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.     

Cibenzoline-induced respiratory muscular paralysis in a hemodialysis patient

A 69-year-old man was admitted to our kidney center with endstage renal failure. We started intermittent peritoneal dialysis immediately because of severe azotemia, hyperkalemia, and metabolic acidosis. Two weeks after admission, he developed uremic pericarditis with frequent ventricular premature contractions and supraventricular premature contractions. The intermittent peritoneal dialysis was then replaced by intensive hemodialysis, and oral administration of 300 mg/d of cibenzoline was started. Four days later, he developed thirst, weakness, and dyspnea due to respiratory muscular paralysis. We initiated respiratory support with a respirator because analysis of his blood gases revealed marked hypercapnia and hypoxia. He also developed hypoglycemia and prolonged PQ and QRS intervals on the electrocardiogram, which we believed were due to cibenzoline intoxication; we discontinued the cibenzoline immediately. All symptoms improved, and he was extubated 5 days later. After 2 months, his pericardial effusion disappeared. He now continues maintenance hemodialysis as an outpatient. We suspect that the cibenzoline induced the respiratory muscular paralysis for 2 reasons: 1) the patient experienced the respiratory muscular paralysis, at the same time he also experienced thirst, weakness, hypoglycemia, and prolonged PQ and QRS intervals on electrocardiogram, and all of these symptoms improved after the discontinuation of cibenzoline, and 2) his plasma concentration of cibenzoline became remarkably elevated, to 20 times above the standard therapeutic level. This patient's clinical course indicates that hemodialysis might be superior to intermittent peritoneal dialysis for treatment of cibenzoline intoxication.     

Experimental studies of photo radiation therapy on neuroblastoma

A combination of Photo Radiation Therapy (PRT) using Argon-Dye Laser with hematoporphyrin derivatives (HpD) was used experimentally on a cytogenetically highly malignant neuroblastoma xenograft, which exhibited a homogeneously staining region and caused DNA amplifications in chromosomes. The tumor tissue was treated with 500 joules/cm2 of laser. The dosage of HpD was 50 mg per kg body weight. Necrosis of over 50% of the tumor was observed in half the specimens. Swollen cytoplasmic organelles and ruptured cell and nuclear membranes were observed by electron microscopy after PRT. PRT may be used with other treatment modalities for the removal of residual and metastatic tumors.     

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.     

Disposition characteristics of macromolecules in the perfused tissue-isolated tumor preparation.

Disposition characteristics of model macromolecules with different physicochemical characteristics and macromolecular prodrugs of mitomycin C, namely mitomycin C-dextran conjugates, were studied in tissue-isolated tumor preparations of Walker 256 carcinoma with the use of a single-pass vascular perfusion technique. In constant infusion experiments, all radiolabeled macromolecules accumulated in the tumor tissue, but the degree and pattern of distribution greatly varied, depending on their electric charges. Positively charged macromolecules were markedly accumulated compared with those that were neutral or negatively charged. In addition, their concentrations were significantly higher in viable than in necrotic regions, while neutral and negative compounds were distributed in necrotic rather than in viable regions. Pharmacokinetic analysis of tissue concentration-time courses of positively charged diethylaminoethyl and neutral dextrans showed that their movement occurred by convective fluid flow, and that high tissue accumulation of positively charged macromolecules could be explained by strong binding due to electrostatic interaction. For neutral and anionic macromolecules with negligible affinity to the tissue, it was suggested that the final concentration gradient between the viable and necrotic regions was decided by their tissue fluid content. Thus, the present study revealed the basic disposition characteristics of macromolecules in tumor tissue relative to their physicochemical properties.     

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.