Peroxisome proliferator-activated receptor delta (PPARdelta), a novel target site for drug discovery in metabolic syndrome.

The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)alpha and gamma agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPARdelta functions is lagging behind because specific PPARdelta agonists have not been developed. The appearance of new PPARdelta agonists is brightening the prospects for elucidating the physiological role of PPARdelta. PPARdelta is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPARdelta agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPARdelta agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPARdelta may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPARdelta agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPARdelta itself and its agonists in the future.     

Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.     

Independent determinants of second derivative of the finger photoplethysmogram among various cardiovascular risk factors in middle-aged men.

The second derivative of the finger photoplethysmogram (SDPTG) has been used as a non-invasive examination for arterial stiffness. The present study sought to elucidate independent determinants of the SDPTG among various cardiovascular risk factors in middle-aged Japanese men. The SDPTG was obtained from the cuticle of the left-hand forefinger in 973 male workers (mean age: 44+/-6 years) during a medical checkup at a company. The SDPTG indices (b/a and d/a) were calculated from the height of the wave components. Multiple logistic regression analyses revealed that the independent determinants of an increased b/a (highest quartile of the b/a) were age (odds ratio [OR]: 1.12 per 1-year increase, 95% confidence interval [CI]: 1.09-1.15), hypertension (OR: 1.65, 95% CI: 1.03-2.65), dyslipidemia (OR: 1.51, 95% CI: 1.09-2.09), impaired fasting glucose/diabetes mellitus (OR: 2.43, 95% CI: 1.16-5.07), and a lack of regular exercise (OR: 2.00, 95% CI: 1.29-3.08). Similarly, independent determinants of a decreased d/a (lowest quartile of the d/a) were age (OR: 1.11 per 1-year increase, 95% CI: 1.08-1.14), hypertension (OR: 3.44, 95% CI: 2.20-5.38), and alcohol intake 6 or 7 days per week (OR: 2.70, 95% CI: 1.80-4.06). No independent association was observed between the SDPTG indices and blood leukocyte count or serum C-reactive protein levels. In conclusion, the SDPTG indices reflect arterial properties affected by several cardiovascular risk factors in middle-aged Japanese men. The association between inflammation and the SDPTG should be evaluated in further studies.     

Thoracoscopic resection of a solitary pulmonary lymphangioma: Report of a case

We present herein the rare case of a young man who was found to have a solitary tumor in the right upper lobe of his lung by a routine chest X-ray. The tumor was removed by thoracoscopic surgery, and pathological examinations confirmed the diagnosis of a primary lymphangioma of the lung. A brief review of the available literature on this extremely rare type of benign tumor follows the case report.     

A case of aneurysm of the inferior left ventricular wall

Aneurysms of the inferior left ventricular wall represent only a small fraction of all aneurysms that have been reported in surgical series. And in comparison to anterior left ventricular aneurysms, a comparatively higher percentage of reported inferior wall aneurysms was classified as false. A 73-year-old male was admitted for acute inferior myocardial infarction. Three weeks after admission, cardiac catheterization was carried out. Coronary arteriography revealed triple vessel disease and left ventriculography showed an aneurysm of the inferior left ventricular wall, whose feature near the mitral annulus was multiple fenestrations. Left ventricular aneurysmectomy and aortocoronary bypass grafting to the left anterior descending artery were simultaneously performed under cardiopulmonary bypass with moderate hypothermia. The pathological feature was a true aneurysm. The postoperative course was uneventful.     

A case of granulocyte-colony stimulating factor producing gastric cancer]

We report a case of granulocyte-colony stimulating factor producing gastric cancer with multiple liver metastases. A 68-year-old woman who complained of epigastralgia visited our hospital. Upper gastrointestinal endoscopic examination revealed a type-2 gastric cancer. The laboratory data at admission indicated leukocytosis (35,900/microl) and a high level of serum granulocyte-colony stimulating factor (61 pg/mg). Granulocyte-colony stimulating factor producing gastric cancer was diagnosed by immunohistochemistry of biopsy specimen. Since we detected multiple liver metastases, chemotherapy was performed. Granulocyte-colony stimulating factor-producing gastric cancer is relatively rare and we summarize previous reports.     

Ketamine infusion for control of pain in patients with advanced cancer

The effect of ketamine infusion to control the intractable pain which had not responded to ordinary procedures in 12 patients with advanced cancer were evaluated. Ketamine 250 mg or 500 mg in 500 ml of transfusion fluid with or without 10 to 20 mg of droperidol was administered intravenously at the rate of 3 to 20mg of ketamine per hour. The pain scores by VAS in most of the patients decreased significantly with an averaged value of 8.3 before the treatment to 1 during the procedure. The durations of this therapy lasted from over 6 hours to 48 days. Slight disorientation in one patient and drowsiness in 5 were seen during the infusion. No cardiovascular or respiratory complications were noted. These results indicate that ketamine infusion is a useful therapeutic procedure to treat cancer pain which resist ordinary pain therapies.     

Extraction of Potential Difficult-to-Manage Psychiatric Cases among Criminal Offenders: 5-Year Data from the Tokyo District Public Prosecutors Office

Abstract: In order to examine the characteristics of potential difficult-to-manage psychiatric cases, seven potential subgroups were extracted from the criminal offenders who were sent to the division of psychiatric diagnosis, Tokyo District Public Prosecutors Office for Pre-Prosecution Psychiatric Justice (PPPJ). The following criteria were used to select the potential subgroups: offenders who had experienced compulsory discharge from a mental hospital, those who had experienced Involuntary Admission to the mental hospital by the Prefectural Governor at least twice, those who had experienced admission to mental hospitals on more than 5 occasions, those who had been put on PPPJ previously for other criminal matters at least 3 times, those who had previously attempted suicide, and those who had committed homicide or arson. From the results of this study, it could be concluded that at least two types of "difficult-to-manage" psychiatric cases exist in the criminal offenders.     

Relation between Estrogen Receptor and Malignancy of Thyroid Cancer

The relationship between the histological grade of dedifferentiation of thyroid cancer and estrogen receptors (ER) was examined immunohistochemically. Thyroid cancers were from postmenopausal females of almost the same mean age (69-73 years old) and within the same period of time (1974–1983). ER immunoreactivity located in the nucleus of the epithelium was found in all 6 well differentiated papillary cancers, and 5 of them (83.3%) showed ER-immunoreactive (ER-IR) cells amounting to 20 or more per visual field (x 100) under a light microscope. Of the 6 cases of poorly differentiated papillary cancer, 5 (83.3%) had 1-19 ER-IR cells per visual field. ER-IR cells were negative in 5 out of 6 cases (83.3%) of anaplastic cancers. Thus, the number of ER-IR cells tended to decrease with the degree of atypism of thyroid cancer (P < 0.001).