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Biomedical subjects

A Inui

Publications and source records attributed to A Inui.

At least 55 records · Page 3Linked to original sources

Thioperamide, a histamine H3 receptor antagonist, powerfully suppresses peptide YY-induced food intake in rats.

BACKGROUND: Whether or not peptide YY (PYY)-induced hyperphagia is modified by the histaminergic system in the brain is not yet known. METHODS: We investigated the effect on feeding of intracerebroventricular (ICV) administration of a specific histamine H3 receptor antagonist prior to ICV administration of PYY in rats. RESULTS: PYY (1, 3, and 10 micrograms/10 microL) strongly induced feeding behavior in a dose-dependent manner in sated rats. The 4-hour food intake induced by 3 micrograms/10 microL of PYY was equal to that induced by a 16-hour fast. The ICV administration of thioperamide (40.8, 122.4, and 408.5 micrograms/10 microL) did not suppress the 4-hour food intake induced by 16-hour fasting; however, thioperamide produced dose-dependent and strong inhibition of hyperphagia induced by a 3-microgram dose of PYY. CONCLUSIONS: These results suggest that the effect of PYY on appetite is different than that induced by fasting and may involve a histaminergic mechanism.

Analysis of Variance↗

GBV-C/HGV infection in children with chronic hepatitis C.

The role of GB virus-C/hepatitis G virus (GBV-C/HGV), a recently identified member of the Flaviviridae family, in children with liver disease is not well understood. The aims of this study were to evaluate the prevalence of GBV-C/HGV and to clarify its pathogenic role in young patients with chronic hepatitis C. Sixty-four Japanese children and adolescents with chronic hepatitis C virus (HCV) infection, with a mean age of 9.8 years, were evaluated retrospectively. Twenty-one (32.8%) of the 64 patients were positive for serum GBV-C/HGV RNA. Only 1 (1.6%) of the 64 patients was positive for antibody against the envelope protein E2 of GBV-C/HGV (anti-E2) and GBV-C/HGV. None of them was positive for anti-E2 alone. There was no significant difference in clinical, virological, or histological characteristics between GBV-C/HGV-positive and GBV-C/HGV-negative patients, except for underlying malignant disease. There was no evidence that GBV-C/HGV might affect the response of HCV to interferon therapy in young patients with chronic hepatitis C. The prevalence of GBV-C/HGV infection in young patients with chronic hepatitis C is similar to that in adult patients with chronic hepatitis C, but E2-seroconversion is observed infrequently. Underlying malignant disease is a risk factor for GBV-C/HGV viremia. GBV-C/HGV does not seem to affect the clinical course of young patients with chronic hepatitis C.

Adolescent↗

Generalized peritonitis with pneumoperitoneum caused by the spontaneous perforation of pyometra without malignancy: report of a case.

Spontaneous perforation is a very rare complication of pyometra. We report herein the case of an 88-year-old woman who presented with muscular rigidity and free air on abdominal X-ray films. Perforation of the gastrointestinal tract was diagnosed preoperatively, and an emergency laparotomy was performed. A total hysterectomy with bilateral salpingo-oophorectomy was carried out under the diagnosis of generalized peritonitis caused by the spontaneous perforation of pyometra. The culture of purulent fluid from the abdominal cavity showed only Escherichia coli, with no anaerobic bacteria. Histological examination revealed pyometra with necrosis of the endometrium and no evidence of malignancy. The patient was discharged on postoperative day 68 without any major complications. Pyometra is an unusual cause of peritonitis, but it must be considered as a possible diagnosis in elderly women presenting with an acute abdomen. Following this case report, we discuss the problems associated with establishing a correct preoperative diagnosis of generalized peritonitis caused by the spontaneous perforation of pyometra.

Aged↗

Decreased food intake and body weight in pancreatic polypeptide-overexpressing mice.

BACKGROUND & AIMS: Pancreatic polypeptide (PP) is a 36-amino acid hormone produced by F cells within the pancreatic islets and the exocrine pancreas. The definitive function of PP in mammalian physiology remains to be determined. This study examined the effects of chronic overexpression of PP through the development of PP transgenic mice. METHODS: PP transgenic mice were created by using mouse PP complementary DNA under the control of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid promoter (pCAGGS expression vector). RESULTS: A unique line of transgenic mice was created that overexpresses PP in the pancreatic islets with low levels of expression in other tissues including the brain. Plasma PP concentrations were more than 20 times higher than those of control littermates. However, PP overproduction led to postnatal lethality in half of the pups because of markedly decreased milk intake. The remaining PP transgenic mice gained less weight with specifically reduced food intake and fat mass compared with controls, a result that was more evident in male than in female mice. The transgenic mice exhibited a reduced rate of gastric emptying of a solid meal but had normal oxygen consumption and fasting leptin levels. Immunoneutralization with anti-PP antiserum reversed the phenotypic changes of transgenic animals. CONCLUSIONS: PP could be involved in feeding and body weight regulation partly through regulation of gastric emptying.

Animals↗

Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice.

BACKGROUND & AIMS: Gastric emptying plays an important role in regulating food intake. This study was designed to investigate whether intraperitoneally injected urocortin reduces gastric emptying, feeding, and body weight in lean and ob/ob obese mice. METHODS: Food intake and body weight were measured after intraperitoneal injections of one of the following: urocortin, deamidated form of urocortin (urocortin OH), corticotropin-releasing factor (CRF), CRF6-33, cholecystokinin octapeptide (CCK-8), and leptin in 16-hour food-deprived animals. Gastric emptying was assessed 2, 4, or 8 hours after intraperitoneal injection. Repeated injections of urocortin were continued for 5 days in ob/ob mice. RESULTS: Urocortin (0.003-3 nmol) dose-dependently and potently decreased food intake and body weight gain in lean mice. The ranking order of potency was urocortin > urocortin OH >/= CRF > CCK-8 > CRF6-33 > leptin. Gastric emptying was also potently reduced by urocortin with a similar ranking order of potency of urocortin > CRF > urocortin OH > CCK-8. Simultaneous administration of urocortin and CRF receptor antagonist, alpha-helical CRF9-41, blocked the effects of urocortin. Urocortin reduced food intake and body weight gain, as well as the rate of gastric emptying, in ob/ob mice, which was significantly faster than that of lean mice. Five daily injections of urocortin significantly lowered body weight and improved glycemic control in ob/ob mice. CONCLUSIONS: The urocortin-induced decrease in food intake and body weight in lean and ob/ob mice is closely related to gastric emptying and opens new possibilities for the treatment of obesity.

Animals↗

Feeding and body-weight regulation by hypothalamic neuropeptides--mediation of the actions of leptin.

Neuropeptides are essential for the regulation of appetite and body weight within the hypothalamus. The understanding of the neuropeptide regulation of energy homeostasis has been greatly advanced by the recent discovery of leptin, the protein product of the obese gene (ob). Significant new insights into the relationship between peripheral adiposity signals and their impact on the hypothalamic neuropeptide signaling circuitry have provided some crucial missing links in the negative-feedback regulation of appetite and body weight. The neuropeptide Y orexigenic network is a final common pathway for this signaling cascade and, along with feeding-inhibitory neuropeptides such as melanocortin, corticotropin-releasing factor and glucagon-like peptide 1, it is a major target through which leptin exerts a regulatory tonic restraint on body adiposity.

Animals↗

Mouse pancreatic polypeptide modulates food intake, while not influencing anxiety in mice.

This study was designed to investigate the effects of synthetic mouse pancreatic polypeptide (mPP) on feeding and anxiety in mice. The intracerebroventricular (i.c.v.) injection of mPP (0.003-3 nmol) dose-dependently increased food intake. A significant increase was observed 20 min after i.c.v. injection and continued for 4 h. The intraperitoneal (i.p.) injection of mPP (0.03-30 nmol) dose-dependently decreased food intake. A significant decrease was observed 20 min after i.p. injection and continued for 4 h. In the elevated plus maze test, the i.c.v. injection of mPP (0.003-3 nmol) did not affect anxiety behavior. These results suggest that mPP modulates food intake and the Y4 receptor in the brain may contribute to the regulation of feeding, whereas appearing not to influence anxiety in mice.

Animals↗

Neuropeptide Y: a key molecule in anorexia and cachexia in wasting disorders?

Anorexia and body weight loss are characteristic of many diseases, including cancer and AIDS. Recent studies indicate that inflammatory cytokines, such as interleukin 1, the interleukin 6 subfamily and tumor necrosis factor, induce anorexia and cachexia by inhibiting the normal adaptive feeding response to energy deficits. Here, I discuss the evidence for and against a central role for neuropeptide Y and leptin in anorexia and cachexia.

Animals↗

Severe late acute allograft rejection in a child after living-related auxiliary partial orthotopic liver transplantation for ornithine transcarbamylase deficiency.

Auxiliary liver transplantation (ALT) is known to correct liver-based metabolic disorders. However, it remains unclear whether the presence of a native liver influences the long-term prognosis of ALT for metabolic diseases. We reported on a 4-yr-old girl who had undergone living-related auxiliary partial orthotopic liver transplantation (APOLT) for ornithine transcarbamylase deficiency and experienced severe late acute rejection 18 months after liver transplantation, during weaning of immunosuppressive agents. Results of histological analysis of the graft indicated very severe acute rejection (rejection activity index, 9/9), and computed tomography revealed graft liver atrophy. These observations suggest the possibility that severe rejection might occur in APOLT, especially during weaning of immunosuppression.

Acute Disease↗

Hepatitis B precore mutant in children with chronic hepatitis B virus infection.

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.

Adolescent↗

Intracerebroventricularly administered corticotropin-releasing factor inhibits food intake and produces anxiety-like behaviour at very low doses in mice.

AIM: Previous studies have demonstrated that corticotropin-releasing factor (CRF) produces behavioural, physiological and immunological responses similar to those induced by stress. However, these findings have been validated largely in laboratory rats. METHODS: We examined the effects of intracerebroventricular (i.c.v.) administration of CRF on anxiety and food intake in mice. Using the elevated-plus maze, we measured anxiety levels after i.c.v. CRF in mice. We also measured food intake for 2 h after i.c.v. CRF. RESULTS: CRF increased the normal preference for the closed arms of the maze at a very low dose of 3 pmol, indicating an anxiogenic effect. CRF powerfully suppressed food intake at the doses of 3-300 pmol for over 2 h. CONCLUSION: Our results demonstrate that i.c.v. CRF evokes anxiogenic behaviour and suppresses feeding with the same dose-response relationships in mice. CRF may thus play a role in integrating the overall responses to stress through co-ordinated actions in the brain of this species.

Animals↗

[An infant of autoimmune hepatitis (type I) with cirrhosis].

A 6 year-old boy with autoimmune hepatitis accompanied with cirrhosis was reported. He was admitted to our hospital because of abdominal distention, high fever, and diarrhea. Laboratory examination revealed abnormalities in hepatic function, cholestasis, anemia, thrombocytopenia, hypoalbuminemia, hypocomplementemia, and low concentration of coagulation factors. Abdominal MRI, and asialoglycoprotein receptor-mediated liver scintigraphy strongly indicated liver cirrhosis. Viral hepatitis, Wilson's disease, and antitrypsin deficiency were excluded serologically. Instead, hypergammaglobulinemia, and positive antinuclear antibody suggested autoimmune hepatitis, and the survey of anti-mitochondrial antibody, anti-smooth muscle antibody, and anti-LKM-1 antibody was negative, indicating type I autoimmune hepatitis. Finally, the histology of liver biopsy specimen indicating the destruction of hepatic lobular architecture, dense mononuclear cell infiltrates, and severe fibrosis confirmed the diagnosis. He was treated firstly with methylprednisolone pulses, and then prednisolone p.o. + azathioprine p.o. All of the abnormal laboratory parameters improved to normal levels, indicating that the immunosuppressive therapy will be effective for the severe AIH with cirrhosis.

Child↗

Selective portal blood flow diversion in auxiliary partial orthotopic liver transplantation to induce regeneration of the graft.

Experience with auxiliary partial orthotopic liver transplantation (APOLT) is still very limited and many questions remain to be solved. In this article, we present the case of a 5-year-old girl with ornithine transcarbamylase deficiency who initially did well after APOLT. During a severe rejection episode 16 months after transplantation, she developed encephalopathy and hyperammonemia. Despite a good clinical and histopathological response to antirejection therapy, the graft had become smaller and the native liver had undergone compensatory hypertrophy. After we surgically ligated the right portal branch, the graft recovered and the patient was able to stop her medication 1 month after surgery. We have estimated that the minimum volume of normal liver required to correct the metabolic defect in ornithine transcarbamylase deficiency is 8 cm3/kg. The ligation of the right portal branch was a safe and effective method of inducing a gradual and progressive involution of the hypertrophic native liver and regeneration of the atrophic graft.

Atrophy↗

Thioperamide, a histamine H3 receptor antagonist, suppresses NPY-but not dynorphin A-induced feeding in rats.

Whether or not neuropeptide Y (NPY)-induced feeding in rats is influenced by the histaminergic system in the brain was investigated by intracerebroventricular (i.c.v.) administration of a selective histamine H3 receptor antagonist prior to i.c.v. administration of NPY. NPY (10 microg/10 microl) strongly induced feeding in sated rats during the light phase of the day. Dynorphin A1-17 (10 microg/10 microl), a kappa-opioid agonist, and rat pancreatic polypeptide (rPP, 30 microg/10 microl) also stimulated ingestive behavior in sated rats, but food intake in both cases was less than that induced by NPY. Thioperamide maleate, a specific histamine H3 receptor antagonist (408.5 microg/10 microl) reduced the feeding response to NPY by 52% (P < 0.0001), but not to dynorphin A1-17 and rPP. Thioperamide at i.c.v. doses of 40.8-408.5 microg/10 microl had no effect on food intake in sated rats. These results suggest that the thioperamide may have a specific effect on NPY receptor-mediated neuronal systems related to feeding.

Animals↗

Endomorphins have orexigenic and anxiolytic activities in mice.

This study was designed to investigate the effects of endomorphin 1 and 2, recently identified mu-opioid receptor selective peptides, on food intake and anxiety in non-food-deprived mice. The intracerebroventricular (i.c.v.) injection of either endomorphin 1 or 2 (0.03-30 nmol) increased food intake in a dose-related manner. A significant increase was observed 20 min after i.c.v. injection of endomorphin 1 or 2 and continued for 4 h. In the elevated plus maze test, the i.c.v. injection of endomorphin 1 (30 nmol) significantly decreased the normal preference for the closed arms. These results suggest that endomorphin produces orexigenic and anxiolytic effects, and that the mu-opioid receptor contributes to the regulation of feeding and anxiety in mice.

Animals↗