Thyroid autoimmunity and autoimmune thyroid disease in Malaysian girls with Turner syndrome: An understudied population.

AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls. METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records. RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood. CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

Genetic and metabolic effects of gluconasturtiin, a glucosinolate derived from cruciferae.

It is thought that induction of detoxifying phase-II drug metabolizing enzymes or inhibition of bioactivating phase-I by phytoalexins could protect against mutagens and neoplasia. In the search for potential naturally occurring molecular chemoprevention agents, particular attention has been devoted to isothiocyanates, which are breakdown products-via myrosinase-of glucosinolates such as gluconasturtiin (GNST), a natural constituent of cruciferae. Here, we first investigated the ability of GNST to modulate metabolizing enzymes in male Swiss Albino CD1 mice injected by gavage (24 mg/kg or 48 mg/kg b.w.) with GNST either in single or repeated (daily for four consecutive days) dose. Using selected probes to various cytochrome P450 (CYP) isoforms, a marked and generalized decrease of CYP content, NADPH-(CYP)-c-reductase and various CYP-linked monooxygenases (measuring CYP1A1, CYP2B1/2, CYP3A1/2, CYP1A2 and CYP2E1), was observed in hepatic, renal and pulmonary subcellular preparations (up to approximately 66% loss, liver). Similar behavior was recorded using the regio- and stereo-selective hydroxylation of testosterone as multibiomarker (CYP2A1 and CYP2B9, up to approximately 96% loss), as well as with the phase-II marker glutathione S-transferase (up to approximately 50% loss, liver). We also performed genotoxicity investigations, using the diploid D7 strain of yeast Saccharomyces cerevisiae as a biological test system. GNST was able to significantly induce point reverse mutation in growing cells without myrosinase, thus suggesting either a direct GNST or a CYP-linked metabolite role in the genotoxic response. On the contrary, in suspension test, the addition of myrosinase significantly increased mitotic gene conversion, probably due to the formation of GNST-derived phenylethyl isothiocyanate (PEITC) breakdown product. Taken together, our data suggest that GNST exerts a dual effect: while strongly inhibiting the microsomal (bioactivating) metabolism, GNST also possesses genotoxic activity. This concomitant mutagenic activity underlines the necessity of overall toxicological characterization of this (or any other molecule) prior to mass chemopreventive use.

Protective effect of lipoic acid against hydrogen peroxide in yeast cells.

Lipoic acid (LA) is found in all kinds of cells, it is widely used in medicine and as a dietary supplement, and it is involved in different physiological functions. Even if there are many papers regarding therapeutic effects of LA, medical research does not always support its effectiveness and little is known about LA metabolism in eukaryotic cells. In this work the probable protective effect of LA was investigated employing five strains of yeast Saccharomyces cerevisiae through short term assays. In particular LA behaviour in oxidative stress conditions was studied. For this purpose hydrogen peroxide was used as oxidant. In D7 strain, LA showed antimutagenic effects against hydrogen peroxide and decreased significantly cytochrome P450. To better elucidate the effect of LA the following yeast strains carrying deletions in superoxide dismutase genes (SOD) were employed: EG-103 (wild type), EG-110 strain (without mytochondrial SOD), EG-118 (without cytoplasmatic SOD) and EG-133 (without both enzymes). LA increased the number of mitotic divisions in EG-103, EG-110 and EG-133 and in growing cells (EG-103, EG-110, EG-118) it increased survival percentage with respect to hydrogen peroxide. The positive action was evident in D7 and in EG strains and it showed that LA can be protective and antimutagenic against oxidants in yeast cells, via its antioxidant activity.

[Notes on the use of applied mechanics in a possible interpretation of skull fractures]. / Alcune considerazioni di meccanica applicata per una possibile interpretazione delle fratture craniche.

Principles of applied mechanics dealing with the breakage of two-dimensional medium, flat or round surfaced bodies can be used in the interpretation of skull fractures. Qualitative assessment can be essentially based on Johansen's yielding lines. This offers a justification for the term "lamina vitrea" assigned by anatomists and surgeons to the inner table of the skull.