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Objectives Chronic periodontitis is a common pathological condition that affects the supporting tissue of the teeth, leading to progressive alveolar bone destruction and teeth loss. The disease is caused by bacteria and derives from an altered host immune and inflammatory response, also involving different factors such as the oral hygiene, smoking, and genetic background. The innate immune response, the first line of host defense, could also play an important role in the susceptibility to chronic periodontitis. In this study, we evaluated the possible association between periodontal disease and seven genetic variations within DEFB1 and LTF genes, encoding for β-defensins 1 and lactoferrin (two members of oral innate immune system), in an Italian isolated population. Subjects and Methods DEFB1 5′ UTR g. -52G>A (rs1799946), g. -44C>G (rs1800972), g. -20G>A (rs11362), 3′ UTR c*5G>A (rs1047031), c*87A>G (rs1800971), LTF p.Ala29Thr (rs1126477), and p.Lys47Arg (rs1126478) single nucleotide polymorphisms (SNPs) were analyzed in 155 healthy individuals and 439 chronic periodontitis patients from North-East Italy. Results Significant associations were found between periodontitis and g. -20G>A (rs11362) and g. -44C>G (rs1800972) SNPs in DEFB1 gene as well as p.Ala29Thr (rs1126477) and p.Lys47Arg (rs1126478) SNPs in LTF gene. Discussion Our results suggest the involvement of DEFB1 and LTF genetic variations in the susceptibility toward development of periodontitis. [ABSTRACT FROM AUTHOR]

Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*) heterozygote carrier (n = 11) or not (n = 57). Serum levels of glucose, insulin, and glucagon were measured in a 5 h oral glucose tolerance test using a 75 g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among HTR2B Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the HTR2B Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion. [ABSTRACT FROM AUTHOR]

Aggressive disorders are moderately heritable; therefore, identification of genetic influences is important. The X-linked MAOA gene, encoding the MAOA enzyme, has a functional 30 bp repeat polymorphism in the promoter region ( MAOA-LPR) that has been shown to influence aggression. Childhood trauma is a known risk factor for numerous psychopathologies in adulthood including aggressive behaviors. We investigated the interactive effect of MAOA-LPR genotype and a history of childhood trauma in predicting aggressive behaviors in a prisoner population. A total of 692 male prisoners were genotyped for MAOA-LPR with genotypes grouped into high and low transcriptional activity. Participant evaluations included measures of aggression (Brown-Goodwin Lifetime History of Aggression, BGHA), hostility (Buss-Durkee Hostility Inventory), impulsivity (Barratt Impulsiveness Scale), violence directed toward self and others, and childhood trauma [Childhood Trauma Questionnaire (CTQ)]. MAOA-LPR interacted with CTQ physical neglect (PN), the most common (47%) form of childhood trauma in this sample, to predict BGHA aggression ( P = 0.002). Within the group not exposed to PN, carriers of the MAOA-LPR high-activity variant were more aggressive: ( tR = 2.47, P < 0.014). We observed a crossover effect in that the increase in aggression scores with PN was greater in low-activity individuals ( tR = 5.55, P < 0.0001) than in high-activity individuals ( tR = 4.18, P < 0.0001). These findings suggest that childhood trauma and the functional MAOA-LPR polymorphism may interact to specifically increase risk for over aggressive behavior but not impulsivity or hostility. The MAOA-LPR low-activity variant may be protective against the development of aggressive behavior under low stress conditions, at least in this prisoner population. [ABSTRACT FROM AUTHOR]

Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. It has been suggested that uncoupling protein 3 (UCP3) can increase energy expenditure, thereby regulating body weight. Although studies on UCP3 knock-out mice suggest that lack of UCP3 function does not cause obesity or Type 2 diabetes, it is possible that up-regulation of UCP3 function improves these disorders or their clinical sequelae. A 10- to 20-fold increase of UCP3 gene expression is achievable through physiological or pharmacological stimuli. We examined the phenotype of transgenic mice with approximately 18-fold overexpression of mouse UCP3 mRNA in skeletal muscle. Methods. We generated transgenic mice with approximately 18-fold overexpression of mouse UCP3 mRNA in skeletal muscle under control of the skeletal muscle-specific muscle creatine kinase gene promoter. The phenotype of these mice was analysed either on a standard diet or on a 4-week high-fat diet. Results. In mice on standard chow, there was no difference in body weight, oxygen consumption and mitochondrial protonmotive force between transgenic mice and non-transgenic littermates. However, transgenic mice tended to have lower body weight, increased oxygen consumption and decreased mitochondrial protonmotive force than the control mice. Transgenic mice on a 4-week high-fat diet consumed much more oxygen and had noticeably less weight gain and less epididymal fat, as well as better glucose tolerance than non-transgenic littermates. Conclusions/interpretation. Our study shows that 18-fold overexpression of UCP3 mRNA in the skeletal muscle reduced diet-induced obesity. An 18-fold increase of UCP3 mRNA can be attained by physiological or pharmacological stimuli, suggesting that UCP3 has therapeutic potential in the treatment of obesity. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Forty one moderately impaired patients with clinically confirmed multiple sclerosis (MS) and a relapsing-remitting course were submitted to a neuropsychological battery and magnetic resonance imaging (MRI) to correlate the neuropsychological performances with the degree of cerebral demyelination. The neuropsychological results were indicative of a very mild overall impairment. The patients were subdivided into two groups (extensive periventricular demyelination or discrete lesions on MRI) and the results of neuropsychological tests compared. Patients with extensive periventricular demyelination had an inferior performance on concept formation, non-verbal reasoning and verbal memory tests. [ABSTRACT FROM AUTHOR]

Abnormalities of T-cell subsets in patients with multiple sclerosis are well known; in order to assess whether immunological abnormalities are relevant in the pathogenesis of the disease after its clinical onset, peripheral blood lymphocyte subsets (CD3, CD4, CD4 CD45RA, CD4CD45RA, CD8, CD8CD57, CD57, CD25) were analysed serially in 25 patients at the first clinical episode suggestive of inflammatory demyelinating disease and in an equal number of age- and sex-matched controls. During the follow-up period (12-18 months, mean 14) 6 of 25 patients presented new relapses: in this subgroup of patients, significant changes in CD4 ratio (% CD4CD45RA/%CD4CD45RA) were detected in comparison both with healthy controls and with clinically stable patients. Patients clinically stable at follow-up did not display immunological abnormalities, regardless of the presence or absence of cerebrospinal fluid and/or magnetic resonance imaging alterations consistent with multiple sclerosis. These findings suggest a possible prognostic role of early T-cell subset imbalance in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Nineteen moderately impaired patients with clinically definite multiple sclerosis and an initially relapsing-remitting course were included in a neuropsychological and magnetic resonance imaging (MRI) follow-up study. The average test/re-test interval was about 2 years. The neuropsychological findings were indicative of a very mild overall impairment; the patients, as a group, showed no evidence of cognitive deterioration in the follow-up period. A numerical estimation of the severity of cerebral demyelination shown by MRI did not indicate a significant change. No correlation between cognitive performance variations and MRI changes was found. [ABSTRACT FROM AUTHOR]

Copyright of Giornale Italiano di Medicina del Lavoro ed Ergonomia is the property of Giornale Italiano di Medicina del Lavoro ed Ergonomia Editorial Board and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article examines the genetic aspect of addiction. Addictions are tied together by shared genetic and environmental etiological factors. Craving, binge or intoxication and withdrawal or negative affect are the three phenomena that characterize addiction. It is noted that both genetic and environmental variables contribute to the use of addictive agents and transition from use to addiction. Progress in the pharmacogenetics of addictions would prevent and treat addiction.

The effectiveness of diethylentriamine (DIEN) phosphate buffer at separating basic proteins in bare fused-silica capillaries at various pH values was examined. Such a buffer consists of an aqueous solution of DIEN titrated to the desired pH value with phosphoric acid. The study was conducted by investigating the effect of DIEN phosphate buffer on the electrophoretic mobility and efficiency of four basic proteins at various pH values within the ranges over which the phosphate salts of DIEN are effective at controlling the protonic equilibrium on the basis of the acidic p Ka values of either diethylentriamine or phosphoric acid. The ranges were taken as one pH unit below and above the acidic p Ka values of either DIEN or phosphoric acid. Electrophoretic separations of the four basic proteins performed at the selected pH values, ranging from pH 3.0 to pH 8.0, showed well-resolved efficient and symmetric peaks, demonstrating the capability of DIEN phosphate buffer at inhibiting untoward interactions of basic proteins with the active sites on the inner wall of bare fused-silica capillaries. Such effect is ascribed to the absorption of DIEN ions at the interface between the capillary wall and the electrolyte solution resulting in drastic variations of the positive charge density in the compact region of the electric double layer that, however, are is not suppressing completely the negative charges due to the ionization of silanol groups. Consequently, the net charge within the immobilized region of the electric double layer is negative as evidenced by the cathodic electroosmotic flow measured at any pH value within the range 3.0–8.0, indicative of negative zeta potential. [ABSTRACT FROM AUTHOR]