Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2-receptors

Studies have shown an increased responsiveness of the dopaminergic system after repeated administration of a variety of antidepressant drugs. In the present study, the effect of repeated administration (twice daily for 14 days) of imipramine and mianserin on the affinity of dopamine D2-receptors for quinpirole, a D2-agonist, and on the quinpirole-induced locomotor hyperactivity was examined in rats. Repeated doses of imipramine and mianserin increased the affinity of quinpirole for [3H]spiperone binding sites in membranes prepared from the limbic system but not the striatum. The locomotor hyperactivity induced by quinpirole was enhanced by chronic treatment with both antidepressants. The data indicate that the enhanced responsiveness of the dopaminergic system in rats, observed after chronic treatment with antidepressants, may result from an increased affinity of agonists at D2-receptors in the mesolimbic system.     

Ultrasound appearance of the hip joint in newborns during the first week of life.

The frequency of different types of hip joints in newborns was determined on the basis of ultrasound screening examinations performed during the first week of life. A higher percentage (14.1%) of abnormal hip joints were seen in comparison with the groups examined in later weeks of life suggesting the possibility of natural improvement in a number of cases. The more frequent appearance of pathology in girls was confirmed. Further investigations on the natural history of hip joint development in the newborn and on the general principles of screening examinations are needed.     

Serotonergic modulation of rat pineal gland activity: in vivo evidence for a 5-Hydroxytryptamine(2C) receptor involvement

There are some suggestions that, in the pineal gland, serotonin acts not only as a precursor of melatonin but also plays a role in the modulation of the pineal biosynthetic activity. To corroborate this possible neuromodulatory role of 5-hydroxytryptamine (serotonin) (5-HT) on the pineal gland, the effects of two 5-HT(2) receptor agonists meta-chlorophenylpiperazine (m-CPP) and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane were assessed in vivo on pineal N-acetyltransferase (NAT) activity and melatonin content in rats. m-CPP potentiated the enhancement of NAT activity and pineal melatonin content induced by isoproterenol administration during daytime, whereas it did not affect the diurnal basal biosynthetic activity of the gland. At night, m-CPP and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane enhanced significantly the physiological increases in both pineal NAT activity and melatonin content. This enhancement was prevented by pretreatment with N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea hydrochloride, an antagonist with higher affinity for 5-HT(2B/C) than for 5-HT(2A) receptor, as well as by pretreatment with 8-[5-(2, 4-dimethoxy-5-(4-trifluoromethyl-phenylsulphonamido)-phenyl-5-o xopent hyl]-1,3,8-triazospiro[4,5]decane-2,4-dione, the most specific 5-HT(2C) receptor now available, but not by pretreatment with ketanserin, an antagonist with higher affinity for 5-HT(2A) than for 5-HT(2C) receptor. These results suggest that 5-HT(2C) receptors are likely involved in the mediation of the serotonergic modulation of pineal biosynthetic activity in rats.     

A placebo-controlled efficacy study of the intravesical immunomodulators TMX-101 and TMX-202 in an orthotopic bladder cancer rat model

Purpose

TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model.

Methods

Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically.

Results

No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant (p?=?0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle (p?=?0.005).

Conclusions

TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.

     

Observer agreement for respiratory signs and oximetry in infants hospitalized with lower respiratory infections.

To determine observer agreement for a clinical score and oximetry in lower respiratory infection in children less than 2 yr of age, a convenience sample of 56 infants hospitalized with bronchiolitis or pneumonia was assessed independently by two observers. A total of 12 infants had chronic lung disease of prematurity or congenital heart disease. Infants in whom oxygen supplementation could not be discontinued for at least 5 min were excluded. A severity score was assigned for each of four categories (respiratory rate, retractions, wheeze, and general appearance). A total for each patient was obtained by summing the score for each category. Oxygen saturation was measured using a Nellcor oximeter. Agreement beyond chance was measured using the kappa statistic. The relationship between observers for total score and oximetry and the mean total score and mean oximetry value for each patient was expressed as a Pearson correlation coefficient. A total of 56 infants and children were studied: 2 had pneumonia, 11 had an exacerbation of pulmonary signs and symptoms with their underlying cardiac or pulmonary disease, and 43 had bronchiolitis. Kappa was 0.48 for general assessment, 0.38 for respiratory rate, 0.31 for wheeze, and 0.25 for retractions. All values were statistically significantly greater than 0 at p less than 0.01. Correlations for total score and for oximetry were 0.68 and 0.88, respectively. The median difference between oximetry readings was 1. The correlation coefficient between total score and oximetry was -0.04. The limited agreement for clinical signs makes comparison of patient illness severity between studies difficult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Social skills and neurocognitive individualized training in schizophrenia: comparison with structured leisure activities

Cognitive impairment and deficits in social skills have been largely documented in patients with schizophrenia and are increasingly recognized as rate-limiting factors for recovery. Evidence has been provided that cognitive training and social skills training (SST) are effective to treat cognitive and social skills impairment in schizophrenia; however, the translation of improved performance on cognitive or social skills tasks into improved functional outcome is controversial. According to recent reviews, interventions providing cognitive training in conjunction with psychosocial rehabilitation have a greater impact on functional outcome than either intervention alone suggesting that the two treatment approaches may work together in a synergistic fashion. The present pilot study was designed to test the hypothesis that an integrated rehabilitation program, including individualized cognitive and SST, is more effective than the structured leisure activities (SLA) carried out in many Italian Mental Health Departments. The primary outcome measure was subjects’ personal and social functioning as assessed by the Interview for the assessment of disability. The study is based on a controlled design including randomization to treatment groups, blind assessments and stable pharmacological treatment. Subjects were recruited among patients attending three psychiatric facilities located in the Italian region Campania. Thirty patients were randomized to the experimental program “social skills and neurocognitive individualized training” (SSANIT), and 30 to SLA. The two programs were matched for the overall duration as well as frequency and duration of the sessions. The two groups of patients did not differ at baseline on psychopathology, neurocognitive and personal/social functioning. After 6 months of treatment, personal and social functioning was significantly better in patients assigned to SSANIT than in those assigned to usual rehabilitation activities practiced in Mental Health Departments. No advantage was observed for either program on psychopathological and cognitive outcome indices. As for other integrated programs, also for SSANIT further studies are needed to verify generalization and persistence of the observed gains, and to clarify most adequate length and doses of the therapeutic intervention as well as the relative contribution of each program component to its impact on subjects’ disability.     

Financial and non-financial conflicts of interests in psychiatry

A conflict of interests occurs when a doctor is unduly influenced by a secondary interest (i.e., a personal incentive) in his acts concerning one of the primary interests to which he is professionally committed (the welfare of patients, the progress of science, or the education of students or residents). One specific variety of conflicts of interests has monopolized the attention of the scientific and lay press: the financial conflicts of interests arising from the relationships between doctors and drug companies. A large literature has described the many, sometimes subtle, ways by which a psychiatrist can be influenced in his prescribing habits or research activities by his relationships with the industry. Some empirical evidence is now available in this area. On the other hand, it has been pointed out that the current debate on this issue is sometimes "affectively charged" or fails to take into account that the interests of patients, families and mental health professionals and those of the industry may be often convergent. Other types of conflicts of interests are beginning now to be discussed. There is evidence that the allegiance of a researcher to a given school of thought may influence the results of studies comparing different psychotherapeutic techniques, thus colliding with the primary interest represented by the progress of science. Political commitment is also emerging as a source of conflicts of interests. Financial and non-financial conflicts of interests are widespread in psychiatric practice and research. They cannot be eradicated, but must be managed more effectively than is currently the case.