- Methadone, a synthetic opioid agonist, is commonly used for the treatment of heroin dependence. Depending on how alcohol addiction is defined, rates of alcoholism vary among those attending methadone maintenance treatment (MMT) programmes. Most of the current literature has shown that alcohol consumption increases during medium- or long-term MMT. However, up to now, no data have been reported on changes in alcohol intake among a population of heroin addicts with no alcohol-dependence diagnosis after short-term methadone administration. Thus, the aim of our study was to investigate alcohol consumption changes in a population of non-alcoholic heroin addicts during the first 4 weeks of a treatment programme (TP). The TP consisted of either MMT or non-methadone maintenance treatment (N-MMT) with a minimum duration of 1 year. A total of 359 heroin-addicted out-patients [274 males (76.3%)], all of whom met DSM-IV criteria, were enrolled in the study, over a period of 4 months. Out of these 359 patients, 32 subjects (8.9%) dropped out, whereas 327 subjects (91.1%; 249 males) continued the TP [105 (32.1%; 78 males) in the MMT group and 222 (67.9%; 171 males) in the N-MMT group]. A significant reduction in daily alcohol intake was observed in the MMT group, but not in the N-MMT group after the first 4 weeks of the TP. The results of the present study suggest a possible effect of short-term methadone administration in reducing alcohol consumption in a population of non-alcoholic heroin-addicted patients.

Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of 10B-boronated compounds by some tumors, followed by irradiation with an appropriate neutron beam. The radioactive boron originated (11B) decays releasing 7Li, gamma rays and alpha particles, and these latter will destroy the tumor. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. In in vitro studies, the uptake of p-10borophenylalanine (BPA) by the UTC cell line ARO, primary cultures of normal bovine thyroid cells (BT), and human follicular adenoma (FA) thyroid was studied. No difference in BPA uptake was observed between proliferating and quiescent ARO cells. The uptake by quiescent ARO, BT, and FA showed that the ARO/BT and ARO/FA ratios were 4 and 5, respectively (p < 0.001). In in vivo studies, ARO cells were transplanted into the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg body weight) was injected intraperitoneally. The animals were sacrificed between 30 and 150 minutes after the injection. With 350 mg, tumor uptake was highest after 60 minutes and the tumor/normal thyroid and tumor/blood ratios were 3 and 5, respectively. When 600 mg/kg body weight BPA were administered, after 90 minutes the tumor/blood, tumor/normal thyroid, and tumor/distal skin ratios for 10B concentrations per gram of tissue were approximately 3, showing a selective uptake by the tumor. The present experimental results open the possibility of applying BNCT for the treatment of UTC.

Undifferentiated thyroid carcinoma (UTC) is a rapidly growing, highly invasive malignant tumor that currently lacks any effective treatment. Boron neutron capture therapy (BNCT) has been investigated recently for some types of tumors including glioblastoma multiforme and malignant melanoma. In previous studies we have shown the selective uptake of p-boronophenylalanine (BPA) by undifferentiated thyroid cancer cells in vitro and in vivo, as well as the histologic cure of 50% of the nude mice transplanted with human UTC cells when treated with BPA and an appropriate neutron beam. The present studies were performed to further optimize this treatment through the investigation of a boronated porphyrin, both alone and in combination with BPA. In vitro studies with cells in culture showed that BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha,beta-dihydroxyethyl)-deutero-porphyrin IX) is localized intracellularly, with a highest concentration in the 11500g (mitochondrial-enriched pellet) fraction. When BOPP was administered alone to NIH nude mice transplanted with UTC human cells, no significant tumor uptake or selectivity in our in vivo model was observed. In contrast, when BOPP was injected 5-7 days before BPA and the animals were sacrificed 60 min after administration of BPA, a significant increase in boron uptake by the tumor was found (38-45 ppm with both compounds vs 20 ppm with BPA alone). On day 5 the tissue boron selectivity ratios were tumor/blood approximately 3.8 and tumor/distal skin approximately 1.8. Other important ratios were tumor/thyroid approximately 6.6 and tumor/lung approximately 2.9. These results open the possibility of improving the efficacy of BNCT for the treatment of this so far "orphan" tumor.

No abstract

Differentiated thyroid cancer and hyperthyroidism are treated with radioiodine. However, when the radioisotope dose exceeds certain limits, the patient must be hospitalized to avoid contact with people that would otherwise be exposed to radiation. It would be desirable to obtain a similar therapeutic effect using lower radioiodine doses. Radiosensitizers can be utilized for this purpose. Nicotinamide (NA) increases thyroid radiosensitivity to 131I in both normal and goitrous glands. NA causes a significant increase in thyroid blood flow, which would increase tissue oxygenation and tissue damage via free radicals. Wistar rats were treated with either nicotinamide (NA), 131I or both. The expression of the three isoforms of nitric oxide synthase (NOS) in the thyroid (Western blot) and the activities of SOD, GPx, catalase and organic peroxides were determined. Treatment with NA or 131I increased the expression of eNOS and the generation of organic peroxides. When administered jointly, they showed a synergistic effect. No changes were observed in the other NOS isoforms or in the activities of catalase, glutathione peroxidase and superoxide dismutase. NA potentiates the effect of 131I by increasing eNOS, which would in turn stimulate NO production, increasing thyroid blood flow and tissue damage via organic peroxides.