Effect of arachidonic acid metabolites on bone resorption by isolated rat osteoclasts

Arachidonic acid metabolites (eicosanoids) have major effects on bone but their role is unclear. Many are known to stimulate bone resorption in organ culture, but paradoxically, previous work has suggested that at least some of them act as direct inhibitors of osteoclastic function. In an attempt to clarify the role of eicosanoids in bone physiology, we have defined the duration of action and relative potencies of prostaglandin (PG) E1 and E2 and have extended the range of eicosanoids tested on isolated osteoclasts. We have found that PGE1 and PGE2 inhibited bone resorption by isolated osteoclasts for at least 6 h. Inhibition was followed by recovery to control, not supranormal levels. Bone resorption was inhibited in the range 10(-5)-10(-9) M for PGE1 and PGE2, and the rank order as resorption inhibitors was PGE1 greater than 6-keto PGE1 greater than PGE2 greater than PGA2 greater than PGB2. None of the products of lipoxygenase metabolism showed a significant direct effect. The effects of PGE1 and PGE2 were not antagonistic. Prostaglandin production does not seem to be implicated as a second messenger for the action of calcitonin. Although inhibition of osteoclasts by PGs was less prolonged than that observed in the presence of calcitonin, the sensitivity of osteoclasts to inhibition by PGs, and the duration of the effect without subsequent direct stimulation, suggests that inhibition of osteoclastic resorption is a major physiological role of PG production in bone.     

Localization of 3H-proline, 35S-sulfate and 3H-glucosamine in rat cornea following epithelial removal: epithelio-stromal interaction

Localization of 3H-proline, 35S-sulfate and 3H-glucosamine was studied by autoradiography in the rat cornea following the removal of the epithelium. The three labeling chemicals were injected into the anterior chamber of rats, one chemical in each rat, 24 hours after the removal of the epithelium. Animals were sacrificed at various intervals up to 7 days after the injection. The silver grains of 35S-sulfate incorporated into the re-covered epithelium gradually shifted into the stroma. On the other hand, the 3H-glucosamine tended to move toward the epithelial cell membrane and the superficial layer of the epithelium. The 3H-proline incorporated in the epithelium remained in the cells without movement. These results suggest that the 35S-sulfate in the epithelium shifted into the stroma as 35S-phosphoadenosine-phosphosulfate [35S-PAPS] before sulfation of glycoconjugates occurred in the epithelium. A large amount of 3H-glucosamine was utilized as a component of low-sulfated glycoconjugates in the epithelial cell membrane and other cell-coating substances.     

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.     

Protection of photosensitized rats against long ultraviolet radiation by topical application of compounds with structures similar to that of dihydroxyacetone

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.     

Clinical phase I study of T-2588

A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses.     

271. Tuberkulose nach lebertransplantation

Zusammenfassung Bei einem 55jährigen Mann wurde 7 Monate nach orthotoper Lebertransplantation eine Lungentuberkulose diagnostiziert. Die tuberculostatische Therapie erfolgte mit Isoniazid (3 x 0,2 g/Wo) und Ethambutol (1,6 g/d) über 11 Monate. Nach 3 Monaten waren keine Mycobakte rien mehr nachweisbar, und der Patient ist im 3. Jahr nach Transplantation ohne Zeichen einer aktiven Tuberkulose in gutem Gesundheitszustand bei guter Transplantatfunktion. Die Tuberculostatica-Dosierung sollte je nach Metabolisierungsleistung des Transplantats reduziert werden. Bei Beachtung dieses Kardinalpunktes könnte eine Tuberkulose nach Lebertransplantation erfolgreich behandelt werden.     

A case report of inflammatory breast cancer effectively treated with cis-platinum

A 50-year-old woman with bilateral inflammatory breast cancer (T4, N1b, M1, Stage IV) underwent right extended radical mastectomy and left modified radical mastectomy following pre-operative administration of carcinostatics (ADM, 5-FU) and irradiation. However, tumor recurrence was observed at the skin and right pleural cavity after the operation. Adriamycin-containing combination chemotherapy and radiation therapy were performed, but no significant response was obtained. CDDP was then administered intravenously at a daily dose of 62.5 mg/m2 at intervals of 60 days. The pleural effusion disappeared and the extent of skin metastasis was reduced, resulting in partial response which lasted for 90 days. The serum CEA level decreased from 13.1 ng/ml to 2.3 ng/ml. As the side effects of this therapy, slight nausea, vomiting and general fatigue were observed. This result suggested that CDDP is an effective drug for inflammatory breast cancer.     

Molecular genetic diagnosis in X chromosome-linked retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common hereditary dystrophic disease of the retina. About 10% of the affected families show the X-linked trait. The close link observed between the gene locus (RP2) and a polymorphic DNA marker (DXS7) on the proximal short arm of the X-chromosome permits an indirect genotype diagnosis and can be helpful in carrier detection and genetic counseling. A case is presented in which the carrier risk of a female consultant dropped from 50% a priori to less than 2% by the use of clinical findings and DNA analysis.