-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice

-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD₅₀ in mice and conducted histopathological examinations. The 6-day LD₅₀, was found to be 199 mg/kg with 95% confidence limits of 126–314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.     

Criminal Responsibility in Amphetamine Psychosis

Abstract: Historical changes in forensic psychiatric evaluation on criminal responsibility and proceedings in psychopathological findings of amphetamine psychosis are reviewed at first. The classification of amphetamine related mental disorders are proposed in 6 types. Among them, the clinical characteristics and psychopathological features of “Anxiety-situational reaction type” (Fukushima) are described. According to some reasonable grounds, offenders diagnosed as anxiety-situational reaction type should be evaluated as diminished responsibility in place of irresponsibility. Finally, two cases of murder committed under the influence of amphetamine, are reported in detail.     

Application of an expandable metallic Z-type stent for stenosis of the left main bronchus following tuberculosis--a case report]

A 32-year-old man had been suffering from dyspnea on exertion and stridor, which were due to stenosis of the left main bronchus as a complication of bronchial tuberculosis. A three-connection stent, 1.2 cm in diameter and 4.5 cm in length was placed at the site of the bronchial stenosis. Dyspnea disappeared 2 days after the procedure, and the pulmonary function 3 weeks later showed considerable improvements in %FVC, FEV1 and MMF.     

POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION

1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt-resistant normotensives under strictly controlled metabolic ward conditions. 2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K-supplemented group (KG) than in the control group (CG). 3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG. 4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG. 5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.     

Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium.

We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats.

PURPOSE: This study investigated the effect of parathyroid hormone (1-34) [PTH(1-34)] on bone reactions after tibial placement of titanium screw implants into ovariectomized rats. MATERIALS AND METHODS: Twelve-week-old female Wistar rats were divided into 3 groups of 24. The first group (Sham group) was sham-operated; the second group (OVX group) was ovariectomized only; and the third group (PTH group) was subcutaneously administered 30 microg/kg PTH in the dorsal region 3 days per week starting the fourth week after ovariectomy until the end of the experiment. Titanium screw implants were placed in the proximal metaphysis of the tibia of all 3 groups at 168 days after surgery. The animals were killed 7, 14, 28, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained using a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact. RESULTS: When PTH administration was started 21 days after ovariectomy, the volume density of bone around implants in the PTH group was almost the same as that of the Sham group throughout the entire observation period. This finding suggests that not only can intermittent human PTH(1-34) administration prevent resorption of newly generated trabeculae around an implant but also it can aid in the recovery of bone volume lost due to ovariectomy. CONCLUSION: When dental implants are applied to jaw bone showing trabecular bone loss, it may be possible to increase bone density around an implant by intermittent human PTH(1-34) administration and thereby improve clinical results.     

A case of autoimmune pancreatitis complicated with immune thrombocytopenia]

A 80-year old man was referred to our hospital because of an elevation of serum amylase level. Diffuse enlargement of the pancreas was detected by abdominal computed tomography, and also diffuse narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. The serum level of IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet-associated IgG, antiplatelet antibody and antinuclear antibody in serum were positive. The levels of serum complements were low. From all these findings the patient was diagnosed as autoimmune pancreatitis complicated with immune thrombocytopenia. The treatment with prednisolone was started, which was effective on each disease. The medication was suspended a year ago, and so far there is no data suggesting the recurrence of autoimmune pancreatitis or immune thrombocytopenia.