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.     

Extracellular pH in the brain during ischemia: relationship to the severity of lactic acidosis

On the basis of data showing a bimodal distribution of values for extracellular pH (pHe), and a discontinuous delta PCO2/delta lactate relationship, Kraig et al. (1986) proposed that H+ is grossly compartmentalized between neurons and glia in the ischemic brain. We measured delta pHe during ischemia, varying ischemic lactate contents between 9 and 38 mmol kg-1. No bimodal distribution was found, but delta pHe varied linearly with lactate content. Because we have also failed to record a discontinuous delta PCO2/delta lactate relationship, we conclude that major compartmentation of H+ does not occur during ischemia.     

Validation of silver-stained nucleolar organizer regions for evaluation of invasive character of urinary bladder carcinoma in rats and mice

A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silverstained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P<0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.     

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 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.     

The effect of megestrol acetate on interleukin-1 activity.

The current study investigates the effect of megestrol acetate, a synthetic progestin, on the activity of interleukin-1. Murine thymocytes were suspended in vitro and stimulated with varying concentrations of interleukin-1. [3H]Thymidine uptake was observed as an index of thymocyte proliferation. A dose-dependent increase in [3H]thymidine uptake was observed with increasing concentrations of interleukin-1. When megestrol acetate was added to the solution, a marked suppressive effect was observed. Higher doses of megestrol acetate had a greater suppressive effect on thymocyte proliferation. Additional investigation is required to further delineate the potential systemic effects of megestrol acetate.     

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.     

A case of primary hypothyroidism with repeated episodes of respiratory failure

A case of repeated episodes of hypoventilatory respiratory failure accompanied with primary hypothyroidism was reported. A 76-year-old woman was admitted to our hospital due to both disturbance of consciousness and respiratory failure. A diagnosis of primary hypothyroidism complicated with hypoventilatory respiratory failure deterioration due to respiratory infection was made. Supplemental therapy of thyroid hormones improved her general condition, but respiratory failure recurred after interruption of a replacement drug. Cases of unexplained respiratory failure should be differentiated from respiratory failure induced by hypothyroidism.