Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management.

Bisphosphonates (BPs) are widely used in the treatment of postmenopausal osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively).

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.

A critical update on psychological interventions for bipolar disorders.

Although pharmacotherapy is the mainstay of treatment for bipolar disorder, the combination of evidence-based psychological interventions and drug treatment enhances overall effectiveness, mostly by further protecting patients from relapse/recurrence. In recent years, well-designed controlled studies have added weight to evidence favoring specific psychotherapy modalities for bipolar disorders. However, critical issues that may limit the benefits of psychotherapy in day-to-day clinical practice have emerged.

Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis.

Objective: While the role of osteoclasts in bone loss has been well investigated, the involvement of osteoblast-lineage cells has not been completely elucidated. Several genes contribute to normal osteoblastic differentiation from mesenchymal stem cells (MSCs), but an understanding of their role in the pathogenesis of osteoporosis is still lacking. The present study was undertaken to evaluate a possible alteration of osteogenic gene expression as a mechanism contributing to bone loss.

Fire effects on the population structure of Zanthoxylum rhoifolium Lam (Rutaceae) in a Brazilian savanna.

Since cerrado fires may impede the growth of seedlings into trees, they may shape the population of woody species. In this study, we assessed the effects of a severe fire on the population structure and spatial distribution of Zanthoxylum rhoifolium, a widespread cerrado tree. We were interested to know the importance of the resprouting and sexual reproduction in regenerating the population.

Acute limbic encephalitis and glutamic acid decarboxylase antibodies: a reality?

Limbic encephalitis (LE) associated with glutamic acid decarboxylase antibodies (GAD-Ab) is rare. We describe a 30-year-old male with acute LE and GAD-Ab, with follow-up during 2 years of cognitive status including verbal episodic memory, number of seizures recorded by high-resolution video-EEG, brain MRI, 2-[18F]-fluoro-2-deoxyglucose PET and GAD-Ab titres. Treatment with corticosteroids, IV immunoglobulins, immunosuppressors and antiepileptic drugs resulted in improved memory status, disappearance of seizures and decreased GAD-Ab titres.

[Is there a bridge between migraine and familial mesial temporal lobe epilepsy?].

Numerous reviews have emphasized the links between certain types of epilepsy and migraine. Historically, Gowers was one of the first, in 1907, to have drawn attention to a possible relationship between migraine headache and epilepsy in a period when no additional examination was available. In the last two decades, progress in molecular biology, electrophysiology, and neuro-imaging has enabled a better approach to the fundamental elements underlying the interrelationship between these two nosological domains.

From rolandic epilepsy to continuous spike-and-waves during sleep and Landau-Kleffner syndromes: insights into possible genetic factors.

Epilepsy is a frequent neurologic disease in childhood, characterized by recurrent seizures and sometimes with major effects on social, behavioral, and cognitive development. Childhood focal epilepsies particularly are age-related diseases mainly occurring during developmental critical periods. A complex interplay between brain development and maturation processes and susceptibility genes may contribute to the development of various childhood epileptic syndromes associated with language and cognitive deficits.

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria).

Retrospective survival analysis of 261 lithium disilicate crowns in a private general practice.

Objectives: This retrospective study evaluated the clinical performance and long-term survival of glass-ceramic lithium disilicate all-ceramic restorations in anterior and posterior areas over a 10-year period.

Method And Materials: Following a consistent protocol over 10 years, 261 lithium disilicate crowns (IPS Empress 2, Ivoclar Vivadent), including 101 anterior (38.7%) and 160 posterior (61.

Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone.

Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential molecular therapeutic agents for the treatment of cancer. Here we describe novel 2-aminothieno[2,3-d]pyrimidine ATP competitive Hsp90 inhibitors, which were designed by combining structural elements of distinct low affinity hits generated from fragment-based and in silico screening exercises in concert with structural information from X-ray protein crystallography. Examples from this series have high affinity (IC50 = 50-100 nM) for Hsp90 as measured in a fluorescence polarization (FP) competitive binding assay and are active in human cancer cell lines where they inhibit cell proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72.

Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941.

The phosphatidylinositide 3-kinase pathway is frequently deregulated in human cancers and inhibitors offer considerable therapeutic potential. We previously described the promising tricyclic pyridofuropyrimidine lead and chemical tool compound PI-103. We now report the properties of the pharmaceutically optimized bicyclic thienopyrimidine derivatives PI-540 and PI-620 and the resulting clinical development candidate GDC-0941.

SPM analysis of ictal-interictal SPECT in mesial temporal lobe epilepsy: relationships between ictal semiology and perfusion changes.

A combination of temporo-limbic hyperperfusion and extratemporal hypoperfusion was observed during complex partial seizures (CPS) in temporal lobe epilepsy (TLE). To investigate the clinical correlate of perfusion changes in TLE, we analyzed focal seizures of increasing severity using voxel-based analysis of ictal SPECT. We selected 26 pre-operative pairs of ictal-interictal SPECTs from adult mesial TLE patients, seizure-free after surgery.

Eyelid fluttering, typical EEG pattern, and impaired intellectual function: a homogeneous epileptic condition among the patients presenting with eyelid myoclonia.

Purpose: This retrospective study aims to review the electroclinical features of patients presenting with eyelid myoclonia (EM) with and without absences.

Methods: The Italian chapter of the International League Against Epilepsy (ILAE) has been conducting an electroclinical study of patients with EM. Among these, we searched for and selected the patients presenting with both impairment of intellectual functions and a peculiar ictal electroencephalography (EEG) pattern, that is, a discharge of fast generalized polyspikes/polyspikes and waves.

Ultrastructural study of archaeological Vitis vinifera L. seeds using rapid-freeze fixation and substitution.

The ultrastructure of Vitis vinifera seeds from different archaeological sites was studied. Preservation status differed between sites. Preliminary investigations of grape seeds from Poggio Bacherina (Chianciano Terme, Siena) and Miranduolo (Chiusdino, Siena) showed collapsed or charred tegument, making this material suitable for morphometric studies only.

Road traffic injuries in one local health unit in the Lazio region: results of a surveillance system integrating police and health data.

Objective: Different sources are available for the surveillance of Road Traffic injuries (RTI), but studied individually they present several limits. In this paper we present the results of a surveillance integrating healthcare data with the data gathered by the municipal police in the southeastern area of Rome (630,000 inhabitants) during the year 2003.

Methods: The Municipal police RTI reports, which list the exact location, circumstances and some risk factor of the crash, were searched in the emergency visit, hospitalization and mortality databases, to integrate them with the information on health consequences.

A dynamic model of client recruitment and retention in community-based HIV prevention programs.

The study used system dynamics modeling computer simulations to gain a better understanding of the process of delivering small-group, evidence-based HIV prevention programs in the community and to explore implications for public health practice. A model was developed to explain provider-reported challenges associated with recruiting, retaining, and graduating people from small-group workshop programs. The model simulations revealed the difficulty in sustaining high rates of recruitment and retention in small-group programs over time.

Long-term mental health resource utilization and cost of care following group psychoeducation or unstructured group support for bipolar disorders: a cost-benefit analysis.

Objective: To explore the short- and long-term mental health resource utilization and cost of care in a sample of 120 individuals with bipolar disorders who participated in a randomized controlled efficacy trial of group psychoeducation versus unstructured group support.

Method: Prospective, independent monitoring of DSM-IV bipolar disorder type I or II patients aged 18 to 65 years was conducted during the intervention phase (6 months) and follow-up phase (5-year postintervention) of a randomized controlled trial reporting clinical outcomes and inpatient and outpatient mental health service utilization, with estimation of cost of treatment per patient. The study was conducted from October 1997 through October 2006.

Small-molecule activation of p53 blocks hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in vivo and leads to tumor cell apoptosis in normoxia and hypoxia.

The p53 tumor suppressor protein negatively regulates hypoxia-inducible factor 1alpha (HIF-1alpha). Here, we show that induction of p53 by the small-molecule RITA (reactivation of p53 and induction of tumor cell apoptosis) [2,5-bis(5-hydroxymethyl-2-thienyl) furan] (NSC-652287) inhibits HIF-1alpha and vascular endothelial growth factor expression in vivo and induces significant tumor cell apoptosis in normoxia and hypoxia in p53-positive cells. RITA has been proposed to stabilize p53 by inhibiting the p53-HDM2 interaction.

Non-Epileptic Seizures (NES) are predicted by depressive and dissociative symptoms.

Objectives: (1) To measure depressive and dissociative symptoms in a population of patients with Non-Epileptic Seizures (NES, or pseudo-seizures); (2) To compare NES with Epileptic subjects and Normal controls; (3) To try to define a personality profile specific, or typical, of NES patients.

Patients: 30 consecutive patients (21 females and 9 males, mean age 32.9+/-11.

Molecular pharmacology of phosphatidylinositol 3-kinase inhibition in human glioma.

Gliomas are primary brain tumors with poor prognosis that exhibit frequent abnormalities in phosphatidylinositol 3-kinase (PI3 kinase) signaling. We investigated the molecular mechanism of action of the isoform-selective class I PI3 kinase and mTOR inhibitor PI-103 in human glioma cells. The potent inhibitory effects of PI-103 on the PI3 kinase pathway were quantified.