Alternations in the maternal behavior of rats rearing malnourished offspring

Investigations of maternal behavior of mothers fed a low-protein diet indicated deficits in retrieval and in the rate of nest-building. In addition, they indicated a concomitant increase in time spent with young when assessed during periods not associated with the retrieval/nest-building test session. The adrenalectomized mother, another case that produces growth-stunted progeny, was compared with both low-protein and control mothers for maternal behavior. Unlike the low-protein mother, the adrenalectomized mother did not exhibit retrieval or nest-building deficits; however, the adrenalectomized mother did display an increase in time spent with young. These data suggest that although deficits in retrieval and nest-building can be attributed to the nutritional condition of the mother, the stimulus characteristics of the malnourished pup are important in eliciting the increased time spent with the litter.     

Dextran Sulphate Osteopathy in Parathyroidectomised Rats

The synthetic heparin substitute dextran sulphate induces osteoporosis after prolonged administration to experimental animals. The possibility that this is brought about indirectly by hypocalcaemia and secondary hyperparathyroidism as a result of the binding of ionised calcium by dextran sulphate has been studied in rats.Twenty-four rats were given 25 mg. per kg. per day of sodium dextran sulphate for periods up to 11 weeks. Sixteen were given the same amount of dextran sulphate but were previously parathyroidectomised. Two control groups comprised 17 intact and 15 parathyroidectomised rats, respectively. The limb bones were examined histologically and their sizes and growth rates measured from radiographs and by tetracycline labelling. The parathyroid glands from intact control and dextran sulphate treated rats were compared histologically and the serum calcium estimated in each animal.All rats given dextran sulphate showed thinning of the metaphyseal cortical bone as a result of impaired endochondral ossification. Parathyroidectomised rats continued to grow and the lengths of their limb bones were unaffected. Parathyroidectomy had no influence on the occurrence or severity of bone changes attributed to dextran sulphate. Furthermore, serum calcium remained normal and there was no evidence of parathyroid hyperplasia in the intact dextran sulphate treated rats.It is concluded that dextran sulphate induces osteoporosis in growing animals by interfering with endochondral ossification and does not induce hypocalcaemia and secondary hyperparathyroidism.     

High-dose radioimmunotherapy combined with fixed, low-dose paclitaxel in metastatic prostate and breast cancer by using a MUC-1 monoclonal antibody, m170, linked to indium-111/yttrium-90 via a cathepsin cleavable linker with cyclosporine to prevent human anti-mouse antibody.

PURPOSE: Although radioimmunotherapy alone is effective in lymphoma, its application to solid tumors will likely require a combined modality approach. In these phase I studies, paclitaxel was combined with radioimmunotherapy in patients with metastatic hormone-refractory prostate cancer or advanced breast cancer. EXPERIMENTAL DESIGN: Patients were imaged with indium-111 (111In)-1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid-peptide-m170. One week later, yttrium-90 (90Y)-m170 was infused (12 mCi/m2 for prostate cancer and 22 mCi/m2 for breast cancer). Initial cohorts received radioimmunotherapy alone. Subsequent cohorts received radioimmunotherapy followed 48 hours later by paclitaxel (75 mg/m2). Cyclosporine was given to prevent development of human anti-mouse antibody. RESULTS: Bone and soft tissue metastases were targeted by 111In-m170 in 15 of the 16 patients imaged. Three prostate cancer patients treated with radioimmunotherapy alone had no grade 3 or 4 toxicity. With radioimmunotherapy and paclitaxel, two of three prostate cancer patients developed transient grade 4 neutropenia. Four breast cancer patients treated with radioimmunotherapy alone had grade 3 or 4 myelosuppression. With radioimmunotherapy and paclitaxel, both breast cancer patients developed grade 4 neutropenia. Three breast cancer patients required infusion of previously harvested peripheral blood stem cells because of neutropenic fever or bleeding. One patient in this trial developed human anti-mouse antibody in contrast to 12 of 17 patients in a prior trial using m170-radioimmunotherapy without cyclosporine. CONCLUSIONS: 111In/90Y-m170 targets prostate and breast cancer and can be combined with paclitaxel with toxicity limited to marrow suppression at the dose levels above. The maximum tolerated dose of radioimmunotherapy and fixed-dose paclitaxel with peripheral blood stem cell support has not been reached. Cyclosporine is effective in preventing human anti-mouse antibody, suggesting the feasibility of multidose, "fractionated" therapy that could enhance clinical response.     

Dexamethasone normalizes brain tumor hemodynamics as indicated by dynamic susceptibility contrast MRI perfusion parameters

The purpose of this study is to demonstrate the utility of dynamic susceptibility contrast (DSC) MRI-derived perfusion parameters to characterize the hemodynamic effects of dexamethasone in a 9L gliosarcoma tumor model. Twenty-four rats underwent intracerebral inoculation with 9L tumor cells. Fifteen were treated with a total of 3mg/kg of dexamethasone on days 10-14 post-inoculation, while the remaining 9 rats served as controls. Fourteen days post-inoculation, MRI images, sensitive to total and micro-vascular cerebral blood flow (CBF), mean transit time (MTT), and intravoxel transit time distributions (TTD)s were obtained using a simultaneous gradient-echo(GE)/spin-echo(SE) DSC-MRI method. Dexamethasone-treated animals had a microvascular (SE) tumor CBF that was 45.9% higher (p = 0.0008) and a MTT that was 47.8% lower (p = 0.0005) than untreated animals. With treatment, there was a non-significant 91.3% increase in total (GE) vascular CBF (p = 0.35), and a significant decrease in MTT (49.1%, p = 0.02). The total vascular and microvascular TTDs from the treated tumors were similar to normal brain, unlike the TTDs in the untreated tumors. These findings demonstrate that DSC-MRI perfusion methods can be used to non-invasively detect the morphological and functional changes in tumor vasculature that occur in response to dexamethasone treatment.