A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.     

Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response.     

Plasma thymulin and nerve growth factor levels in patients with primary open angle glaucoma and elevated intraocular pressure

Background The objective was to measure the plasma concentrations of thymulin and nerve growth factor (NGF) in a group of patients with primary open angle glaucoma (POAG) and compare them with age- and sex-matched normal controls.Methods Twenty-eight patients newly diagnosed with POAG who were not undergoing treatment were compared with the same number of age- and sex-matched healthy controls. Blood samples were drawn into heparinized tubes and plasma samples were collected for the determination of the concentrations of thymulin and NGF, using specific enzyme-linked immunosorbent assay (ELISA). The Student’s t test was used to perform the necessary statistical analysis of the results.Results Seventeen women and 11 men were enrolled in each of the two groups (study and control), with a mean age of 63.7 (SD 10.3) years in the former and 63.3 (SD 9.6) years in the latter. There was a highly significant (p<0.001) elevation in the thymulin levels in POAG patients compared with the control group. However, no significant difference was observed when comparing the plasma NGF levels.Conclusion This is the first report to measure plasma thymulin levels in glaucoma patients. The significant results point the possible role of this immunomodulator in the pathogenesis of primary open angle glaucoma. The potential role of NGF seems to be less likely. These findings warrant further investigation.     

Overexpression of parathyroid hormone-related protein in the skin of transgenic mice interferes with hair follicle development.

Parathyroid hormone-related peptide (PTHrP) was initially discovered as the cause of the syndrome of humoral hypercalcemia of malignancy. Subsequently, the PTHrP gene has been shown to be expressed in a wide variety of normal tissues, including skin. Because the biological function of PTHrP in skin remains unknown, we used the human keratin 14 promoter to target overexpression of PTHrP to the skin of transgenic mice. We achieved a 10-fold level of overexpression in skin, and human keratin 14 promoter-PTHrP transgenic mice displayed a disturbance in normal hair follicle development. These mice either failed to initiate follicle development or showed a delay in the initiation of follicles. These findings suggest that PTHrP normally plays a role in the early stages of hair follicle development and support previous speculation that the peptide may function in regulating cellular differentiation.     

Does chronic prenatal methadone exposure affect beta-receptor subtypes in placental, fetal and maternal brain homogenates?

Computer competition analysis of 3H-DHA (3H-dihydroalprenolol, a nonselective beta-adrenergic radioligand) binding in the presence of unlabeled metoprolol (a beta 1-selective antagonist) indicates the existence of both beta 1- and beta 2-adrenergic receptor subtypes in the rat placenta and confirms previous reports that both beta-adrenoceptors are present in adult rat cortex. In the fetal brain (20th day of gestation), however, only beta 1-receptors were detected. Pregnant rats were chronically exposed to methadone from day 7 to day 20 of gestation via implanted osmotic minipumps (6.3-9.0 mg/kg/day). This treatment schedule did not induce a change in the affinity and density of either beta-receptor subtype in the placental, fetal and maternal brain homogenates. The results are discussed in terms of the reported monoaminergic and opiate receptor functional interactions.     

Extension to the ultrasonic study of supra- and subphrenic spaces of plate-shaped probes initially destined for intracavitary sonography. Research on thoraco-abdominal fluid collections in non-mobilizable patients

The authors describe an original application of real time transducers--initially intended for intracavitary sonography--in thoraco-abdominal scanning. The stic-form probe can be easily slipped under the patient. It is then possible to realize a scan with an upward beam. In the postero-anterior scan, the patient is placed in a supine position. He is motionless. We achieve a better visualization of the liquid collections, since their accumulation is declivious. The method allows a wider sonographic window for thoraco-abdominal and diaphragmatic investigation in sonography.