In silico identification of new candidate genes for hereditary congenital facial paresis

Hereditary congenital facial paresis (HCFP) consists of the paralysis or weakness of facial muscles caused by a maldevelopment of the facial branchiomotor (FBM) nucleus and its nerve. Linkage analyses have related this disorder to two loci, HCFP1 and HCFP2, placed respectively in human chromosomes 3q21.2-q22.1 and 10q21.3-q22.1, but the causative genes are still unknown. In this work we aimed to identify which genes from these loci are expressed in the developing hindbrain and particularly in the FBM nucleus. To this end, we retrieved from the ENSEMBL genomic database the list of these genes as well as their respective mouse orthologs. Subsequently we examined their respective expression patterns in the mouse embryo by using the GenePaint gene expression database. As a result of this screening, we found a new gene (Mgll) from the HCFP1 locus that has strong and specific expression in the developing FBM nucleus. In its turn, the HCFP2 locus appeared as a large gene-desert region, flanked by two genes, Reep3, with specific expression in the FBM nucleus, and Lrrtm3, broadly expressed in the brainstem, including the same nucleus. The concurrence of genomic position and neural expression pattern makes these genes new potential candidates for HCFP.     

Glucosamine attenuates increases of intraabdominal fat,serum leptin levels,and insulin resistance induced by a high-fat diet in rats

The levels of circulating nonesterified fatty acids increase during obesity and contribute to insulin resistance by inhibiting insulin-stimulated glucose transport and phosphorylation in human muscles. In cells, glucose-6-phosphate is primarily used in glycogenesis and glycolysis; only 1% to 3% is converted to glucosamine-6-phosphate, which enters the hexosamine-biosynthesis pathway. The major end product of this pathway, uridine-5′-diphosphate-N-acetyl-glucosamine, which is increased by exogenous glucosamine (GlcN) administration, mediates insulin resistance. We hypothesized that the administration of GlcN to rats receiving a high-fat (HF) diet may potentiate the effects of an HF diet on glucose tolerance and other metabolic variables. To evaluate this relationship, 2 groups of rats were fed with a control or HF diet; and another 2 groups received glucosamine hydrochloride at a dose of 500 mg/kg dissolved in drinking water for 21 weeks. Metabolic variables related to insulin resistance were then measured. The levels of blood glucose and serum insulin were higher in a glucose tolerance test in the HF group as compared with the control group. Rats receiving GlcN had reduced liver glycogen and only slightly worsened glucose tolerance as compared with control rats, although this did not induce insulin resistance as evaluated by the homeostasis model assessment. Glucosamine administration was able to partially or completely inhibit some effects of the HF diet by reducing fat depot weight and serum leptin levels, thus resulting in a smaller increase in the insulinemic response to a glucose injection and lower postabsorptive glycemia.     

Iron supplementation decreases plasma zinc but has no effect on plasma fatty acids in non-anemic women

Limited information is available on the role of iron in fatty acid metabolism in humans. We hypothesized that iron supplementation will increase desaturase activity, and so, the aim of this study was to determine the effect of iron supplementation on fatty acid desaturase activity in young women. Participants were randomly assigned to a control group (CG) or supplementation group (SG) who were provided with 37.4 mg of elemental iron daily for 12 weeks. Forty women completed the trial, n = 19 in CG and n = 21 in SG. The mean ages were 25.2 and 24.6 years, and body mass indices were 21.8 and 21.2 (kg/m²) in CG and SG, respectively. Serum ferritin concentrations increased significantly (P < .01) in subjects assigned to SG but were unchanged in CG. Serum iron concentrations were not significantly changed. Plasma zinc concentrations at the end of the intervention were similar to baseline values for individuals in CG but were decreased significantly (P = .004) in SG. Plasma fatty acids, phospholipid fatty acids, and desaturase activities, expressed as precursor-to-product ratios, were not significantly affected by the intervention, although in SG the concentration of serum ferritin was correlated positively (P < .05) with Δ6-desaturase activity. Supplementing non-anemic women with low dose iron improves iron status but has no significant effect on desaturase activity. The lack of a clear effect on an indirect indicator of desaturase activity may be related to the antagonism between iron and zinc, as illustrated by the decrease in plasma zinc concentrations in women who were supplemented with iron.     

Wideband reflectance in Down syndrome

ObjectiveChildren with Down syndrome (DS) have a high incidence of middle ear disorders and congenital abnormalities of the external, middle and inner ear. Energy reflectance (ER), a wideband acoustic immittance (WAI) measurement parameter, can measure the sound energy reflected or absorbed in the ear canal over a wider range of frequencies more efficiently and faster than conventional single-tone 226 Hz tympanometry. The aim of the present study was to compare the WAI measurements of children with DS with those of typically developing, normal-hearing children according to their tympanometric findings.MethodsFour groups of children with Down syndrome (age range: 2 years and 4 months to 16 years and 3 months; mean age: 8.5 yr) with normal tympanograms (19 ears), flat tympanograms (13 ears), mild negative pressure tympanograms (6 ears between −100 and −199 daPa at the admittance peak) and severe negative pressure tympanograms (4 ears at −200 daPa or lower at the admittance peak) were assessed. All findings were compared with data obtained from 21 ears of a healthy control group (age range: 3 years and 1 month to 13 years and 11 months; mean age: 7.9 yr). The subjects underwent tympanometry with a 226-Hz probe tone frequency and ER measurements along the 200–6,000 Hz range with a chirp stimulus using the Middle-Ear Power Analyzer (MEPA3 – HearID) by Mimosa Acoustics (Champaign, IL), software, version 3.3 [38].ResultsStatistically significant differences were observed in the ER curves for some comparisons between the studied groups. There was also a negative correlation between the static acoustic admittance at the tympanic membrane level and ER measured with a chirp stimulus at 500 and 1,000 Hz. The discriminant analysis technique, which used a chirp stimulus at 1,000 and 1,600 Hz to classify the participants' data based on ER values, achieved a correct classification rate of 59.52% for participants with DS.ConclusionWhile groups with abnormal middle ear status, as indicated by tympanometry, showed higher ER values compared to the DS tymp A group and the control group, similar reflectance curves were observed between control group and the DS tymp A group. WAI shows promise as a clinical diagnostic tool in investigating the impact of middle ear disorders in DS group. However, further research is required to investigate this issue in narrower age range group and a larger sample size.     

Human safety study of body lotion containing Kathon® CG

The safety of Kathon CG biocide as a preservative in leave-on body lotions was assessed by 2 double-blind studies, using similar protocols. A total of 209 healthy male and female subjects aged 18 to 65 years, 100 in California (72 test subjects, 28 controls) and 109 in Florida (88 test subjects, 21 controls) completed the studies which included pre- and post-use phase diagnostic patch testing with Kathon CG 100 ppm active ingredient, and 13 weeks daily applications of either a test lotion containing Kathon CG 15 ppm active ingredient or a control lotion without Kathon CG. No evidence of irritation or sensitization attributable to use of the biocide was found during regular dermatological examinations during the use phase. Post-use phase patch testing produced negative results in all subjects with the exception of 1 control subject in Florida who had positive readings at the 2- and 4-week post-use phase patch testing. Overall, these studies show there is minimal, if any, risk of adverse effects associated with the use of Kathon CG 15 ppm active ingredient in a leave-on application.     

Sensitization to Kathon CG in Geneva and Switzerland

Between October 1986 and June 1987 we patch tested 420 patients with Kathon CG at 100 ppm and obtained 23 positive reactions (5.5%). The other 5 Swiss university clinics joined our study between January and June 1987 and obtained sensitization rates ranging from 0.7 to 7.5%. The total mean value including Geneva was 3.6%. We did threshold patch testing in 12 patients with the following Kathon CG dilutions: 100, 50, 25, 15 and 7 ppm. We observed progressively diminishing skin reactions, especially below 25 ppm, but we still obtained slight positive reactions in 2 patients with Kathon CG at 7 ppm. Those reactions were relevant because the dermatitis disappeared when the use of Kathon-containing creams was discontinued.     

Frequency of sensitisation to the preservative Kathon® CG

The incidences of sensitisation to Kathon CG are reported for patients routinely tested from 1984 to 1986 in Bari, London, Louvain, Nijmegen, Oulu and San Francisco. For these 3 years, the overall frequency of sensitisation varied for women from 3.3% in Oulu to 0.6% in London and San Francisco and for men from 1.4% in Oulu to 0% in San Francisco. Women were predominantly sensitised, probably by cosmetics, toiletries and domestic cleaners. Occupational sensitisation was much less frequent.