Zoledronic acid decreases mRNA six-transmembrane epithelial antigen of prostate protein expression in prostate cancer cells.

BACKGROUND: Zoledronic acid (Zol) is used successfully to inhibit bone resorption in tumor bone disease of various human cancer. Zol inhibits the mevalonate pathway and other potential targets include the inhibition of tyrosine phosphatase activity, disruption of metalloproteinase, secretion and down-regulation of the catalytic subunit of telomerase (hTERT). The six-transmembrane epithelial antigen of prostate protein (STEAP) is a new marker highly expressed at all phases of prostate cancer. AIM: Here, we analyzed for the first time the effect of Zol on STEAP gene expression in prostate cancer cells. MATERIAL AND METHODS: We evaluated the effects of Zol in STEAP gene expression by RT real time PCR in androgen-sensitive (LNCaP) and androgen-non-sensitive (PC3 and DU145) cell lines. To confirm the pro-apoptotic effect of Zol, we also analyzed the caspase-3 gene expression, that resulted up-regulated in cancer cell apoptosis. RESULTS: Zol strongly decreased cell viability and lowered STEAP gene expression in a dose-dependent manner. In addition, this effect was accompanied by an increase of apoptotic index and an up-regulation of caspase-3 gene expression. CONCLUSION: Zol may affect cancer cells also by targeting the gene expression of STEAP.

STEAP mRNA detection in serum of patients with solid tumours.

STEAP was identified by the strategy of suppression subtractive hybridizations in Los Angeles prostate cancer xenografts. It is expressed in prostate and other cancers, and not in most normal tissue; it can be used as a marker to evaluate biological samples from individuals suspected of having a disease associated with STEAP dysregulation, such as cancers, and may provide prognostic information useful in defining appropriate therapeutic options. The aim of this study was to test the STEAP mRNA detection in the serum of patients with different malignant tumours by using Real-Time reverse transcription PCR. The results were compared with biological samples obtained by age-matched non-malignant donors. Our data demonstrated that STEAP mRNA is detectable in serum of patients with different solid tumours whereas it is not amplifiable in non-malignant donors. This marker revealed with the molecular method of quantitative PCR in serum, may be useful to discriminate normal and cancer patients.

Professionals' perceptions of psychotropic medication in residential facilities for individuals with mental retardation.

Professional staff in four state facilities for individuals with mental retardation were surveyed to determine their perceptions, knowledge and opinions regarding the use of psychotropic medication. A large majority of the 377 respondents indicated that the physicians in their facilities were primarily responsible for medication-related decisions. Under ideal conditions, however, all professional staff and parents were seen as having a greater influence in the decision-making process. Aggression, delusions and hallucinations, self-injury, other psychiatric disorders, and anxiety were rated as disorders most likely to result in medication therapy. Behaviour modification was viewed as a suitable alternative to drug treatment for acting out and aggression. The professionals indicated that behavioural observation was the most influential assessment technique in current usage, followed by global impressions and informal diaries. Over 80% of the respondents perceived their preservice and inservice training on issues related to the use of psychotropic medication to treat behaviour problems as inadequate, with 96% of them desiring continuing education. These findings were compared to data from similar studies of populations with other disabilities, and suggestions for modifications in the current decision-making processes related to the use of psychotropic medication in institutionalized individuals with mental retardation are discussed.

Effects of thioridazine and visual screening on stereotypy and social behavior in individuals with mental retardation.

Thioridazine and visual screening procedures are effective in reducing the stereotypic behaviors of individuals with mental retardation. A double-blind, placebo-controlled study, using alternating treatments within a multiple-baseline across subjects design, was conducted to assess the effects of two doses of thioridazine (1.25 and 2.5 mg/kg/day) and visual screening, alone and combined, on stereotypy and social behavior of three individuals with profound mental retardation. Functional analyses did not show demand, alone, social attention, or differential reinforcement conditions to maintain the subjects' stereotypy. Thioridazine was effective in producing modest reductions in stereotypy and minor increases in social behavior across subjects. The higher dose of thioridazine (2.5 mg/kg/day) was slightly more effective than the lower dose (1.25 mg/kg/day), and thioridazine plus visual screening was more effective than thioridazine alone. The most effective treatment was visual screening when used in the absence of thioridazine. This study demonstrates a method for assessing the impact of psychopharmacological and behavioral interventions in individuals for whom a behavioral treatment cannot be easily derived from a functional analysis of the maintaining conditions of the target behavior.

Factor structure of the Motivation Assessment Scale.

The Motivation Assessment Scale (MAS) was developed to provide clinical information on four hypothesized functions that may control problem behaviour in persons with developmental disabilities. The original four-factor structure of the MAS was based on face validity, with the items being grouped in terms of each of the hypothesized functions. Validation of the scale was provided in terms of correlations between teacher ratings of eight children on the MAS and ranking of the controlling variables from functional analogue tests. In this study, staff in residential facilities rated 60 residents and teachers in schools rated 96 students on the MAS. The target behaviour rated for both samples was self-injury, with the institutional sample engaging in the behaviour more than 15 times an hour and the school sample, less than 15 times an hour. The results of factor analyses, with varimax rotation, provided a conceptually meaningful factor structure with the institutional sample, but not with the school sample. The 16 MAS items resolved into four factors that were conceptually related to four conditions that may maintain problem behaviour (i.e. sensory, escape, attention and tangible). The results suggested that the original MAS has a robust factor structure and may be clinically useful in predicting the controlling functions of problem behaviours, if the target behaviours occur at a rate no less than 15 responses per hour.

Considerations on the epidemiology of the Seveso accident.

A historical analysis of the Seveso accident and a critical evaluation of the investigations carried out up to now on the subject are reported. On the basis of several considerations, a definition of the magnitude and of the true consequences of the contamination by dioxin and other not clearly identified chemicals, which affected a large area of Northern Italy on July 10 1976, is also attempted.

[Neuropsychopharmacological effects of TCDD]. / Effetti neuropsicofarmacologici della TCDD.

It has been found that TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), in rats, endoperitoneally or orally administered at dose of 1-10 mcg/kg, provokes irritability, aggressivity and restlessness (increase of spontaneous crossings in the shuttle box). The TCDD does not modify the conditioned avoidance (C.A.) or the conflictual situation. In "vitro" the TCDD stimulates directly the striatal and hypothalamic adenylate cyclase of rat. The TCDD increases the stimulation produced by dopamine on striatal adenylate cyclase. Haloperidol (dopamine antagonist) inhibits the stimulation produced by TCDD. TCDD does not significantly modify the stimulation by hystamine on hypothalamic adenylate cyclase. Cimetidine (H2) antagonist) causes a remarkable increase of the TCDD stimulating effect.