Plasma oxysterol profiling in children reveals 24-hydroxycholesterol as a potential marker for Autism Spectrum Disorders.

Cholesterol and its oxygenated metabolites, such as oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorder. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, X-linked adrenoleukodystrophy, and Smith-Lemli-Opitz Syndrome. Recent studies have shown that Autism Spectrum Disorders are associated with disruption of cholesterol metabolism. The present study aimed at investigating the profile of oxysterols in plasma and their association with clinical parameters in patients with Autism Spectrum Disorders. Thirty-six children with Autism Spectrum Disorders and thirty-eight healthy children, from Sfax (a southern area of Tunisia) matched for age and sex, were included in the study. The severity of Autism Spectrum Disorders was evaluated using the childhood autism rating scale. Standard lipid profile (total cholesterol, triglycerides, and high-density lipoprotein-cholesterol), serum glucose, high-sensitive C-reactive protein and orosomucoid levels were measured utilizing standard techniques. Oxysterol levels were measured by isotope-dilution gas chromatography/mass spectrometry. Standard lipid profile, serum glucose, high-sensitive C-reactive protein and orosomucoid levels were similar between the two studied populations. Compared to the control group, children with Autism Spectrum Disorders showed a significant higher plasma level of 24-hydroxycholesterol, while borderline significance was observed for 7α-hydroxycholesterol, and 25-hydroxycholersterol. In patients, 24-hydroxycholesterol was inversely correlated with age. Multivariate analysis showed that high plasma levels of 24-hydroxycholesterol are independent risk factors for Autism Spectrum Disorders. On the other hand, an analysis of the receiver's operating characteristics proved that the measured parameters recorded satisfactory levels of specificity and sensitivity. The present study provides evidence that Autism Spectrum Disorders are associated with altered levels in circulating oxysterols. The finding that 24-hydroxycholesterol is an independent risk factor for the disease and suggests the use of this oxysterol as a diagnostic tool in Autism Spectrum Disorders.

[TAFRO syndrome and monoclonal gammapathy: Uncommon association!]. / Syndrome de TAFRO et gammapathie monoclonale : association inhabituelle !

Castleman's disease is a lymphoproliferative disorder characterized by angiofollicular lymph node hyperplasia. Recently, a new variant of multicentric Castleman's disease has been identified in Japan called TAFRO syndrome. It is characterized by a constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction and organomegaly (TAFRO). It is usually associated with polyclonal hyperimmunoglobulinemia. Here, we report the first and unique case of TAFRO syndrome with monoclonal gammapathy.

Male hypogonadism and metabolic syndrome.

The role of androgens in cardiovascular disease is still controversial in men. In this study, we investigated metabolic disorders in Tunisian hypogonadal men compared with healthy controls. Forty hypogonadal men and 80 control subjects were enrolled. Patients with a history of pre-existing panhypopituitarism, thyroid dysfunction or inflammatory disease were excluded. Glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein (hsCRP), lipid profile, insulin, testosterone and gonadotrophins were measured. Insulin resistance was assessed by homoeostasis model assessment of insulin resistance (Homa IR). Waist circumference, body mass index and blood pressure were significantly higher in patients compared with controls. Glycemia, HbA1c, fasting serum insulin and Homa IR were significantly increased among hypogonadal men. In univariate analysis, testosterone levels were inversely correlated with body mass index, waist circumference, blood pressure, glycaemia, HbA1C, insulin, Homa IR and hsCRP. In multivariate analysis including all significant variables, initial testosterone level was the only independent risk factor for developing dyslipidaemia. With logistic regression, male hypogonadism was an independent risk factor for MS (P < 0.001). We conclude that low testosterone level plays a central role in the development of metabolic syndrome. Further prospective data are required to establish the causative link.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and variations of homocysteine concentrations in patients with Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a chronic, relapsing, multi-systemic inflammatory disorder of unknown causes. This disease is mainly characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The aim of this study is to investigate the associations between C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the plasma homocysteine (Hcy), folate, and B12 levels in a relatively large cohort of Tunisian patients with BD. METHODS: The study included 142 patients with BD and 172 healthy controls. The C677T and A1298C polymorphisms were genotyped using PCR-RFLP. Serum Hcy level was determined using a fluorescence polarization immunoassay. Serum folate and vitamin B12 levels were measured by electrochemiluminescence immunoassay. RESULTS: Genotype and allele frequencies of the two studied MTHFR polymorphisms did not show any significant differences among BD patients compared to controls. Patient carriers of the 677TT variant and the 677T allele displayed significantly higher Hcy concentration. Moreover, no significant association was found between neither A1298C polymorphism nor the C allele and Hcy, folate, and B12 levels. In multivariate analyses, we reported that 677T allele, male gender, and creatinine level were independent risk factors for hyperhomocysteinemia (HHC). CONCLUSIONS: In the present study, we report the absence of any significant differences between genotype and allele frequencies for both studied polymorphisms among BD patients compared to healthy controls. Besides, we showed that the T allele of MTHFR C677T polymorphism influenced the Hcy level which is an independent risk factor for HHC in Tunisian BD patients.

Rapid compensation of horizontal optokinetic nystagmus in hemilabyrinthectomized rats: a fast return to symmetry.

In the rat, after unilateral labyrinthectomy the loss of unit responses in the deafferented ipsilateral vestibular nucleus should lead to a complete postlesional asymmetry in H-OKN. The compensation process of this oculomotor deficit were recorded by means of a search coli technique using amplitude detection in 30 pigmented rats, 8 animals as control and 22 submitted to left hemilabyrinthectomy. Recording sessions were performed from day 1 to 8 after the lesion. Velocity steps of visual stimulation were delivered in clockwise (CW) and counterclockwise (CCW) directions at velocities from 2 to 40 degrees/s. The H-OKN was not observable on postlesional day 2. It reappeared asymmetrical on day 2 with depressed responses to CW stimulation while the response to the CCW stimulation were almost as large as in intact animal. This asymmetry was quantified by the gain values (eye velocity/stimulus velocity) of the nystagmic responses which were, at 5 degrees/s of stimulus velocity, 0.37 for CW stimulation and almost twice as large, 0.72 for CCW stimulation. Later this asymmetry was consistently reduced by a progressive increase of the CW responses and a parallel decrease of the CCW. This process led to the responses to reach almost symmetrical values on day 8 with a gain of 0.52 and 0.63 for CW and CCW responses respectively at the same stimulus velocity. However the gain of intact animals was never attained. The initial eye velocity was symmetrically altered on day 2 and remained unchanged until postlesional day 8. These results demonstrate that the deficit appeared to be compensated more by a restoration of a symmetry than by a restitution of a gain of responses equivalent to that of an intact animal.