STAT pathway in the regulation of zoledronic acid-induced apoptosis in chronic myeloid leukemia cells

In this study, we aimed to evaluate the cytotoxic and apoptotic effects of zoledronic acid on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on zoledronic acid-induced apoptosis. The results showed that zoledronic acid decreased proliferation, and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT3, -5A and -5B genes were significantly reduced in zoledronic acid-treated K562 cells. These data indicated that STAT inhibition by zoledronic acid may be therapeutic in CML patients following the confirmation with clinical studies.     

Ghrelin injected into the paraventricular nucleus of the hypothalamus of male rats induces feeding but not penile erection

The effect of ghrelin, a recently characterized endogenous receptor agonist for growth hormone (GH) secretagogue receptors, on feeding and penile erection was compared with that of EP 80661, a peptide analogue of the GH secretagogue hexarelin, previously identified for its pro-erectile activity when injected into the paraventricular nucleus of the hypothalamus of male rats. Ghrelin (0.01-1 microg), but not EP 80661 (0.02-1 microg), was found to be particularly effective in enhancing feeding. The minimal effective dose of ghrelin was 0.1 microg, which increased food intake by 88%, while the maximal response (355% above control values) was found with 1 microg of the peptide. The enhancing effect of ghrelin on feeding was prevented by the prior administration of the neuropeptide Y Y5 receptor antagonist (DTyr(2), DThr(32)) neuropeptide Y (NPY, 10 microg), but not by the GH-RH receptor antagonist MZ-4-71 (10 microg), or by EP 91073, a hexarelin analogue that antagonizes the pro-erectile effect of EP 80661 (10 microg), given into the lateral ventricles. In contrast, ghrelin failed to induce penile erection at all doses tested, while EP 80661 induced penile erection in a dose-dependent manner. The pro-erectile effect of EP 80661 was prevented by EP 91073 (10 microg), but not by (DTyr(2), DThr(32)) NPY (10 microg) or by the GH-RH receptor antagonist MZ 4-71 (10 microg), given into the lateral ventricles. The present results provide further support to the hypothesis that the GH secretagogue receptors mediating feeding are different from those mediating penile erection and activated by pro-erectile EP peptides.     

Dissociation of haloperidol, clozapine, and olanzapine effects on electrical activity of mesocortical dopamine neurons and dopamine release in the prefrontal cortex.

The aim of the present study was to compare the effects of the typical antipsychotic haloperidol and the atypical antipsychotics clozapine and olanzapine on both extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) as well as electrical activity of mesoprefrontal DA (mPFC-DA) neurons. Extracellular single unit recordings and microdialysis experiments were carried out in different groups of chloral hydrate anesthetised rats under identical experimental conditions. Intravenous administration of haloperidol, clozapine, and olanzapine increased the firing rate and burst activity of antidromically-identified mPFC-DA neurons; maximal increase in firing rate of approximately 140, 155, and 70 %, was produced by haloperidol, clozapine, and olanzapine at doses of 0.2, 2.5, and 1 mg/kg, i.v., respectively. Intravenous administration of the same doses increased extracellular DA levels in mPFC by 20%, 190%, and 70%, respectively. Moreover, while haloperidol and olanzapine increased extracellular levels of the deaminated DA metabolite DOPAC, by 60% and 40%, respectively, clozapine was totally ineffective. The D1 receptor antagonist SCH 23390 modified neither DA output nor neuronal firing. To determine whether the effect of the three antipsychotics on DA release might depend on a direct action on the mPFC, rats were perfused locally via inverse dialysis in the mPFC at concentrations ranging from 10(-6) to 10(-4)M. While clozapine and olanzapine increased extracellular DA concentrations by up to 400% of basal level, haloperidol was totally ineffective. The results obtained from this study indicate that the rank potency of the three antipsychotics in stimulating the firing rate of DA neurons projecting to mPFC, correlates with their affinity for D2 receptors and doses used clinically. On the other hand, their stimulating effect on DA release does not correlate with their effect on neuronal firing but depends on a direct action on the mPFC.     

Parkinsonism and dementia are negative prognostic factors for the outcome of subdural hematoma

To determine, among a population with subdural hematoma (SH), whether patients affected by neurodegenerative disorders (parkinsonism and dementia) have a worse clinical outcome. We reviewed the data of patients diagnosed with fall-related SH discharged from the Departments of Neurology/Stroke unit, Neurosurgery, Intensive Care Unit at Brotzu General Hospital (Cagliari, Italy) between January 2010 and December 2013. Patients with severe traumatisms, evidence of spontaneous intracerebral bleeding or aged less than 50 were excluded. 332 patients were selected: 69 with a neurodegenerative parkinsonism or dementia (N-group), 217 with history of chronic non-neurological medical conditions with significant disability, previous falls and/or balance problems (NND-group) and 46 with a history of “minor” chronic non-neurological disorder. (NN-group). The clinical status at admission and discharge was assessed by modified Rankin Scale (mRS). The time-span between trauma and hospital admission was also calculated. At hospital admission we found a significantly longer delay in SH’s diagnosis (χ ² test p < 0.001) and a worse mRS score (Kruskal Wallis p < 0.001) in the N-group compared to both NN and NND-groups. During hospital stay we observed the lack of significant variation in mRS score in N-group (Wilcoxon test p = 0.86), in contrast with NN and NND-groups who significantly improved (Wilcoxon test p < 0.001). Our results demonstrate that the consequences of SH are more severe in the N-group compared to NN and NND-groups. The longer interval between trauma and hospital admittance plays a critical role in worsening the outcome of patients with parkinsonism and dementia compared to subjects without neurodegenerative disorders.     

Post-natalizumab clinical and radiological findings in a cohort of multiple sclerosis patients: 12-month follow-up

There is an urgent need to identify the best strategies to prevent the loss of natalizumab (N) beneficial effects after its suspension. The objective is to evaluate the clinical and radiological disease activity and to test the efficacy of immunomodulatory/immunosuppressive drugs (IT) after N suspension. Clinical and radiological data from 54 patients 2 years before treatment (pre-N), during treatment (on-N) and after interruption, during 1-year follow-up (post-N) were retrospectively collected. Annualized relapse rate (ARR), expanded disability status scale (EDSS), presence of new T2 lesions and Gd+ (gadolinium enhancing) T1 lesions were evaluated. Pre-N ARR at 1 year was 1.74 while post-N ARR was 0.94 (p = 0.0053). We observed that post-N disease activity never raised over pre-N levels, neither post-N ARR nor post-N EDSS. In patients retreated with N after suspension, post-N ARR was significantly lower than pre-N ARR (p = 0.017), but not in patients treated with other IT or in patients not treated with any disease modifying drugs (DMD). The mean time of freedom from new T2 lesions and new Gd+ lesions was lower in post-N period compared to on-N (T2 lesions p = 0.0000, Gd+ lesions p = 0.0000). In conclusion, a “rebound” pattern was not identified in our cohort, though the disease activity rapidly returned after N, regardless of the treatment used.     

Therapeutic approach to intrusive luxation injuries in primary dentition. A clinical follow-up study.

AIM: This paper reports the results of a fifteen-year study carried out at the Dentoalveolar trauma study Centre of the University of Cagliari Dental Department, on treatment modes utilised for the recovery of periodontal injuries in primary dentition. MATERIALS AND METHODS: The data referred to dental injuries were collected and recorded according to Andreasen's dental trauma classification: clinical signs and symptoms, patient's age and gender, lesion site and extent of the injury, timeframe between trauma and first dental examination. The authors focused their attention on intrusive luxations in primary dentition, which are a very frequent trauma in children between 1 and 4 years of age. It is extremely difficult to treat such injuries and there is an ongoing discussion about the advisability of extracting the intruded teeth, as opposed to wait and assist their natural repositioning using non-invasive techniques aimed at the maintenance of the eruptive space in the dental arch. RESULTS: This careful conservative approach allowed the repositioning of about 60% of the 85 intruded teeth examined. It substantially reduced the number and severity of undesirable sequelae, both local (enamel-hypoplasia) and occlusal (tooth retention), so that only in about 25% of the followed-up cases damages of the successor tooth were found in the permanent dentition. CONCLUSION: The authors conclude their study emphasizing that all those involved in paediatric dentistry must be familiar with periodontal injuries and trained in their treatment, particularly as regards intrusive luxations in primary dentition.     

Development and Characterization of a Standard Closed Tibial Fracture Model in the Rat

Purpose:  

The aim of this study was to develop a clinically relevant standardized closed tibial fracture model in the rat and to characterize the healing process at different time points using radiologic, biomechanical, and histological methods.     

Sterility

Whether or not you are still swimming in the gene pool, if you are a member of a flight crew, this article is intended to help you avoid that ultimate form of sterility known as death. Sterile cockpit is an aviation term meaning the absence of nonessential conversation, not silence. This concept is really important to flight crews for a number of very exciting reasons.     

Suturing of a textured breast implant filled with cohesive silicone gel to prevent dislocation.

We present a case of unilateral anchoring of a style 410 breast implant filled with cohesive silicone gel (McGhan) with four 3/0 braided polyester (Mersilene) sutures. Reoperation after one week and magnetic resonance scanning after six months showed no leakage or bleeding of the prosthesis. Fixation is possible because of the development of cohesive silicone gel in breast implants. Follow up of this patient is necessary for evaluation of long term results.