Telmisartan treatment decreases visceral fat accumulation and improves serum levels of adiponectin and vascular inflammation markers in Japanese hypertensive patients.

Hypertension contributes to the occurrence and progression of cardiovascular diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to activate the peroxisome proliferator-activated receptor gamma and improve insulin sensitivity. We investigated the effects of telmisartan treatment on visceral fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive patients. This was an open-label, non-controlled study. Twenty-eight essential hypertensive patients (22 men and 6 women; age 60.6+/-1.9 years; body mass index [BMI] 25.5+/-0.6 kg/m(2)) participated. Fat area was assessed with computerized tomography. All the subjects were started on telmisartan 40 mg/day, which was increased to 80 mg/day to achieve the blood pressure target of less than 130/80 mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan treatment. There were significant reductions in visceral fat area (from 103.1+/-7.9 to 93.3+/-8.4 cm(2), p<0.01) and pulse wave velocity (from 1,706+/-52 to 1,587+/-51 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum high-density lipoprotein cholesterol (from 5.06+/-0.15 to 5.32+/-0.13 mmol/L, p<0.05) and adiponectin levels (from 8.27+/-0.76 to 9.13+/-0.81 microg/mL, p<0.05) were observed. Also, there were reductions in the interleukin-6 level (from 2.26+/-0.27 to 1.60+/-0.14 pg/mL, p<0.01). We also conducted these investigations in male subjects alone and similar findings were obtained for all of these parameters. In conclusion, telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin.     

Results of a survey of community-acquired-pneumonia and evaluation of old and new Japanese Respiratory Society guidelines]

We evaluated the usefulness of domestic and foreign guidelines for the diagnosis and treatment of patients with community-acquired-pneumonia at 23 institutions in 6 prefectures of the Tohoku Area, from December 2003 to November 2004. Based on the old and new Japanese Respiratory Society (JRS) guidelines, we evaluated severity, clinical efficacy and detection of atypical pneumonia. As for severity, the old guidelines led to the diagnosis of an excessive number of 'severe' cases. On the other hand, patients were appropriately diagnosed as having mild, moderate, severe, or very severe disease based on the new JRS guidelines (2005). The severity classification often correlated with the Pneumonia Severity Index (PSI) of the IDSA guidelines. The efficacy rate for patients who were prescribed the recommended drug according to the old JRS guidelines was 85.7% and for those who did not use the recommended drug it was 68.7% (p < 0.001).     

Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus

The role of cervical lymphadenectomy for thoracic esophageal cancer is controversial. This study evaluated the impact of cervical lymphadenectomy on the cervical lymph node metastasis (LNM) and survival rates of patients with esophageal cancer. We analyzed 199 patients who received radical esophagectomy with three-field lymphadenectomy. The overall 5-year survival rate was 49.4%. Cervical LNM was found in 36 (18.1%) out of the 199 patients. The 5-year survival rates of the patients with cervical LNM from upper and mid-esophageal cancers were 71.4% and 35.9%, respectively. However, none of the patients with cervical LNM from lower esophageal cancer survived more than 4 years after esophagectomy. The overall survival of patients with five or more metastatic nodes (5.9%) was significantly worse than that of patients with less than five positive nodes (45.5%). Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus, and with less than five positive nodes.     

Taurine in the mammalian cerebellum: Demonstration by autoradiography with [3H]taurine and immunocytochemistry with antibodies against the taurine-synthesizing enzyme, cysteine-sulfinic acid decarboxylase

Taurine neurons and their dendrites and axons were visualized in the mammalian cerebellum by autoradiography, after in vivo injections of [³H]taurine directly into the cerebellar cortex or deep cerebellar nuclei, and by immunocytochemistry at the light- and electron-microscope levels with antibodies against cysteine-sulfinic acid decarboxylase (CSADCase; L-cysteine-sulfinate carboxylyase, EC 4.1.1.29). Uptake and sequestration of [³H]taurine labeled numerous Purkinje cell somata, primary dendrites, and axons; many granule cell somata, dendrites, and parallel fibers; stellate, basket, and Golgi cells; the larger neurons in all deep cerebellar nuclei; the largest neurons in the lateral vestibular nucleus; and, more rarely, Purkinje cell axonal terminals in the neuropil. The label at all sites was diminished by preinjection into the cerebellum of hypotaurine, p-chloromercuriphenylsulfonic acid, or β-alanine, and was virtually eliminated by strychnine. Immunocytochemical labeling with polyclonal antibodies directed against CSADCase, the enzyme responsible for the synthesis of hypotaurine from cysteine sulfinic acid and taurine from cysteic acid, had a similar distribution. In electron micrographs, immunoreactivity within Purkinje cell somata and dendrites was localized to the Golgi apparatus, the inner plasma membrane, and condensed nonmembranous foci (120 nm in diameter) marked by clumps of peroxidase reaction product. Large Nissl bodies were usually not CSADCase immunoreactive. Numerous immunoreactive granule cells, dendrites, and parallel fibers were recognized. Pretreatment of the animals with colchicine increased the intensity of CSADCase immunoreactivity but did not change the number or distribution of labeled cells. These experiments indicate that taurine is synthesized and involved in a specific uptake process by cerebellar neurons. Neuroglial cells do not synthesize taurine but some neuroglia take up [³H]taurine. These findings call for a reexamination of the physiological function of taurine in the cerebellum. A hypothesis is proposed that taurine may be involved in the regulation of calcium, in dendritic spike generation, and in the inhibition of impulse propagation in major Purkinje cell dendrites.     

Relationship of Eating Patterns and Metabolic Parameters,and Teneligliptin Treatment: Interim Results from Post-marketing Surveillance in Japanese Type 2 Diabetes Patients

Introduction

Healthy eating is a critical aspect of the prevention and management of type 2 diabetes (T2DM). Disrupted eating patterns can result in poor glucose control and increase the likelihood of diabetic complications. Teneligliptin inhibits dipeptidyl peptidase-4 activity for 24 h and suppresses postprandial hyperglycemia after all three daily meals. This interim analysis of data from the large-scale post-marketing surveillance of teneligliptin (RUBY) in Japan examined eating patterns and their relationship with metabolic parameters and diabetic complications. We also examined whether eating patterns affected safety and efficacy of teneligliptin.

Methods

We analyzed baseline data from survey forms collected in RUBY between May 2013 and June 2017, including patient characteristics, metabolic parameters, and eating patterns (eating three meals per day or not; timing of evening meal) before teneligliptin treatment was initiated. Safety and efficacy of 12 months’ teneligliptin (20–40 mg/day) treatment was assessed.

Results

Data from 10,532 patients were available for analysis. Most patients who did not eat three meals per day (n??=757) or who ate their evening meal after 10 PM (n??=206) were 64 years old or younger. At baseline, glycated hemoglobin (HbA1c), fasting blood glucose, triglycerides, total and low-density lipoprotein cholesterol, body mass index, alanine aminotransferase, and aspartate aminotransferase levels were higher in those patients who did not eat three meals per day (p?<?0.05) or who ate their evening meal late (p?<?0.05). Diabetic complications were more common in patients who did not eat three meals per day. Treatment with teneligliptin reduced HbA1c over 6 or 12 months across all eating patterns, with a low incidence of adverse drug reactions.

Conclusions

Eating patterns may be associated with altered metabolic parameters and diabetic complications among Japanese patients with T2DM. Teneligliptin may be well tolerated and improve hyperglycemia in patients with T2DM irrespective of eating patterns.

Funding

Mitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co. Ltd.

Trial Registration Number

Japic CTI-153047.

     

Lewis Blood Group-Related Antigen Expression in Normal Gastric Epithelium, Intestinal Metaplasia, Gastric Adenoma, and Gastric Carcinoma

The expression of blood group-related antigens of the Lewis system in normal gastric mucosa, intestinal metaplasia, gastric adenoma, and gastric carcinoma was examined. Ninety-five percent of normal foveolar epithelial samples stained positive for Lewis^b antigen, whereas only 10.0% expressed Lewis^a antigen. In contrast, intestinal metaplasia specimens had increased Lewis^a antigen expression and slightly decreased Lewis^b antigen expression. A similar pattern of Lewis^a and Lewis^b expression was observed in gastric adenomas and intestinal type adenocarcinomas. Lewis^x and Lewis^y were detected in all normal deep glands, but were not expressed in the majority of intestinal metaplasia specimens. In addition, only 20–40% of gastric adenomas and gastric carcinomas expressed Lewis^x and Lewis^y antigens. These changes in Lewis antigen expression in intestinal metaplasia, adenomas, and intestinal type adenocarcinomas suggest that altered expression of Lewis blood group-related antigens may correlate with cell transformation processes.     

Rat Small Intestinal Goblet Cell Kinetics in the Process of Restitution of Surface Epithelium Subjected to Ischemia–Reperfusion Injury

Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution. Goblet cells reside throughout the length of the intestine and are responsible for the production of mucus. However, a kinetic analysis of goblet cell dynamics of small intestine in restitution has hitherto not been reported. The aim of the present study was to investigate the role of goblet cells in the process of restitution of rat small intestine subjected to ischemia and ischemia–reperfusion injury, and therefore intestinal epithelium from rats subjected to both ischemia and ischemia–reperfusion was studied. Detachment of enterocytes was observed after 5-min of reperfusion. After 20–30 minutes of reperfusion, the denuded villous tips were covered with goblet cells. Within 75 min of reperfusion the epithelium restitution was complete. On the other hand, restitution was not observed in ischemia group. These data suggest that goblet cells may play an important role in restitution after ischemia–reperfusion injury.