Effects of gastric inhibitory polypeptide and glucagon on portal venous and hepatic arterial flow in conscious dogs

Gastric inhibitory polypeptide (GIP) has considerable structural homology with glucagon, which is known to increase liver blood flow. We compared the effects of GIP on portal venous and hepatic arterial flow with those of glucagon in conscious dogs. Injection of GIP significantly increased portal venous flow in a dose-related manner (by 7%, 15%, and 46% at doses of 1, 100, and 500 pmol/kg, respectively). The increase in portal venous flow induced by GIP and glucagon was comparable; however, the increase in portal venous flow after GIP injection reached its peak significantly earlier than that after glucagon injection. Hepatic arterial flow decreased after GIP injection (by 17%, 21%, and 35% at doses of 1, 100, and 500 pmol/kg, respectively), whereas it was not altered by glucagon. Thus, GIP causes significant changes in both portal venous and hepatic arterial flow in conscious dogs. Although structurally related, GIP and glucagon may influence liver blood flow through different mechanisms.Supported by a grant from the Ministry of Education, Japan (No. A-02404052)     

Evaluation of the efficacy of an Helicobacter pylori eradication treatment for idiopathic thrombocytopenic purpura patients]

The relationship between Helicobacter pylori (H. pylori) and gastric diseases (e.g. peptic ulcer, MALT lymphoma, and stomach cancer) has been widely accepted. Recent studies have also suggested an association between H. pylori infection and idiopathic thrombocytopenic purpura (ITP). In this study, an H. pylori eradication treatment was administered to 20 ITP patients and elucidated for its effectiveness. Among those 20 patients, H. pylori infection was confirmed in 17 (85%) through a C14 urea breath test, a rapid urease test, or a culture examination of a biopsied sample obtained by gastrointestinal endoscopy. Although the other 3 were negative to H. pylori, the H. pylori eradication treatment was also attempted because no other effective treatments had been established at the time of this study. In the H. pylori eradication treatment, lansoprazole (LPZ) 60 mg bid, amoxicillin (AMPC) 1500 mg bid, and clarithromycin (CAM) 400 mg bid were given to each patient for 7 days. For 4 cases, CAM was replaced with metronidazole (MNZ) 750 mg bid. The patients whose H. pylori infection was not eradicated after the first treatment received the re-eradication treatment with LPZ 60 mg bid, AMPC 1500 mg bid, and MNZ 750 mg bid for 7 days. After the treatments, the success of eradicating H. pylori was confirmed in all 17 H. pylori positive patients. In addition, platelet recovery was obtained in 11/20 patients (55%), which included 2 H. pylori negative patients and 2 patients whose H. pylori eradication was not successful after the first treatment. No relationship was found between the eradication effectiveness and the following clinical parameters: age, gender, previous therapies, disease duration, presence of anti-nucleus antibody, endoscopic atrophic change in the stomach, or kinds of antibiotics used for the treatment. These results support the efficacy of an H. pylori eradication treatment for ITP patients. A noteworthy result of this study was that an increase of platelet count was observed not only in H. pylori positive ITP patients, but also in 2 out of 3 H. pylori negative ITP patients after H. pylori eradication. Further studies are required to elucidate the efficacy of H. pylori eradication therapy in the patients negative for H. pylori.     

Preventive Effects of Renin-angiotensin System Inhibitors on Oxaliplatin-induced Peripheral Neuropathy: A Retrospective Observational Study

Purpose

Oxaliplatin-induced peripheral neuropathy has remained an unresolved issue in clinical practice. Our previous study hypothesized that inhibition of the renin-angiotensin system (RAS) may produce a preventive effect on oxaliplatin-induced neuropathy. The aim of this study was to clarify whether RAS inhibitors prevent oxaliplatin-induced peripheral neuropathy.

Postpartum onset of acute heart failure possibly due to postpartum autoimmune myocarditis. A report of three cases

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases have transient dysfunction of affected organs. Cardiac dysfunction developed after delivery is called postpartum or peripartum cardiomyopathy. However, the aetiology of the disease is not clarified yet. Here we report three cases that developed acute heart failure in the postpartum period. One was complicated with an atrioventricular block and postpartum autoimmune thyroiditis. All patients recovered to normal cardiac function or pre-attack condition after 1 month of therapy with conventional drugs and bed rest. All three had positive antiheart antibody detected by indirect immunofluorescence assay, and one had antibody to heart myosin detected by enzyme-linked immunosorbent assay. Moreover, one of two patients examined revealed lymphocytic infiltration by endomyocardial biopsy. Antibodies to 26 viruses were not elevated significantly during the first 2 weeks after admission in any case. It is strongly suggested that heart failure is induced by postpartum autoimmune myocarditis, and thus clinicians should be aware of this disease.     

Genetic analysis of radiation-associated rectal cancer

Genetic aberrations in radiation-associated colorectal cancer have not been studied in detail. We analyzed genetic aberrations in five rectal cancers that developed long after radiotherapy had been performed for cervical cancer. Microsatellite instability (MSI) in tumors was examined at five loci: D2S123, D3S966, TP53, DCC, and BAT26. Mutation of simple repeat sequences within the hMSH3, BAX, and transforming growth factor type II receptor (TGFRII) genes was examined by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP). Mutation of p53 exons 5–8 was examined by PCR-SSP and direct sequencing. Mutations of the K-ras gene were analyzed by two-step PCR. No MSI was found in tumor specimens at any of the loci examined, and no mutations in the target genes were observed. K-ras mutation was detected in two carcinomas, but not in their irradiated normal mucosa, while p53 mutation was observed in another two carcinomas, but not in their irradiated normal mucosa. Our results suggest that the radiation-associated rectal carcinomas examined in this study did not develop through the mutator phenotype pathway; rather, tumorigenesis was probably mediated through the multistep carcinogenesis pathway.     

A new antidiabetic agent (JTT-501) rapidly stimulates glucose disposal rates by enhancing insulin signal transduction in skeletal muscle

Summary A newly synthesized antidiabetic agent, JTT-501 is an isoxazolidinedione rather than a thiazolidinedione. An oral dose of JTT-501 (100 mg · kg^–1· day^–1) given to 12-week-old male Zucker fatty rats for 7 days led to the amelioration of both hyperinsulinaemia (40 % of non-treated) and hypertriglyceridaemia (23 % of non-treated) as well as a 2.4-fold increased insulin sensitivity as determined by a euglycaemic insulin clamp. In our study, we further evaluated the acute effect of JTT-501 on both the glucose infusion rates (GIR) and insulin signalling in skeletal muscle. Male Sprague-Dawley (SD) rats aged 10 weeks were injected intravenously with JTT-501 (5 mg/kg) and then a euglycaemic insulin clamp was initiated and glucose infusion rates monitored for 150 min. We found that this treatment increased the glucose infusion rate by 33 % during the last 30 min in SD rats. After the clamp had been initiated for 30 min, the insulin-stimulated phosphatidylinositol 3-kinase (PI3-kinase) activities co-immunoprecipitated with insulin receptor substrate 1 (IRS-1) were also enhanced, resulting in increased glycogen synthase activities in the soleus muscles. Treatment with JTT-501 also enhanced the phosphorylation of insulin receptors and insulin receptor-substrate 1 rapidly as well as the phosphatidylinositol 3-kinase activities, which were stimulated by a bolus injection of insulin. Similarly, JTT-501 stimulated the glucose infusion rate by 30 % and enhanced insulin signalling in Zucker fatty rats. In conclusion, a newly developed isoxazolidinedione, JTT-501, rapidly potentiates the insulin sensitivity of skeletal muscle by enhancing insulin signalling and could be useful for the treatment of insulin-resistant diabetic subjects. [Diabetologia (1999) 42: 151–159] Received: 2 June 1998 and in final revised form: 2 October 1998     

Effect of pitch–space correspondence on sound-induced visual motion perception

The brain tends to associate specific features of stimuli across sensory modalities. The pitch of a sound is for example associated with spatial elevation such that higher-pitched sounds are felt as being “up” in space and lower-pitched sounds as being “down.” Here we investigated whether changes in the pitch of sounds could be effective for visual motion perception similar to those in the location of sounds. We demonstrated that only sounds that alternate in up/down location induced illusory vertical motion of a static visual stimulus, while sounds that alternate in higher/lower pitch did not induce this illusion. The pitch of a sound did not even modulate the visual motion perception induced by sounds alternating in up/down location. Interestingly, though, sounds alternating in higher/lower pitch could become a driver for visual motion if they were paired in a previous exposure phase with vertical visual apparent motion. Thus, only after prolonged exposure, the pitch of a sound became an inducer for upper/lower visual motion. This occurred even if during exposure the pitch and location of the sounds were paired in an incongruent fashion. These findings indicate that pitch–space correspondence is not so strong to drive or modulate visual motion perception. However, associative exposure could increase the saliency of pitch–space relationships and then the pitch could induce visual motion perception by itself.     

The optimal trough-guided monitoring of vancomycin in children: Systematic review and meta-analyses

We carried out a systematic review and meta-analysis exploring the relationship between vancomycin (VCM) trough concentrations and its effectiveness and nephrotoxicity in pediatric patients. We conducted our analysis using MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials as electronic databases (June 29, 2019). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified 16 studies that were eligible for the meta-analysis. A total of 351 and 3,266 patients were included in the analysis for effectiveness and nephrotoxicity, respectively. Pediatric MRSA infection patients with VCM trough concentrations ≥ 10 μg/mL had significantly lower treatment failure rates (OR 0.54, 95% CI 0.30–0.96). The incidence of nephrotoxicity was significantly higher in trough concentrations ≥ 15 μg/mL than when they were < 15 μg/mL (OR 3.02, 95% CI 2.08–4.38). We identified the optimal VCM trough concentrations associated with effectiveness and nephrotoxicity in pediatric patients with MRSA infection. Further prospective studies are needed to find optimal dosing and monitoring strategy on VCM in pediatric population.     

Unilateral pulmonary agenesis associated with oesophageal atresia and tracheoesophageal fistula: A case report with prenatal diagnosis

We describe herein a case of unilateral pulmonary agenesis (PA) with oesophageal atresia (EA)/tracheoesophageal fistula (TEF) that was diagnosed prenatally and repaired by esophagoesophagostomy with stable postoperative course. The patient was born at 34 weeks gestation, after ultrasonography at 22 weeks gestation showed possible right-sided diaphragmatic eventration or PA and EA was subsequently suspected due to hydramnios. The initial X-ray showed mediastinal shift to the right, and coil up sign of the nasogastric tube, without intracardiac anomaly. Immediately after the diagnosis of EA/TEF and unilateral PA on day 0, the patient was intubated in the operating room, and a gastrostomy tube was placed. After pulmonary status stabilized, at 4 days old, EA/TEF was repaired through a thoracotomy in the right 4^th intercostal space. The right main bronchus was noted to continue into the distal oesophagus; this fistula was ligated and divided, and a single-layer esophagoesophagostomy was performed under mild tension with one vertebral gap. The neonate was maintained on mechanical ventilation and gradually weaned to extubation at 7 days old. The postoperative course was uneventful, with the exception of prolonged jaundice that emerged at 3 months old. Laparoscopic cholangiography at that time excluded biliary atresia, and jaundice resolved spontaneously. The patient has not shown any respiratory symptoms or feeding difficulties as of the 12-month follow-up.