tyrosine phosphorylation signaling events regulate, in part, the rate of PMN migration during the inflammatory response.

Neutrophil transepithelial migration: regulation at the apical epithelial surface by Fc-mediated events.

Neutrophil (PMN) transepithelial migration is a major effector of epithelial defense in inflammatory diseases involving mucosal surfaces. However, major receptor-ligand interactions between epithelial cells and PMN remain incompletely characterized. To better define the molecular events involved in PMN interactions with epithelial cells, we produced a monoclonal antibody called g82 that inhibited PMN transepithelial migration in the physiological basolateral-to-apical direction. The g82 antigen localized to the apical surface of human colonic epithelium and was significantly upregulated under inflammatory conditions. Immunoprecipitation revealed two polypeptides of M(r) 207 and 32 kDa. F(ab')(2) fragments from g82 IgG had no effect on transmigration, suggesting Fc dependence. Further experiments confirmed dependence on the PMN Fc receptor CD32A and that the observed effects were secondary to a failure of PMN to detach from the apical epithelial surface. These Fc-mediated events were epitope specific since binding, isotype-matched antibodies did not affect detachment. These results identify a new mechanism for retention of PMN at the apical epithelial surface following transepithelial migration. This pathway may be important in pathogen clearance and mucosal pathophysiology associated with autoimmunity.

Human junction adhesion molecule regulates tight junction resealing in epithelia.

Epithelial cells form a highly selective barrier and line many organs. The epithelial barrier is maintained by closely apposed cell-cell contacts containing tight junctions, the regulation of which is incompletely understood. Here we report the cloning, tissue localization and evidence for a role in epithelial barrier regulation of an immunoglobulin superfamily member that likely represents the human homolog of murine junction adhesion molecule (JAM). Analysis of the primary structure of human JAM, cloned from T84 epithelial cells, predicts a transmembrane protein with an extracellular domain that contains two IgV loops. Monoclonal antibodies generated against the putative extracellular domain were reactive with a 35-39 kDa protein from both T84 epithelial cells and human neutrophils. By immunofluorescence, JAM mAbs labeled epithelial cells from intestine, lung, and kidney, prominently in the region of tight junctions (co-localization with occludin) and also along lateral cell membranes below the tight junctions. Flow cytometric studies confirmed predominant JAM expression in epithelial cells but also revealed expression on endothelial and hematopoietic cells of all lineages. Functional studies demonstrated that JAM specific mAbs markedly inhibited transepithelial resistance recovery of T84 monolayers after disruption of intercellular junctions (including tight junctions) by transient calcium depletion. Morphologic analysis revealed that, after disassembly of cell-cell junctions, anti-JAM inhibition of barrier function recovery correlated with a loss of both occludin and JAM, but not ZO-1, in reassembling tight junction structure. Reassembly of the major adherens junction component E-cadherin was not affected by JAM specific mAbs. Our findings suggest that JAM plays an important role in the regulation of tight junction assembly in epithelia. Furthermore, these JAM-mediated effects may occur by either direct, or indirect interactions with occludin.

Characterization of fatty acid synthase in cell lines derived from experimental mammary tumors.

The lipogenic enzyme fatty acid synthase (FAS) is elevated in various human primary cancers and certain human cancer cell lines. FAS overexpression in human neoplasia has clinical relevance because of its association with tumor aggression and potential chemotherapeutic intervention. Here, we surveyed FAS in cell lines established from normal murine mammary epithelium (NMuMG) and from mammary tumors induced by either rodent polyoma (Py) virus or murine mammary tumor virus (MMTV). Western blotting revealed greater content of FAS in Py-transformed A1-1 and T1 than NMuMG or MMTV-transformed Mm5MT, RIIIMT and MMT060562. These data suggest that signaling events mediated by Py transformation may increase cellular amounts of FAS. Although FAS content was elevated to similar levels in A1-1 and T1, specific activities were significantly different as enzyme activity in T1 was 3-fold higher than A1-1. Likewise, FAS activity in NMuMG was about 0.5-fold higher than the MMTV-transformed lines, even though enzyme content was similar. Immunoprecipitation studies employing anti-phosphoamino acid antibodies followed by immunoblot analysis with anti-FAS antisera (and vice versa) were used to characterize the constitutive phosphorylation state of the enzyme. Phosphoserine and phosphothreonine residues were detected in the more active FAS from T1 and NMuMG, but not in the less active FAS from Mm5MT or A1-1. Discovery of phosphorylated FAS suggests that the enzyme may have more immediate control over lipogenesis than previously thought. High-dose (10-4 M) dexamethasone induced FAS content and activity in NMuMG and MMTV-transformed lines but not Py-transformed cells. Lower concentrations (10-8, 10-6 M) of dexamethasone also activated FAS but without concomitant elevation of its protein content, which was consistent with a phosphorylated form of FAS. Finally, cell lines were treated with the FAS inhibitor cerulenin: almost all breast cancer lines were growth inhibited at significantly lower amounts of drug than normal cell lineages, suggesting that FAS plays a greater role in viability of tumor cells than normal cells. Pretreatment with palmitate (a primary end-product of FAS) prior to cerulenin rescued A1-1 cells only slightly from growth inhibition, whereas pretreatment with oleate (a monounsaturated fatty acid synthesized from palmitate) synergized cerulenin's cytotoxic effects.

Endometriosis-associated infertility: evaluation of preoperative use of danazol, gestrinone, and buserelin.

In order to assess adequately the effectiveness of danazol, Gestrinone, and Buserelin, a prospective nonrandomized study was initiated in 126 patients with laparoscopically confirmed ovarian endometriosis. After hormonal therapy, laparotomy with microsurgical resection of endometriotic cysts was carried out. Regression (greater than 25%) of ovarian endometriosis was noted in 30%, 34%, and 73% of cases after danazol, Gestrinone, and Buserelin, respectively. The pregnancy rate in moderate endometriosis (53%) differed significantly from the rate obtained in severe endometriosis (45%). The highest percentages were found after Buserelin therapy. In conclusion, Buserelin emerged superior to danazol or Gestrinone treatment. Nevertheless, hormonal treatment leads to an incomplete suppression of ovarian endometriotic implants and this suggests the necessity of surgically removing invasive ovarian endometriosis.

Administration of nasal Buserelin as compared with subcutaneous Buserelin implant for endometriosis.

One hundred infertile patients with laparoscopically confirmed ovarian endometriosis were treated with either intranasal (IN) Buserelin (Hoechst, AG, Frankfurt am Main, West Germany) (300 micrograms three times a day) or subcutaneous (SC) Buserelin implant (6.6 mg Buserelin). Serum estradiol was suppressed in the menopausal range in both groups, but the inhibition of the pituitary ovarian axis appeared more profound and consistent in the SC group than in the IN group. Laparoscopic findings proved that the SC Buserelin emerged superior to the IN Buserelin. Indeed, the score of endometriotic lesions and the ovarian cyst diameter were more reduced in the SC group than in the IN group. Moreover, the histologic study showed a lower incidence of active endometriosis and a lower mitotic index of ovarian endometrial epithelium in the SC group than in the IN group. In conclusion, the release of a gonadotropin-releasing hormone agonist by a biodegradable implant achieved better efficacy in reducing endometriotic lesions than the IN mode of administration.

Histologic study of ovarian endometriosis after hormonal therapy.

To evaluate the persistence of endometriosis and the morphologic changes occurring in endometriotic foci after hormonal therapy, microsurgical resection of ovarian endometriosis was performed in 148 women. After hormonal therapy (n = 116), a high prevalence of active endometriosis without signs of degeneration was found. Mitotic index was similar in the group of untreated women (n = 32) and in the three groups of women treated either with lynestrenol (Organon, Oss, The Netherlands), gestrinone (Roussel UCLAF, Paris, France), or buserelin (Hoechst, Frankfurt, West Germany). In conclusion, hormonal treatment leads to an incomplete suppression of endometriotic foci.

Combined (hormonal and microsurgical) therapy in infertile women with endometriosis.

Fifty patients with moderate or severe endometriosis received 5 mg/day lynestrenol for 6 months prior to microsurgery. A significant regression of the ovarian and peritoneal implants was observed in 72% of the cases after progestative treatment, but the presence of residual epithelium in all cases made surgical resection necessary. After preoperative medical treatment and microsurgery, intrauterine (living births) pregnancy rates of 60 and 47% were obtained in cases of moderate and severe endometriosis, respectively. The following prognostic factors were found in this series: the degree of endometriosis, the concomitant male factors, the decrease of endometriotic lesions after treatment, and the unilaterality of ovarian endometriosis.

Surgical management of tubal obstruction at the uterotubal junction.

The advantages of microsurgical anastomosis for cornual occlusion are evaluated in a series of 82 pure cases of pathologic cornual occlusion. The term pregnancy rate was 44% and the ectopic pregnancy rate was 7%. The following factors were found influencing the pregnancy rate: maximized tubal length; preserved intramural portion; absence of chronic inflammation; absence of tubal inclusions; absence of tubal endometriosis.