Role of pentoxifylline in preventing radiation damage to epiphyseal growth plate chondrocytes.

Radiation therapy plays an important role as part of multimodality treatment for a number of childhood malignancies. The damaging effects of radiation on bone formation in children have been well documented. Recent work suggests that the postirradiation increase in cytosolic calcium is probably responsible for the deleterious effects of radiation on growth plate chondrocytes because it causes a specific suppression of the mitogen PTHrP. Using an in vitro model of avian growth plate chondrocytes, this study demonstrates that pentoxifylline is effective in increasing basal PTHrP mRNA levels and partially preventing the radiation-induced decrease in PTHrP mRNA. This effect of pentoxifylline is probably due to its ability to lower basal levels of cytosolic calcium and the radiation-induced increase in cytosolic calcium in chondrocytes. Pentoxifylline also prevented the radiation-induced decreases in [3H]thymidine uptake and BCL2 and PTHrP receptor mRNA levels in chondrocytes. The effects of pentoxifylline appear to be specific for the PTHrP signaling pathway because it did not alter basal TGFB mRNA levels or TGFB mRNA expression in irradiated chondrocytes. The results of the current study suggest that by decreasing basal cytosolic calcium levels and curtailing the radiation-induced increase in cytosolic calcium levels in chondrocytes, pentoxifylline is able to sustain PTHrP signaling in chondrocytes and maintains the proliferative signal that is necessary to prevent chondrocytes from undergoing apoptosis.     

Production of isomaltooligosaccharides by a-glucosidase immobilized in chitosan beads and by polyethyleneimine-glutaraldehyde treated mycelia of Aspergillus carbonarious

Partially purified a-glucosidase from Aspergillus carbonarious, immobilized on glutaraldehyde-activated chitosan beads in a packed bed reactor, produced isomaltooligosaccharides at a yield of 60% (w/w) using 30% (w/v) maltose solution. Using intact mycelia attached with polyethyleneimine-glutaraldehyde, produced isomaltooligosaccharides at a yield of 46% (w/w) using 30% (w/v) maltose solution. Batchwise reaction stabilities were improved for chitosan beads immobilized enzyme and polyethyleneimine-glutaraldehyde treated mycelia as compared to mycelia without any treatment.     

Zinc coadministration attenuates melatonin’s effect on nitric oxide production in mice

Both melatonin (MEL) and zinc (Zn) are considered beneficial for anti-immunosenescence. MEL’s effects on immune functions are partly attributed to an interaction with Zn. However, the augmentation of or interference with MEL’s effects by coadministration of Zn remains unclear. In this study, adult older mice received either MEL (10 μg/mL), Zn (22 μg/mL), MEL+Zn, or null supplementation from drinking water for 3 mo. The results showed that treated mice, irrespective of the type of added chemicals, had higher body-weight gain and body-fat content than control mice. MEL- and Zn-treated mice also had increased serum free fatty acid levels. In addition, the MEL group had decreased serum NO_X (nitrite+nitrate) values. Serum tumor necrosis factor-alpha levels were increased, although nonsignificantly, in mice that received either MEL or Zn supplementation. However, the differences described were not retained in the mice that received MEL+Zn treatment. We conclude that a high-dose Zn coadministration might exert negative influences on MEL’s regulatory effects, at least on nitric oxide production.     

Dominant lethal assay of some hair-dye components in random-bred male rats.

Male rats were exposed to maximally tolerated doses of 5 hair-dye components in a dominant lethal test. Each component was tested at 3 dosage levels with 15 random-bred male rats per level. The highest dose, selected on the basis of subacute toxicity testing, generally reduced weight gains without being lethal. Freshly prepared solutions were injected i.p. at 1 ml/kg 3 times a week for 10 weeks. Rats injected with dimethylsulfoxide and triethylenemelamine served as solvent and positive controls, respectively. A majority of rats survived the treatment at the levels tested and were mated to two virgin females each per week for 2 weeks. The females were sacrificed at midterm of pregnancy and examined for live and dead implants. Dominant lethality was evaluated on the basis of 4 criteria: dead implants per pregnant female, dead implants per total implants, proportion of females with one or more dead implants, and proportion of females with two or more dead implants. 2-Nitro-p-phenylenediamine, 2,4-diaminoanisole sulfate and 2,5-diaminoanisole sulfate produced negative responses, whereas m-phenylenediamine and 4-nitro-o-phenylenediamine induced weak dominant lethality in the first trial. On retesting these weakly positive components, both m-phenylenediamine and 4-nitro-o-phenylenediamine produced negative responses.     

Chemotherapy with doxorubicin in progressive medullary and thyroid carcinoma of the follicular epithelium.

Twenty-two patients (mean age 61) with metastasizing, progressive, nonradioiodine-accumulating thyroid carcinoma of the follicular epithelium were treated with doxorubicin between 2000 and 2005. Tumors were histologically classified as follicular in 15 patients (68%) and papillary in 7 patients (32%). In addition, nine patients (mean age 51 years) with medullary thyroid carcinoma were treated with doxorubicin between 1997 and 2005. Treatment consisted of doxorubicin: either 8 cycles of 15 mg/m2 weekly or 3 cycles of 60 mg/m2 every 3 weeks, repeated once, depending on response and side effects. The effect of therapy was evaluated by radiographic imaging, [18F] FDG-PET, and bone scans. In patients with papillary or follicular thyroid carcinoma, 5% had a partial regression over 6 months, 42% had stable disease for a median of 7 months (range: 1-22), and 53% had continuous progression established over 5 months (range: 1-11). Three patients died before completing chemotherapy. In patients with medullary thyroid carcinoma, 11% had a partial regression over 6 months followed by stable disease for 3 months, 11% had stable disease over 7 months, and 79% demonstrated progressive disease established over 5 months (range: 2-12). Doxorubicin can be a valid chemotherapy option, especially for advanced or metastatic thyroid carcinoma of the follicular epithelium.