Diazepam impairs place learning in naive but not in maze-experienced rats in the Morris water maze

Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.     

Functional analysis of cytotoxic cells in patients with acute nonlymphoblastic leukemia in complete remission

In the current study, we investigated the cytotoxic ability of peripheral blood mononuclear cells (PBMC) recovered from patients with acute nonlymphoblastic leukemia (ANLL) in complete remission (CR) against natural killer (NK)-sensitive, NK-resistant, autologous and allogeneic leukemic target cells taken at diagnosis. Our purpose was to define the role played by cytotoxic mechanisms in the control of leukemic cell growth in ANLL. Experiments were carried out at resting conditions and after in vitro activation with recombinant interleukin-2 (rIL-2) and anti-CD3 monoclonal antibody (moAb). At resting conditions, PBMC recovered from ANLL patients displayed a NK function that was not significantly different from controls (mean +/- standard error of the mean [SEM]: 21.9% +/- 3.9% versus control values of 27.5% +/- 2.9%; the P value was not significant [NS]), but they were unable to show cytotoxic activity against autologous and allogeneic leukemic cells. After in vitro boosting with rIL-2, PBMC were able to generate lymphokine activated killer (LAK) cells, as demonstrated by an increased killing of NK-resistant Daudi targets (16.3% +/- 2.7%). Although LAK activity was quantitatively lower than in control subjects (mean +/- SEM: 16.3% +/- 2.7% versus control values of 79.8% +/- 3.1%; P less than 0.001), it still exerted a cytotoxic effect against autologous and allogeneic leukemic cells. Similar results were obtained when anti-CD3 moAb was used as a stimulus in vitro. Our data suggest that nonspecific cytotoxic cells may be triggered to exert an in vitro cytotoxic effect on leukemic cells, which could possibly play a key role in vivo in the control of leukemic cell growth regulation.     

Age-dependent changes in the mitochondrial F0F1 ATP synthase

The age dependence of ATP hydrolase activity and oligomycin sensitive passive proton conduction in sonicated submitochondrial particles of rat brain and rat heart has been investigated. The results show an increase of Vmax of the ATP hydrolase activity and decrease of oligomycin sensitive passive proton conduction with increase of the age of rats from 3 to 6 months. Decrease of ATPase activity and increase of oligomycin sensitive proton conduction occur with further aging to 24 months. Immunoblot analysis shows that both the F(1) and F(0) contents of mitochondria vary with the age of rats, the former exhibiting relatively larger changes.     

Mediterranean Alcohol-Drinking Pattern and the Incidence of Cardiovascular Disease and Cardiovascular Mortality: The SUN Project

Background: We assessed the still unclear effect of the overall alcohol-drinking pattern, beyond the amount of alcohol consumed, on the incidence of cardiovascular clinical disease (CVD). Methods: We followed 14,651 participants during up to 14 years. We built a score assessing simultaneously seven dimensions of alcohol consumption to capture the conformity to a traditional Mediterranean alcohol-drinking pattern (MADP). It positively scored moderate alcohol intake, alcohol intake spread out over the week, low spirit consumption, preference for wine, red wine consumption, wine consumed during meals and avoidance of binge drinking. Results: During 142,177 person-years of follow-up, 127 incident cases of CVD (myocardial infarction, stroke or cardiovascular mortality) were identified. Compared with the category of better conformity with the MADP, the low-adherence group exhibited a non-significantly higher risk (HR) of total CVD ((95% CI) = 1.55 (0.58–4.16)). This direct association with a departure from the traditional MADP was even stronger for cardiovascular mortality (HR (95% CI) = 3.35 (0.77–14.5)). Nevertheless, all these associations were statistically non-significant. Conclusion: Better conformity with the MADP seemed to be associated with lower cardiovascular risk in most point estimates; however, no significant results were found and more powered studies are needed to clarify the role of the MADP on CVD.     

Incidence,mortality, and national costs of hospital admissions for potentially preventable infections in patients with rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) patients have high infection rates. Streptococcus pneumoniae, herpes zoster (HZV), and influenza are common and potentially preventable causes of...     

Dihydroergocriptine in management of microprolactinomas

The effects of dihydroergocriptine (DHECP), a dihydrogenated ergot alkaloid with dopaminergic agonistic and alpha-adrenergic antagonistic properties, were studied in 22 women with PRL-secreting microprolactinomas and compared with those recorded in 36 previously studied patients treated with bromocriptine (BRC). After acute administration of 5 mg DHECP, orally, serum PRL decreased by 61 +/- 18% (+/- SD); only 1 patient was unresponsive. The nadir was reached at 300 min. Long term treatment with increasing DHECP doses caused a progressive PRL fall from 125 +/- 142 (+/- SD) to 81 +/- 159 micrograms/L after 1 week of a 3 mg twice daily regimen, to 64 +/- 88 micrograms/L after 1 week of 5 mg twice daily, 46 +/- 57 micrograms/L after 1 week of 10 mg twice daily, and 28 +/- 34 to 33 +/- 45 micrograms/L throughout 9 months of treatment with 10 mg DHECP 3 times daily. Seventy-seven percent of patients had normal serum PRL levels during chronic treatment. All women, including those with supranormal serum PRL levels, resumed regular menses, and 16 had ovulatory cycles; 1 woman became pregnant. Galactorrhea disappeared in all. During treatment the PRL response to TRH, initially absent in all patients, became positive in 10. In 7 patients, after DHECP treatment for 9 months, high definition computed tomographic scan no longer showed the focal lesions initially seen. After drug withdrawal, serum PRL increased again in all except 1 patient. Two patients had regular menses for 6 months, and 3 still had no adenoma imaged by high definition computed tomography. In BRC-treated patients the serum PRL changes and clinical results were very similar to those in the DHECP-treated patients, except for the persistence of normal serum PRL levels in 4 patients after drug withdrawal. On the other hand, side-effects were negligible during DHECP treatment, but remarkable during BRC. Systolic and diastolic blood pressures decreased by only 5.4 and 3.0 mm Hg, respectively, after acute 5 mg DHECP administration, but decreased by 12.8 and 14 mm Hg after acute 2.5 mg BRC administration. Orthostatic hypotension and peripheral vasomotor phenomena occurred in the long term DHECP treated patients except one, but they occurred in 9 and 3 of those treated with BRC, respectively. Gastric discomfort or mild nausea occurred in 12 DHECP-treated patients, while mild or severe nausea or vomiting were observed in 18, 11, and 2 of those taking BRC, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Enhancing Social Initiations Using Naturalistic Behavioral Intervention: Outcomes from a Randomized Controlled Trial for Children with Autism

Deficits in social skills are common in children with Autism Spectrum Disorder (ASD), and there is an urgent need for effective social skills interventions, especially for improving interactions with typically developing peers. This study examined the effects of a naturalistic behavioral social skills intervention in improving social initiations to peers through a randomized controlled trial. Analyses of multimethod, multi-informant measures indicated that children in the active group (SIMI) demonstrated greater improvement in the types of initiations which were systematically prompted and reinforced during treatment (i.e., behavior regulation). Generalization to joint attention and social interaction initiation types, as well as collateral gains in broader social functioning on clinician- and parent-rated standardized measures were also observed.