High performance liquid chromatography of long-chain acylcarnitine and phospholipids in fatty acid turnover studies.

In this paper we describe a rapid, isocratic high performance liquid chromatography (HPLC) method for the study of radioactive fatty acid incorporation into complex lipids of human erythrocytes, which allows the simultaneous separation of the major phospholipid classes and long-chain acylcarnitines. The lipid extract of erythrocytes pulsed with radioactive fatty acids was injected into an HPLC system equipped with a silica column. The individual components eluted were monitored by ultraviolet absorption and radioactive emission. With respect to the UV profile, the radioactive profile showed an additional peak between phosphatidyl-choline and phosphatidylethanolamine, which was identified as long-chain acylcarnitine by different experimental approaches. The radioactivity recovered in the long-chain acylcarnitines contains essential information enabling definition of acyl trafficking in red cells

Acute Disseminated Encephalomyelitis followed by Optic Neuritis: A Rare Syndrome of Uncertain Treatment and Prognosis

Aim Acute Disseminated Encephalomyelitis followed by optic neuritis (ADEM-ON), first described in 2013, is a rare demyelinating syndrome, typical of the pediatric age. We conducted a mini review of the existing literature, focusing on clinical, laboratory, radiological, therapeutic, and prognostic aspects in order to improve the identification of new cases. Methods We searched PubMed and Cochrane Library for studies on ADEM-ON between 2013 and 2018. Results Examination of the reported cases (three case reports and eight observational studies) established the following features. Time between ADEM and ON is highly variable. Almost all patients show antimyelin oligodendrocyte glycoprotein antibody (MOG-abs) seropositivity. High-dose intravenous steroid and plasmapheresis efficacy is reported for the acute phase; oral prednisone and other maintenance drugs may be useful in avoiding relapses. The clinical history may lead to a complete recovery but also to residual deficits. Conclusion MOG-abs detection strongly supports ADEM-ON diagnosis, confirming this entity as part of MOG-abs spectrum disorder. Owing to the very small number of cases so far reported, predicting clinical evolution is very difficult

DRD1 and DRD2 Receptor Polymorphisms: Genetic Neuromodulation of the Dopaminergic System as a Risk Factor for ASD, ADHD and ASD/ADHD Overlap

The dopaminergic system (DS) is one of the most important neuromodulator systems involved in complex functions that are compromised in both autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), conditions that frequently occur in overlap. This evidence suggests that both disorders might have common neurobiological pathways involving the DS. Therefore, the aim of this study was to examine the DRD1 and DRD2 dopamine receptor single nucleotide polymorphisms (SNPs) as potential risk factors for ASD, ADHD, and ASD/ADHD overlap. Genetic data were obtained from four groups: 75 ASD patients, 75 ADHD patients, 30 patients with ASD/ADHD overlap, and 75 healthy controls. All participants were between 2 and 17 years old. We compared the genotypic and allelic frequency of 18 SNPs among all of the study groups. Moreover, in the case of statistically significant differences, odds ratios (OR) were obtained to evaluate if the presence of SNPs might be a risk factor of developing a specific clinical phenotype. This study found that DRD1 and DRD2 receptors SNPs might be considered as potential risk factors for ASD and ADHD. However, only DRD2-12 (rs7131465) was significantly associated with a higher risk for the ASD/ADHD overlap. These data support the hypothesis of the genetic neuromodulation of the DS in the neurobiology of these conditions

14q12q13.2 microdeletion syndrome: Clinical characterization of a new patient, review of the literature, and further evidence of a candidate region for CNS anomalies

Background: Chromosome 14q11-q22 deletion syndrome (OMIM 613457) is a rare contiguous gene syndrome. Two regions of overlap (RO) of the 14q12q21.1 deletion have been identified: a proximal region (RO1), including FOXG1(*164874), NKX2-1(*600635), and PAX9(*167416) and a distal region (RO2), including NKX2-1 and PAX9. We report a 6-year-old boy with mild dysmorphic facial features, global developmental delay, and hypoplasia of the corpus callosum. Methods and Results: Array-CGH analysis revealed a 14q12q13.2 microdeletion. We compared the phenotype of our patient with previously published cases in order to establish a genotype–phenotype correlation. Conclusion: The study hypothesizes the presence of a new RO, not including the previously reported candidate genes, and attempt to define the associated molecular and psychomotor/neurobehavioral phenotype. This region encompasses the distal breakpoint of RO1 and the proximal breakpoint of RO2, and seems to be associated with intellectual disability (ID), hypotonia, epilepsy, and corpus callosum abnormalities. Although more cases are needed, we speculated on SNX6(*606098) and BAZ1A(*605680) as potential candidate genes associated with the corpus callosum abnormalities

Human adipose tissue stem cells: relevance in the pathophysiology of obesity and metabolic diseases and therapeutic applications.

Stem cells are unique cells exhibiting self-renewing properties and the potential to differentiate into multiple specialised cell types. Totipotent or pluripotent stem cells are generally abundant in embryonic or fetal tissues, but the use of discarded embryos as sources of these cells raises challenging ethical problems. Adult stem cells can also differentiate into a wide variety of cell types. In particular, adult adipose tissue contains a pool of abundant and accessible multipotent stem cells, designated as adipose-derived stem cells (ASCs), that are able to replicate as undifferentiated cells, to develop as mature adipocytes and to differentiate into multiple other cell types along the mesenchymal lineage, including chondrocytes, myocytes and osteocytes, and also into cells of endodermal and neuroectodermal origin, including beta-cells and neurons, respectively. An impairment in the differentiation potential and biological functions of ASCs may contribute to the development of obesity and related comorbidities. In this review, we summarise different aspects of the ASCs with special reference to the isolation and characterisation of these cell populations, their relation to the biochemical features of the adipose tissue depot of origin and to the metabolic characteristics of the donor subject and discuss some prospective therapeutic applications

Hyperprolactinemia and insulin resistance in drug naive patients with early onset first episode psychosis

Abstract Background Hyperprolactinemia and glucose and lipid metabolism abnormalities are often found in patients with schizophrenia and are generally considered secondary to the use of antipsychotic drugs. More recent studies have shown these same neuroendocrine and metabolic abnormalities in antipsychotic naïve patients with first episode psychosis (FEP), rising the hypothesis that schizophrenia itself may be related to an abnormal regulation of prolactin secretion and to impaired glucose tolerance. The aim of this study was to compare prolactin levels, glycometabolism parameters and lipid profile between a sample of 31 drug-naive adolescents in the acute phase of FEP and a control group of 23 subjects at clinical high risk (CHR) of developing psychosis. Methods The assessment involved anthropometric data (weight, height, BMI index, pubertal stage) and blood tests (levels of glucose, glycated hemoglobin, serum insulin, triglycerides, total and fractionated cholesterol, prolactin). Insulin resistance (IR) was calculated through the homeostatic model of assessment (HOMA-IR), assuming a cut-off point of 3.16 for adolescent population. FEP patients and CHR controls were compared by using Student’s t-distribution (t-test) for parametric data. P < 0.05 was considered significant. Results Significant higher level of prolactin was found in FEP group than in CHR group (mean = 28.93 ± 27.16 vs 14.29 ± 7.86, P = 0.009), suggesting a condition of hyperprolactinemia (HPRL). Patients with FEP were more insulin resistant compared to patients at CHR, as assessed by HOMA-IR (mean = 3.07 ± 1.76 vs 2.11 ± 1.11, P = 0.043). Differences of fasting glucose (FEP = 4.82 ± 0.71, CHR = 4.35 ± 0.62, P = 0.016) and HbA1c (FEP = 25.86 ± 13.31, CHR = 33.00 ± 2.95, P = 0.013), were not clinically significant as the mean values were within normal range for both groups. No significant differences were found for lipid profile. A BMI value within the range of normal weight was found for both groups, with no significant differences. Conclusion We suggested that HPRL, increase in HOMA-IR, and psychotic symptoms may be considered different manifestations of the acute onset of schizophrenia spectrum psychosis, with a common neurobiological vulnerability emerging since adolescence. The influence of age and gender on clinical manifestations of psychotic onset should be considered for early prevention and treatment of both schizophrenia spectrum psychosis and neuroendocrine-metabolic dysfunctions