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Biomedical subjects

Nobuo Kiriike

Publications and source records attributed to Nobuo Kiriike.

At least 19 recordsLinked to original sources

Corticotropin-releasing factor receptor type 1, but not type 2, in the ventromedial hypothalamus modulates dopamine release in female rats.

Corticotropin-releasing factor (CRF) plays an important role in stress responses and is mediated through two subtypes of receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Each CRF receptor might have a different function through several neurotransmitter systems; however, the mechanism remains unclear. To clarify the role of each receptor in dopamine (DA) metabolism, we measured the change of extracellular concentrations of DA and the metabolites in the ventromedial hypothalamus (VMH) that played important roles in the stress response of freely moving female rats in response to the direct administration of comparative CRFR1 selective agonist, CRF, or CRFR2 selective agonist, Urocortin II (Ucn II), into the brain region. Administration of 10 microg CRF increased extracellular concentrations of DA compared with 2 microg CRF immediately after injection, and this effect was not observed after 60 min of 10 microg CRF injection. On the other hand, this change did not always occur after Ucn II administration. These results suggest that the activation of CRFR1, but not CRFR2, modulates the release of DA in VMH.

3,4-Dihydroxyphenylacetic Acid↗

An open trial of paroxetine for the "offensive subtype" of taijin kyofusho and social anxiety disorder.

The taijin kyofusho (TKS) offensive subtype is thought to be a culture-bound syndrome similar to social anxiety disorder (SAD). In Western countries, such patients would be diagnosed as having delusional disorder, somatic subtype, or body dysmorphic disorder. Recently, open trials for the TKS offensive subtype and a randomized controlled trial for body dysmorphic disorder demonstrated that selective serotonin reuptake inhibitors (SSRIs) might be as effective in TKS as in SAD. This study investigated the efficacy of the SSRI paroxetine in patients with the TKS offensive subtype, both on anxiety and fears, as well as insight. This study was a 12-week open trial using paroxetine in 22 patients with TKS. Subjects were diagnosed based on the original diagnostic criteria for the TKS offensive subtype. Insight regarding TKS symptoms was assessed by the 11th supplement subscale "Insight into obsessions and compulsions" of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The Liebowitz Social Anxiety Scale (LSAS), the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), Rosenberg's Self-Esteem Scale, and the Interpersonal Distrust subscale of the Eating Disorder Inventory were also administered. Offensive anxiety was assessed by the original TKS offensive anxiety subscale (0-3 points). The primary efficacy variable was the Clinical Global Impression scale (CGI) global improvement item. Nineteen patients completed the study. Forty-seven percent (9/19) were responders to the drug treatment (scoring 2 or less on the CGI). Last observation carried forward (LOCF) analysis (N=22) demonstrated a statistically significant reduction in LSAS total score and offensive anxiety in TKS, and the insight scale score of the Y-BOCS also significantly improved. Interpersonal distrust showed a trend toward improvement.

Adult↗

Anxiety-induced plasma norepinephrine augmentation increases reactive oxygen species formation by monocytes in essential hypertension.

BACKGROUND: An association between anxiety and depression and increased blood pressure (BP) and cardiovascular disease risk has not been firmly established. We examined the hypothesis that anxiety and depression lead to increased plasma catecholamines and to production of reactive oxygen species (ROS) by mononuclear cells (MNC) in hypertensive individuals. We also studied the role of BP in this effect. METHODS: In Protocol 1, a cross-sectional study was performed in 146 hypertensive patients to evaluate whether anxiety and depression affect BP and ROS formation by MNC through increasing plasma catecholamines. In Protocol 2, a 6-month randomized controlled trial using a subtherapeutic dose of the alpha(1)-adrenergic receptor antagonist doxazosin (1 mg/day) versus placebo in 86 patients with essential hypertension was performed to determine whether the increase in ROS formation by MNC was independent of BP. RESULTS: In Protocol 1, a significant relationship was observed between the following: trait anxiety and plasma norepinephrine (r = 0.32, P < .01); plasma norepinephrine and ROS formation by MNC (r = 0.36, P < .01); and plasma norepinephrine and systolic, diastolic, and mean BP (r = 0.17, P = .04; r = 0.26, P = .02; r = 0.23, P < .01, respectively). In Protocol 2, subtherapeutic doxazosin treatment (1 mg/day) had no significant effect on BP. However doxazosin significantly decreased ROS formation by MNC compared with placebo (P < .01). CONCLUSION: Trait anxiety may increase plasma norepinephrine and increase ROS formation by MNC independent of BP in hypertensive patients.

Adrenergic alpha-1 Receptor Antagonists↗

Relationship between plasma concentrations of cytokines, ratio of CD4 and CD8, lymphocyte proliferative responses, and depressive and anxiety state in bulimia nervosa.

OBJECTIVE: Immunological dysfunction in participants with bulimia nervosa (BN) might be due to not only chaotic eating behavior but also psychological state, such as depression and anxiety, because studies have found a close relationship between depression, anxiety, and immunological dysfunction. METHOD: Participants included 20 females with BN and 14 control females. In eight BN participants, immune function was measured twice, before and after inpatient treatment. Cytokines [interleukin (IL)-1 receptor antagonist, IL-2 soluble receptor alpha, IL-6 soluble receptor (sIL-6r), and tumor necrosis factor soluble receptor II (sTNF-rII)], lymphocyte subsets (CD4 and CD8), and lymphocyte proliferative responses were measured. RESULTS: There were no differences in plasma cytokine levels or lymphocyte subsets between the BN participants and the controls. Conversely, lymphocyte proliferative responses were significantly lower in BN participants than in the controls. Lymphocyte proliferative responses negatively correlated with anxiety trait and improved with an improvement of bulimic state. CONCLUSION: The comorbid nonspecific anxiety trait significantly contributes to suppressing lymphocyte proliferative responses in BN participants.

Adult↗

[Animal model of eating disorders].

Patients with eating disorders are increasing in number. Some neurocircuits concerned with feeding behavior might be dysfunctional in these patients with repeated expression of disorganized eating behavior like long-lasting dieting. These neuronal, or endocrinological dysfunctions might even be enhanced by psychological stress. To understand the biological bases of eating disorders is necessary to establish effective treatment. According to the clinical features of the patients, we have conducted some rat studies. We have found that space restriction stress enhances rebound hyperphagia induced by time-restricted scheduled feeding, and propose the phenomenon as a possible rat model of binge eating. We can speculate some part of the biological bases of human eating disorders, and effective prevention and treatment through such animal models.

Animals↗

A comparative proteomic analysis of the rat brain during rebound hyperphagia induced by space-restriction.

Although neurochemical changes have been reported in the brain in animal models of binge eating, biochemical changes of specific proteins in the brain are unknown. Our aim was to elucidate brain proteins altered in rats during enhanced rebound hyperphargia. Rats were deprived of food for 22 h/day for 6 days, then allowed free access to food for 24 h in normal cages (rebound hyperphargia) or in space-restricted cages (enhanced rebound hyperphargia). Proteins extracted from the rat brain were separated by two-dimensional gel electrophoresis, and compared with those from control rats freely fed for 7 days in normal cages. Proteins expressed differently from controls were identified by N-terminal amino acid sequencing and mass fingerprinting using a MALDI-TOF mass spectrometer. Among proteins in the corpus striatum, frontal lobe, hippocampus and thalamus/hypothalamus, ubiquitin C-terminal hydrolase L1 and peroxiredoxin 2 decreased in the hippocampus and phosphatidylethanolamine-binding protein increased in the thalamus/hypothalamus of rats with the enhanced rebound hyperphargia induced by space-restriction. In this study, we first demonstrated that three brain proteins changed in rats during enhanced rebound hyperphagia. These proteins might have pathophysiologic relevance to binge eating.

Animals↗

Reduction of anxiety after restricted feeding in the rat: implication for eating disorders.

BACKGROUND: Eating-disorder patients exhibit not only abnormal eating attitudes but also pathologic anxiety-like behaviors. The specific nature of the relationship between dieting and anxiety-like behavior is unknown. METHODS: To investigate the adaptational changes that resulted from chronic restricted scheduled feeding (2-hour access per day for 2 weeks) and subsequent free refeeding, longitudinal changes in the microstructure of feeding behavior were studied in male rats. To study the relationship between restricted feeding and anxiety-like behavior, separate rats were tested in the elevated plus-maze under the following conditions: 1) free feeding; 2) acute food restriction (2-hour access for 1 day); 3) chronic food restriction (for 10 days); or 4) postrecovery (after 10 days of free feeding subsequent to chronic food restriction). RESULTS: The effects of chronic food restriction on meal structure diminished within a few days after refeeding. Decreased anxiety-like behavior was seen during acute and chronic food restriction and did not reflect nonspecific behavioral activation. Anxiolytic-like effects persisted after 10 days of refeeding. CONCLUSIONS: Chronic food restriction produced reductions in anxiety-like behavior that persisted beyond the normalization of food intake patterns. The findings might have etiologic and pathophysiologic relevance for the restrained eating pattern in eating-disorder patients with comorbid anxious symptoms.

Adaptation, Psychological↗

Local perfusion of mCPP into ventromedial hypothalamic nucleus, but not into lateral hypothalamic area and frontal cortex, inhibits food intake in rats.

RATIONALE: The serotonergic (5-hydroxytryptamine, 5-HT) system is extensively implicated in feeding behavior. In recent years, 5-HT receptors have been classified into 14 subtypes, and activation of 5-HT1B and 5-HT2C receptors inhibits food intake in rats. However, the precise functions in local brain areas of these receptor subtypes are unclear. OBJECTIVES: Frontal cortex (FC), lateral hypothalamic area (LH), or ventromedial hypothalamic nucleus (VMH) are involved in control of feeding behavior. We investigated the effects of 5-HT1B and 5-HT2C receptor stimulations in the three local brain areas on feeding behavior and on 5-HT metabolism. METHODS: We perfused mCPP, 5-HT(1B/2C) agonist, at multiple doses via a microdialysis probe into the three local brain areas and observed food intake. Extracellular concentrations of 5-HT and 5-HIAA were measured simultaneously. RESULTS: Perfusion of 1 mM mCPP into VMH, but not into LH nor FC at any dose, induced significant reduction of food intake compared with control. The extracellular concentrations of 5-HT were markedly increased in all three areas, but the concentrations of 5-HIAA were not changed by mCPP perfusions. CONCLUSIONS: These results indicate that the effects of 5-HT1B or 5-HT2C receptor activation on feeding behaviors depended on the brain regions, and that 5-HT1B or 5-HT2C receptors in VMH, but not in FC or in LH, play important roles in the regulation of food intake. The results also suggested that mCPP acts not only as a 5-HT(1B/2C) agonist, but also as a 5-HT releaser or as a re-uptake inhibitor. Further studies using antagonists should be conducted.

Animals↗

Effect of menatetrenone (vitamin K2) treatment on bone loss in patients with anorexia nervosa.

Osteoporosis is a common complication of anorexia nervosa (AN). Although weight recovery and resumption of menses are important goals in AN treatment, they are often achieved only after a prolonged period of recovery. Therefore, it becomes important to find therapies with the potential to prevent further decreases in bone mineral density (BMD). We conducted a non-randomized study of the effects of menatetrenone (vitamin K2) on bone loss in patients with AN. Lumbar BMD was longitudinally measured by Dual Energy X-ray Absorptiometry (DXA) in 10 patients with AN who chose to receive menatetrenone treatment (MED+ group) and 11 patients who did not (MED- group). During the mean 0.9-year follow-up period, the BMD of the lumbar vertebrae of the MED+ group decreased significantly less than that of the MED- group (-2.8% and -6.9%, respectively). Among bone metabolism markers, gamma-carboxyglutamic acid osteocalcin significantly increased (128.6% and 28.3%, respectively) and urine deoxypyridinoline significantly decreased (-44.5% and -13.7%, respectively) more in the MED+ group than in the MED- group. These differences in BMD and bone metabolism markers may be attributable to menatetrenone treatment. The results suggest that menatetrenone may be beneficial in the prevention of bone loss in patients with AN. Randomized placebo-controlled studies are needed to confirm these findings.

Adult↗

Clinical features in two cases with musical obsessions who successfully responded to clomipramine.

Clinical features in two cases with musical obsessions are presented to discuss phenomenological and psychopharmacological differences from those in patients with musical hallucinations. The present patients commonly experienced music as an internally generated cognitive product accompanied by full insight into the senselessness of the symptoms. They also attempted to suppress the musical symptoms or to neutralize them with other thoughts. Thus, despite no covert or systematic compulsive behaviors, the musical symptoms of the present cases are consistent with the phenomenological nature of obsessive-compulsive disorder defined in DSM-IV. In addition, in contrast to previous case reports of musical hallucinations, the present patients failed to respond to neuroleptics, but showed significant response to an adequate trial of clomipramine. Thus, their symptoms appear to be phenomenologically and biologically distinct from musical hallucinations, especially those characteristic of schizophrenia.

Adult↗

Repetitive self-mutilation among Japanese eating disorder patients with drug use disorder: comparison with patients with methamphetamine use disorder.

Repetitive self-mutilation and drug use disorder are less prevalent in Japan, although the prevalence of eating disorder is comparable with rates in Western countries. However, repetitive self-mutilation has not previously been described in relation to eating disorder and drug use disorder in Japan. Subjects consisted of 19 patients with eating disorders and drug use disorders (ED+DUD) and 12 patients with methamphetamine use disorders (MAP). Subjects were drawn from 180 patients who were referred because of eating disorders and 22 patients who were referred because of methamphetamine-related problems. All subjects underwent a semistructured interview. Repetitive self-mutilation tended to be more prevalent among ED+DUD patients than MAP patients. Conversely, history of oppositional defiant disorder and antisocial personality disorder tended to be more prevalent in MAP patients than in ED+DUD patients. The low prevalence of repetitive self-mutilation appears to be due to low risk factors in Japan, even though the pathogenesis of these behaviors seems to be universal.

Adult↗

[Frégoli symptom].

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Antidepressive Agents↗

Drug use disorders in Japanese eating disorder patients.

A previous questionnaire study suggested that drug use disorder (DUD: abuse/dependence on drugs, other than alcohol) in Japanese eating disorder (ED) patients was less prevalent than in Western countries, although eating and drug use disorders have spread simultaneously in Western countries. However, the precise prevalence and comorbidity features remain unknown. Subjects consisted of 62 patients with anorexia nervosa restricting type; 48 patients with anorexia nervosa binge eating/purging type; and 75 patients with bulimia nervosa purging type. The Japanese version of the Structured Clinical Interview for DSM-III-R; the Structured Clinical Interview for DSM-III-R Personality Disorders; and the supplement module of the Schedule for Affective Disorders and Schizophrenia-Lifetime version were used for the interview. Sixteen (8.6%, 95% CI = 4.6-12.7%) patients had lifetime diagnoses of DUD. Drugs were solvent fumes or benzodiazepines, and only one patient had been dependent on methamphetamine. More than half of the patients with lifetime DUD diagnoses were multi-impulsivitists. On multivariate analysis, DUD was significantly linked with childhood parental loss, history of conduct disorder and borderline personality disorder. Thus, the prevalence of DUD in Japanese ED patients was indeed lower than that in Western countries. However, similar comorbidity was found in ED patients with DUD compared with that of those in Western countries. The current study suggests that ED and DUD have different origins, although they share the feature of impulsivity. Further study in the general population is needed to clarify these issues.

Adolescent↗