Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.     

Matrix metalloproteinase-2 expression induced by two different adhesive systems on human pulp fibroblasts

Introduction

This study evaluated the expression of matrix metalloproteinase-2 (MMP-2) in primary cultures of human pulp fibroblasts (HPFs) when exposed to extracts from dentin-bonding systems.

Methods

Polymerized resin disks of the bonding agent of a 2-step self-etch adhesive (TechBond, Isasan, Rovello Porro, Italy) or of the primer/bonding agent a 2-step etch-and-rinse adhesive (Optibond Solo; Sybron-Kerr, Orange, CA) were immersed in HPF culture medium for 24 or 96 hours. HPFs were incubated in the adhesive-conditioned or control (untreated) culture medium for 24 hours. Western blot and immunofluorescence analyses were performed to assay MMP-2 expression.

Results

MMP-2 expression levels in HPFs cultured for 24 hours in culture medium were similar in both the control and experimental media groups showing a faint band at 67 kDa. Conversely, the HPFs incubated in the medium that contain polymerized resin disks for 96 hours showed increased MMP-2 expression compared with the untreated medium. The self-etch adhesive displayed the most pronounced induction of MMP-2 expression. These findings were confirmed by immunofluorescence analysis.

Conclusions

HPFs display increased MMP-2 expression after 96 hours of conditioning of the HPF culture medium with polymerized disks of dentin bonding systems. This MMP-2 expression/activation may represent a defence mechanism exhibited by HPFs towards monomers eluted from the dentin bonding systems.     

RSK2 enzymatic assay as a second level diagnostic tool in Coffin-Lowry syndrome

BACKGROUND: Coffin-Lowry syndrome is a semi-dominant condition characterized by severe psychomotor retardation with facial, hand and skeletal malformations resulting from mutations in RSK2 gene, encoding for a serine/threonine kinase. More than 100 different mutations have been identified to date; however, about 50% of clinically diagnosed patients apparently do not have mutations. In order to exclude that these patients have RSK2 mutations missed by standard mutation detection techniques, a rapid and sensitive assay allowing evaluation of RSK2 activity was needed. METHODS: RSK2 capacity to phosphorylate a synthetic CREB-peptide in basal and PMA-stimulated conditions was evaluated in lymphoblasts from 3 patients with RSK2 mutations and normal controls. RESULTS: Patients RSK2 activity is normal in nonstimulated conditions but fails to grow following stimulation. The evaluation of the stimulated/non-stimulated activity ratio demonstrated a statistically significant impairment in patients. CONCLUSIONS: We have set up an assay which allows the identification of even partial alterations of RSK2 activity and seems to give good results also in females with a balanced X-chromosome inactivation and thus with a presumably normal enzymatic activity in about 50% of cells. Moreover, our data seem to confirm previous reports of a potential direct correlation between the level of RSK2 activity and the severity of cognitive impairment.     

Evaluation and management of joint pain

The purpose of this article was to provide a review for orthopaedic nurses and nurse practitioners who evaluate, manage, and care for patients with joint pain. Joint pain is a common complaint evaluated by primary care providers. The causation of joint pain is complicated to identify because of an extensive range of differential diagnosis. The history and physical examination are crucial components in evaluating and managing joint pain. The primary care provider uses clinical factors such as patient demographics, presence of inflammation, acute/chronic duration, extra-articular manifestations, pattern of joint involvement, and disease chronology. Many rheumatologic laboratory tests are nonspecific, but aspiration of the joint with synovial fluid analysis may provide diagnostic clues, especially to differentiate infection versus inflammation. Primary care providers utilize both pharmacologic and nonpharmacologic regimens to manage acute and chronic joint pain.     

Transient elastography identifies liver recipients with nonviral graft disease after transplantation: a guide for liver biopsy

Transient elastography (TE) reliably predicts the severity of recurrent hepatitis C virus after orthotopic liver transplantation (OLT); however, its accuracy in evaluating nonviral liver graft damage is unknown. Between 2006 and 2009, 69 OLT recipients [37 for hepatitis B virus/hepatitis D virus (recurrence-free), 20 for autoimmune/cholestatic liver disease, 6 for alcoholic liver disease, and 6 for mixed etiologies] underwent protocol/on-demand liver biopsy (LB) and concomitant TE. A histological diagnosis of graft disease was made according to criteria defined by the Banff working group. Sixty-five patients (94%) had reliable TE examinations during a median post-OLT follow-up of 18 months (range = 7-251 months). LB samples (median length = 35 mm) showed graft damage in 28 patients (43%): idiopathic chronic hepatitis (11), steatohepatitis (3), rejection (3), cholangitis (2), and autoimmune/cholestatic recurrence (9). Patients with graft damage had significantly higher serum liver enzyme levels and TE results (median = 7.8 kPa, range = 5.4-27.4 kPa) than the 37 patients without graft damage (median = 5.3 kPa, range = 3.1-7.4 kPa, P < 0.001). By a receiver operating characteristic curve analysis, 2 TE cutoffs for the diagnosis of graft damage were identified: 5.3 kPa with 100% sensitivity and 7.4 kPa with 100% specificity. The pretest probability of graft damage was 43%; in patients with TE values ≤5.3 kPa, the posttest probability of graft damage fell to 0%, but in patients with TE results >7.4 kPa, the posttest probability increased to 100%. In conclusion, the dual TE cutoff allows accurate discrimination between the absence and presence of nonviral liver graft damage and improves the clinical management of OLT recipients in terms of the selection of patients most in need of LB.