Arterial spin-labeling magnetic resonance imaging of brain maturation in early childhood: Mathematical model fitting to assess age-dependent change of cerebral blood flow.

PURPOSE: To determine the trajectory of age-dependent cerebral blood flow (CBF) change in infants and young children by fitting mathematical models to the imaging data. METHODS: In this retrospective study, we reviewed the arterial spin-labeling imaging studies of 49 typically developing infants and young children at postmenstrual age (PMA) ranging from 38 to 194 weeks. All patients had normal structural MR imaging. Coregistration and gray matter segmentation were performed to extract whole-brain CBF values. Regional CBF values were obtained using manual region-of-interest placement. Curve estimation regression procedures with the corrected Akaike information criterion (AICc) were performed to determine the mathematical model best fitting the relationship between the CBF (whole-brain and regional measurements) and PMA of the patients. RESULTS: Whole-brain CBF trajectory was best fitted by a cubic model (AICc = 215.95; R2 = 0.566; P < .001). Whole-brain CBF at 1, 6, 12, and 24 months was estimated to be 36, 52, 58, and 55 mL/100 g/min, respectively. Regional CBF trajectory was also best fitted by a cubic model in the frontal (AICc = 233.63; R2 = 0.442; P < .001), parietal (AICc = 229.18; R2 = 0.614; P < .001), basal ganglion (AICc = 239.39; R2 = 0.178; P = .043), temporal (AICc = 236.01; R2 = 0.441; P < .001), and occipital (AICc = 236.46; R2 = 0.475; P < .001) regions. CONCLUSIONS: In early childhood, the trajectory of CBF change was nonlinear and best fitted by the cubic model for the whole brain and all brain regions.

Tract-based spatial statistics: application to mild cognitive impairment.

RATIONALE AND OBJECTIVES: The primary objective of the current investigation was to characterize white matter integrity in different subtypes of mild cognitive impairment (MCI) using tract-based spatial statistics of diffusion tensor imaging. MATERIALS AND METHODS: The study participants were divided into 4 groups of 30 subjects each as follows: cognitively healthy controls, amnestic MCI, dysexecutive MCI, and Alzheimer's disease (AD). All subjects underwent a comprehensive neuropsychological assessment, apolipoprotein E genotyping, and 3-tesla MRI. The diffusion tensor was reconstructed and then analyzed using tract-based spatial statistics. The changes in brain white matter tracts were also examined according to the apolipoprotein E ε 4 status. RESULTS: Compared with controls, amnestic MCI patients showed significant differences in the cerebral white matter, where changes were consistently detectable in the frontal and parietal lobes. We found a moderate impact of the apolipoprotein E ε 4 status on the extent of white matter disruption in the amnestic MCI group. Patients with AD exhibited similar but more extensive alterations, while no significant changes were observed in dysexecutive MCI patients. CONCLUSION: The results from this study indicate that amnestic MCI is the most likely precursor to AD as both conditions share significant white matter damage. By contrast, dysexecutive MCI seems to be characterized by a distinct pathogenesis.

Sex dimorphism of cortical water diffusion in normal aging measured by magnetic resonance imaging.

BACKGROUND: The purpose of this study was to examine sex dimorphism in water diffusion in the brain throughout the normal aging process by magnetic resonance imaging. METHODS: Diffusion-weighted images covering the majority of the brain were acquired from 77 healthy participants. Both the mean water diffusivity and diffusion kurtosis were calculated from the cortical regions and parcellated according to the template in anatomical automatic labeling. The mean water diffusivity and diffusion kurtosis from both sexes were examined and subsequently correlated with age. Statistical significance was set at a threshold of p < 0.01 after correction for multiple comparisons. In regions that reached statistical significance, a linear regression model was performed. Analysis of variance was conducted to determine the interaction between aging and sex. RESULTS: Sex differences were observed for three aspects. First, compared to females, males presented increased mean water diffusivity and a decreased diffusion kurtosis in the frontal and temporal lobes. Second, a widespread age-related increase in mean water diffusivity was observed, which was more significant in the frontal, occipital, and temporal areas and in the cingulum in females. Third, the diffusion kurtosis decreased with aging but only in restricted areas for both sexes. For the interaction of aging and sex, the most significant change was observed with regards to mean diffusivity, mostly in the right amygdala. CONCLUSIONS: A sex-related dimorphism in water diffusion throughout the aging process was observed in the cortex using magnetic resonance imaging.

Plasma klotho levels decrease in both anorexia nervosa and obesity.

OBJECTIVE: The aim of this study was to examine the associations of klotho with body mass index (BMI) in patients with restricting-type anorexia nervosa (r-AN) and obesity. METHOD: We examined plasma klotho as well as adiponectin and its isoform levels in comparison in 11 obese patients, 12 r-AN patients, and 11 control participants. RESULTS: Plasma klotho levels were markedly lower in the obesity and r-AN groups than in the control group. Moreover, plasma klotho levels increased significantly after the recovery of BMI in r-AN patients. Total and high-molecular-weight adiponectin levels were significantly decreased only in obesity. There was no relationship between klotho and total adiponectin levels or klotho and respective adiponectin isoform levels in the entire study population. CONCLUSIONS: These results suggest that klotho may reflect normal nutritional state, and that the decrease of klotho in r-AN and obesity may underlie the deteriorating processes of these disorders.

Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.

Hydrogen (H(2)) acts as a therapeutic antioxidant. However, there are few reports on H(2) function in other capacities in diabetes mellitus (DM). Therefore, in this study, we investigated the role of H(2) in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2) promoted 2-[(14)C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2) significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p.) and oral (p.o.) administration. However, long-term p.o. administration of H(2) had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2) exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

A case of anorexia nervosa with disseminated intravascular coagulation syndrome.

A 36-year-old Japanese woman with anorexia nervosa (AN) was admitted to our department because of severe emaciation. Although we were thorough in her clinical management and were careful to avoid precipitating refeeding syndrome, disseminated intravascular coagulation (DIC) developed 3 weeks after hospitalization. We treated her for DIC with sepsis using anticoagulants, protease inhibitors, antithrombin, and platelet concentrate transfusion. To treat her bacterial infection, we administered antimicrobial drugs and immunoglobulin. We began probiotic and prebiotic (synbiotics) treatment for bacterial translocation. We think that the prevention of sepsis via bacterial translocation is an important aspect of care for patients with severe AN in addition to the prevention of refeeding syndrome.

Stimulation of leptin secretion by insulin.

Leptin has a crucial role in regulating food intake and maintaining metabolic homeostasis. Although little is known about the process of leptin secretion, insulin, which has an important role in the metabolism of glucose and lipids, is believed to regulate leptin secretion through a posttranscriptional mechanism in the short term, and via glucose metabolism in the long term. The gastric mucosa secretes leptin, but this mechanism has not been completely elucidated. Understanding the mechanism of insulin-regulated leptin secretion could lead to the development of new treatment methods for obesity and its comorbidities, which are serious public health concerns.

Zinc as an appetite stimulator - the possible role of zinc in the progression of diseases such as cachexia and sarcopenia.

Zinc is required by humans and animals for many physiological functions, such as growth, immune function, and reproduction. Zinc deficiency induces a number of physiological problems, including anorexia, growth retardation, dermatitis, taste disorder, and hypogonadism. Although it is clear that zinc deficiency produces specific and profound anorexia in experimental animals, the connection between zinc deficiency and anorexia is less certain. We were the first to show that orally, but not intraperitoneally, administered zinc rapidly stimulates food intake through orexigenic peptides coupled to the afferent vagus nerve using rats during early-stage zinc deficiency without decreased zinc concentrations in plasma and tissues. We confirmed that a zinc-sufficient diet containing zinc chloride acutely stimulated food intake after short-term zinc deprivation. We also found that orally administered zinc sulfate increased the expression of NPY and orexin mRNA after administration. Using vagotomized rats, we tested whether the increase in food intake after oral administration of zinc was mediated by the vagus nerve. In sham-operated rats, the oral administration of zinc stimulated food intake, whereas zinc and saline administrations did not exhibit differing effects in vagotomized rats. We conclude that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve with subsequent effects on hypothalamic peptides associated with food intake regulation. In this review, we describe recent research investigating the roles of zinc as an appetite stimulator in food intake regulation, along with research about hypothalamus, ghrelin, leptin and zinc receptor, and clinical application about anorexia nervosa, cachexia and sarcopenia. The article also presents some promising patents on zinc.

Biological effects of obestatin.

Obestatin, a 23-amino-acid peptide, is derived from the preproghrelin precursor. Obestatin was identified in 2005 as a hormone regulating food intake and energy, and having opposite effects to those of ghrelin. However, as studies have progressed, many disputes on the physiological function of obestatin have emerged. The food intake suppressive effects of obestatin have not been replicated in many studies. Nonetheless, many biological roles of obestatin have been revealed, and obestatin is thought to be associated with a variety of biological functions such as feeding, drinking, incretion, memory, and sleep, and with neuropsychiatric manifestations. The biological effects of obestatin will be reviewed in this article.

Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in mice.

Lifestyle-related diseases are associated with overeating and lack of exercise. The purpose of this study was to investigate the effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels. Mice were housed for 4 weeks in 4 groups, which included the non-exercise and normal diet (SN), exercise and normal diet (EN), non-exercise and high-fat diet (SF) and the exercise and high-fat diet (EF) group. The mice in the exercise groups were housed in cages with a running wheel and were subjected to voluntary exercise. The food intake (Kcal) of the mice in the exercise groups increased compared to that of the mice in the non-exercise groups (P<0.01). Body weight and visceral fat decreased in the mice in the EF group compared to the mice in the SF group (P<0.01 and P<0.05). The temperature of the mice in the EF group increased compared to that of the mice in the SN group (P<0.05). Blood glucose, insulin (P<0.01), cholesterol (P<0.01) and triglyceride concentrations (P<0.01) increased in the SF group compared to the normal diet groups. Furthermore, plasma insulin and cholesterol concentrations increased in the SF group compared to the exercise groups (P<0.01). Plasma adiponectin and nesfatin-1 levels in the SF group decreased compared to the SN group (P<0.05). Exercise under a high-fat diet antagonized the significant decrease in the nesfatin-1 level. Exercise together with a high-fat diet affected the plasma levels of adiponectin and nesfatin. It is therefore suggested that exercise together with a high-fat diet can affect various diseases via adiponectin and nesfatin.

The role of CRF family peptides in the regulation of food intake and anxiety-like behavior.

Corticotropin-releasing factor (CRF) and the urocortins (UCN1, UCN2, and UCN3) belong to the CRF family of peptides and are the major regulators of the adaptive response to internal and external stresses. The actions of CRF and UCNs are mediated through two receptor subtypes: CRF receptor 1 (CRFR1) and CRFR2. Their physiological roles, among other functions, include the regulation of food intake and anxiety-like behavior. In this review, we describe the progress that has been made towards understanding how anxiety- and depression-like behavior and food intake are regulated by CRF, UCN1, UCN2, and UCN3.

Centrally administered nesfatin-1 inhibits feeding behaviour and gastroduodenal motility in mice.

Nesfatin-1 was recently identified as a peptide with anorexigenic effects that is localized in the hypothalamus and adipocytes. Not much is known about the effect of nesfatin-1 on gut motility. Food intake was measured after intracerebroventricular administration of nesfatin-1 in food-deprived mice. Antral and duodenal motility was assessed by using a manometric method in conscious fed mice. We found that centrally administered nesfatin-1 decreased food intake and inhibited gastroduodenal motility in mice. These results suggest that nesfatin-1 influences gut motility and feeding behaviour.