Pericytes promote selective vessel regression to regulate vascular patterning

Blood vessel networks form in a 2-step process of sprouting angiogenesis followed by selective branch regression and stabilization of remaining vessels. Pericytes are known to function in stabilizing blood vessels, but their role in vascular sprouting and selective vessel regression is poorly understood. The endosialin (CD248) receptor is expressed by pericytes associated with newly forming but not stable quiescent vessels. In the present study, we used the Endosialin(-/-) mouse as a means to uncover novel roles for pericytes during the process of vascular network formation. We demonstrate in a postnatal retina model that Endosialin(-/-) mice have normal vascular sprouting but are defective in selective vessel regression, leading to increased vessel density. Examination of the Endosialin(-/-) mouse tumor vasculature revealed an equivalent phenotype, indicating that pericytes perform a hitherto unidentified function to promote vessel destabilization and regression in vivo in both physiologic and pathologic angiogenesis. Mechanistically, Endosialin(-/-) mice have no defect in pericyte recruitment. Rather, endosialin binding to an endothelial associated, but not a pericyte associated, basement membrane component induces endothelial cell apoptosis and detachment. The results of the present study advance our understanding of pericyte biology and pericyte/endothelial cell cooperation during vascular patterning and have implications for the design of both pro- and antiangiogenic therapies.     

Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review

Sienaert P, Lambrichts L, Dols A, De Fruyt J.
Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review.
Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment‐resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance. Methods: A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms. Results: Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2). Conclusions: The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.     

Postural orthostatic tachycardia syndrome associated with multiple sclerosis

BackgroundThe aim of this study was to determine if there is a difference in the frequency of postural orthostatic tachycardia syndrome (POTS) in patients with multiple sclerosis (MS) compared to patients with symptoms of orthostatic intolerance and with no evidence of MS or other neurological illness.MethodsWe analyzed data gathered from 293 patients who underwent the head-up tilt table test protocol. Group 1 included prospectively analyzed 112 with MS and group 2 included retrospectively analyzed 181 patients who were evaluated because of symptoms of orthostatic intolerance, and with no evidence of MS or other neurological illness. If POTS was identified the head-up tilt table test was repeated and supine as well as standing serum epinephrine and norepinephrine were determined.ResultsPOTS was identified in 39 patients: 21 (19%) in the MS group comparing to 18 (10%) in the non MS group (p = 0.035). There was no difference between groups in the occurrence of POTS associated syncope (p = 0.52). There was no difference between groups in the epinephrine or norepinephrine in supine and standing positions. While both standing epinephrine and norepinephrine levels were significantly higher compared to levels in the supine position in the non MS group, only standing norepinephrine levels were significantly higher in the MS group.ConclusionsThe results of this study suggest that POTS is associated with MS.