Heterotransplantation of the cultured cell from a human giant cell tumour of bone

Summary We have transplanted cultured cells derived from a human giant cell tumour of bone (G-1 cell) into immunologically suppressed mice. The resulting growths were morphologically and cytokinetically analyzed. We have obtained information on the cytokinetic influences of anti-cancer agents on heterotransplanted tumours using the double labelling method.Tumour formation was noted in 56 out of 76 mice, i.e. 76%. In 3 mice which had been kept under observation the large tumours led to death.The heterotransplanted tumours of G-1 cells had morphologically malignant and non-epithelial characteristics. The cells appeared to have undergone malignant change during their long period of cultivation.Using the double labelling method, 5-FU was found to prolong the DNA synthetic time and decrease the cell birth rate of G-1 cells in vivo. Accordingly, 5-FU is the most effective anti-cancer agent to G-1 cells.In order to improve the prognosis in a malignant bone tumour the most effective anti-cancer agent should be determined by testing on a heterotransplanted tumour derived from the patient.

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Résumé Les auteurs ont greffé des cellules cultivées à partir d'une tumeur osseuse à cellules géantes humaine (cellule G-1) sur des souris ayant subi une suppression immunitaire. Les tumeurs résultantes ont été analysées sur le plan morphologique et cytocinétique. Grâce à la technique du double marquage, on a obtenu des informations concernant les influences cytocinétiques des agents anticancéreux sur les tumeurs hétérotransplantées.Des tumeurs se sont développées chez 56 souris sur 76, soit 76%. Chez trois animaux soumis à une observation prolongée, on a constaté que les volumineuses tumeurs qui se sont formées ont entraîné la mort.Les tumeurs hétérotransplantées des cellules G-1 étaient morphologiquement malignes et non épithéliales. Les cellules ont apparemment subi une transformation maligne pendant leur longue période de culture.A l'aide du double marquage on a trouvé que le 5-fluoro-uracile prolongeait le temps de synthèse de l'ADN tandis qu'il diminuait le taux de division des cellules G-1 in vitro. Le 5-fluoro-uracile est donc l'agent anticancéreux le plus efficace à l'égard des cellules G-1.Pour améliorer le pronostic d'une tumeur osseuse maligne, on devrait déterminer l'agent anticancéreux le plus efficace en le testant sur une tumeur hétérotransplantée dérivée du malade.

     

Case of combined adrenal cortical adenoma and myelolipoma

We report a case of myelolipoma 10 mm in size within a functional cortical adenoma that was 33 x 22 x 17 mm in size. A 29-year-old woman was referred to hospital for transient hypertension. A right adrenal tumor was detected by computed tomography (CT) scan and magnetic resonance imaging (MRI). Her cortisol levels indicated a loss of the normal diurnal pattern, and urinary 17-hydroxycorticosteroids was elevated. She underwent a right adrenalectomy under the diagnosis of adrenal adenoma with Cushing's syndrome. The tumor was fairly well encapsulated by a thin layer of connective tissue. The major tumor portion was composed of two distinct cell types, clear cells and eosinophilic cells, arranged in an alveolar structure. These findings were representative of cortical adenoma. The adrenal cortical adenoma centrally included well-demarcated adipose tissue admixed with scattered islands of myelopoietic elements: erythroblasts, myeloid cell series and lymphocytic cells, which was eventually recognized as myelolipoma. Recently, adrenal myelolipoma has commonly been found because of the ease of detecting it as an incidentaloma by CT scan or MRI. However, the present adrenal myelolipoma case is uncommon because it is combined with a functioning cortical adenoma. Only six similar cases have previously been reported in English and Japanese publications. Furthermore, in the present case, the myelolipoma formed a tumor nodule, and to our knowledge, this is the first reported case of a radiographically recognizable tumor nodule. We discuss the etiology of myelolipoma and suggest that myelolipoma can develop in the course of endocrine hyperfunction.     

Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigs

An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A(2) (TXA(2)) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA(2) synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB(2), a stable metabolite of TXA(2), and the time-course of plasma TXB(2) was similar to that of the decreased partial oxygen pressure of arterial blood (Pao(2)) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao(2) and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB(2 )and its weight ratio to 6-keto prostaglandin F(1alpha) in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao(2), post treatment showed little effect. We suggest that TXA(2) participated in the oleic acid lung injury, as an "early phase" mediator, and rapidly-acting TXA(2) synthase inhibitors were effective in the prevention of acute lung injury.     

FR171456, a novel cholesterol synthesis inhibitor produced by Sporormiella minima No. 15604. I. Taxonomy, fermentation, isolation, physico-chemical properties

FR171456 and FR173945, novel and potent cholesterol synthesis inhibitors, have been isolated from the fermentation broth of a fungal strain No. 15604. This strain was identified Sporormiella minima from its mycological characteristics. FR171456 and FR173945 strongly inhibited cholesterol synthesis in human hepatoma cell line Hep G2. These compounds also have in vitro antifungal activity against Candida albicans and Aspergillus fumigatus.     

Pharmacokinetics of roxatidine acetate in patients with chronic liver disease

BACKGROUND AND AIM: Patients with liver disease are prone to develop peptic ulceration and often receive H(2)-receptor antagonists. Therefore, it is important to clarify whether the pharmacokinetics of H(2)-receptor antagonists is affected by hepatic function. However, pharmacokinetics of a new H(2)-receptor antagonist, roxatidine acetate, in chronic liver disease has not been well known. In this study, we analyzed the pharmacokinetics of roxatidine in patients with liver disease. METHODS: Blood samples were obtained from 11 patients with chronic hepatitis, 11 patients with cirrhosis and six healthy subjects. Under fasting conditions, 75 mg of roxatidine acetate was administered orally, and plasma roxatidine levels were determined sequentially from 3 to 12 h. Relationships between pharmacokinetic variables and each parameter related to hepatic functions were also investigated. RESULTS: There was no difference in the pharmacokinetic variables and serum levels of roxatidine between chronic hepatitis and healthy controls. In contrast, in cirrhosis, serum roxatidine levels were significantly higher than those in chronic hepatitis and normal control. Half-life, the area under the plasma concentration-time curve and clearance in cirrhosis were also significantly longer, bigger and smaller than those in chronic hepatitis and healthy controls, respectively. The half-life became longer and the clearance became smaller in parallel with the progression of liver disease. Serum levels of hyaluronate and gamma-glutamyl transpeptidase showed a good correlation with half-life, clearance and elimination rate. A good correlation between creatinine clearance and elimination rate was found. CONCLUSION: Pharmacokinetics of roxatidine acetate is affected by hepatic function, and the dosage of roxatidine acetate for patients with liver disease, especially cirrhosis, should be modified.     

Effects of phytosterols in diacylglycerol as part of diet therapy on hyperlipidemia in children

BACKGROUND: The incidence of hyperlipidemia in children is increasing in Japan, but drug therapy for such children is limited. The ingestion of 4% phytosterols-containing diacylglycerol (PS/DAG) decreases serum total cholesterol and low density lipoprotein cholesterol (LDL-C) concentrations in adults. In the present study, we examined the effect of PS/DAG as part of a diet therapy in pediatric patients with hyperlipidemia. METHODS: Pediatric patients with hyperlipidemia with > or =5.18mmol (200 mg/dL) serum total cholesterol and/or >or =1.70mmol (150 mg/dL) triglycerides (N=22) ingested bread containing PS/DAG (total daily intake, 10g) for 6 months. Blood chemistry was examined prior to and 2, 4, 6 months after the initiation of ingestion, and 4 months after the ingestion period. RESULTS: No significant differences in energy intake or cholesterol intake during the study period were found. After 4 months of ingestion of PS/DAG, LDL-C, lipoprotein(a) [ Lp(a)], free fatty acids and total ketone bodies decreased significantly. In seven patients with familial hypercholesterolemia, total cholesterol and remnant-like lipoprotein particles (RLP)-cholesterol also significantly decreased in addition to LDL-C and Lp(a). CONCLUSIONS: PS/DAG improves serum lipid metabolism in pediatric patients with hyperlipidemia for whom drug therapy is limited, suggesting that PS/DAG may reduce the risk of developing various diseases induced by hyperlipidemia.     

Metabolism of diacylglycerol in humans

Obesity resides upstream of the constituents of metabolic syndromes such as diabetes, hypertension, hyperlipidemia, and arteriosclerosis. Postprandial hyperlipidemia is also implicated in atherogenesis. Therefore, factors that influence the body adiposity and the magnitude of postprandial hyperlipidemia have been intensively investigated. Diacylglycerol (DAG) oil, which is defined to contain DAG 80% (w/w) or greater in the present presentation, is an edible oil with similar taste and usability compared with conventional edible oil rich in TAG. Safety of DAG has been widely evaluated and listed as a GRAS (Generally Recognized as Safe) substance by US FDA. The aim of this review was to summarize the metabolism and nutritional functions of DAG based on the data from scientific journals and conference publications. Effect of DAG ingestion on postprandial elevations of serum lipids was investigated in several dosages, food formula, and in subjects in various conditions. Postprandial triglyceride in serum and the chylomicron fraction are significantly smaller after DAG consumption compared with TAG with a similar fatty acid composition in healthy subjects, and was remarkably reduced in subjects with insulin resistance. Long-term DAG ingestion in controlled diet or free-living condition significantly decreased body adiposity and improved type II diabetic complications. A single dose DAG consumption significantly increased fat oxidation as compared to eucaloric TAG ingestion. DAG oil consumption might be beneficial in reducing the risk factors for lifestyle-related diseases such as obesity, visceral obesity, postprandial hyperlipidemia, insulin resistance, and atherosclerosis.     

Elderly people living in Florianópolis: self-perception of oral health conditions and use of dental services

This paper is based on the Florianopolis Municipality Senior Citizen's Profile (2004) built up on the questionnaire in the Brazil Old Age Schedule (BOAS), applied to 875 elderly people. The data highlighted by this cross-section are related to the self-perception of the respondents of their oral health condition and use of dental services, which were then associated with the socio-demographic variables. The discrepancy between oral health data perception and actual oral health status - such as high percentages of missing teeth and dentures - discloses the way in which the elderly perceive this aspect of their own health. The state of their teeth was associated only with family income. Recent visits to dentists were associated with the need for dentures and medical referrals. This study indicates a need for public policies focused specifically on the oral health of the elderly, in addition to ways of promoting health and wellness for all during the irreversible aging process.