Effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes in an animal model of type 2 diabetes.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates blood glucose level post-prandially. It has been proposed that GLP-1 can be used in type 2 diabetes (T2D) mellitus treatment because of its insulinotropic action. Despite its remarkable advantages, GLP-1 suffers the disadvantage of an extremely short half-life owing to its degradation by the dipeptidyl peptidase IV protease. One way of overcoming this drawback is GLP-1 gene delivery. Here we show effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes (TNCs) in Zucker diabetic fatty (ZDF) animal model of T2D. The expression plasmid fused the GLP-1 gene to a Furin cleavage site was driven by a cytomegalovirus promoter/enhancer. TNCs were prepared by mixing this plasmid with chitosans of specific molecular weight (MW), degree of deacetylation (DDA) and ratio of chitosan amine to DNA phosphate (N:P ratio). Animals injected with the TNC chitosan 92-10-5 (DDA-MW-N:P) showed GLP-1 plasma levels of about fivefold higher than that in non-treated animals and the insulinotropic effect of recombinant GLP-1 was shown by a threefold increase in plasma insulin concentration when compared with untreated animals. Intraperitoneal glucose tolerance tests revealed an efficacious decrease of blood glucose compared with controls for up to 24 days after treatment, where injections of this formulation allowed near-normalization of blood glucose level. TNCs composed of specific chitosans and GLP-1-expressing plasmid constructs showed an impressive ability to harness the profound therapeutic potential of GLP-1 for the treatment of T2D mellitus.

Effect of narghile and cigarette smoking on newborn birthweight.

OBJECTIVE: To assess the effect of narghile smoking on the weight of newborns. DESIGN: Historical retrospective cohort. SETTING: Six major hospitals in Greater Beirut, Lebanon. POPULATION: Consecutive singleton newborns delivered from August 2000 to August 2003. METHODS: Obstetric and nursery charts were reviewed to obtain information about maternal and neonatal variables. Information concerning initiation of smoking, dose of smoking, smoking habits during pregnancy, and socio-demographic characteristics was collected through interviews with mothers. MAIN OUTCOME MEASURES: Low birthweight and newborn birthweight. RESULTS: Exclusive narghile smokers constituted 4.4% (378/8592) of women. Multiparas were significantly more likely to smoke cigarettes and narghile. Mothers smoking narghile more than once per day were at 2.4 increased odds of having low birthweight infants compared with nonsmoking mothers (OR 2.4; 95% CI 1.2-5.0) after adjusting for confounding variables. No difference was noted between women smoking narghile in the first trimester and those initiating smoking in subsequent trimesters regarding low birthweight. CONCLUSIONS: Narghile smoking more than once per day increases the odds of low birthweight by a 2.4-fold compared with nonsmokers, although to a lesser extent than cigarette smoking.

Low socioeconomic status and neonatal outcomes in an urban population in a developing country.

OBJECTIVE: To investigate the effect of low socioeconomic status indicators, specifically parental educational and occupational characteristics on neonatal health outcomes. METHODS: Analysis of 3372 newborn infants admitted to five National Collaborative Perinatal Neonatal Network centers (1 February 2000 to 31 January 2002). Outcomes included birth weight, gestational age, admission to the neonatal intensive care unit (NICU) and length of hospital stay. The independent effects of mother's education and occupation as well as father's occupation on health outcomes were assessed by means of stepwise logistic regression analysis. RESULTS: A total of 271 (8.0%) infants were of low birth weight, 306 (9.1%) were preterm, 410 (12.2%) had NICU admissions and 240 (7.1%) were hospitalized for more than a week. After adjusting for maternal gravidity, age, smoking during pregnancy and pregnancy-related complications, parental socioeconomic characteristics had no significant impact on low birth weight or preterm birth. NICU admission and prolonged hospitalization were significantly correlated with skilled, semi-skilled and unskilled paternal occupations. Illiterate mothers had nearly 3-5 times the risk of NICU admission and prolonged hospitalization. CONCLUSION: Both father's occupation and mother's education play an important role as determinants of neonatal morbidity characteristics.

[Biomechanical study of the ankle joint]. / Contribution à létude biomécanique de la pince malléolaire.

The authors have studied the transmission of body weight in several positions. Two methods have been used - strain gauges and injection of dye into the joint capsules to show areas with contact during weight-bearing and non weight-bearing. The findings have shown the role of the fibula and of both malleoli during weight-bearing which causes a noticeable increase in the area of surface contact. The lateral aspect of the talus and the medial aspect of the lateral malleolus are always in contact in any position of the talus. The fundamental role of the tibio-fibular ligaments in the mechanics of the ankle is demonstrated.