Transient receptor potential (TRP) cation channels are emerging in vascular biology. In particular, the expression of the capsaicin receptor (TRPV1) was reported in vascular smooth muscle cells. This ...study characterized the arteriolar TRPV1 function and expression in the rat. TRPV1 mRNA was expressed in various vascular beds. Six commercially available antibodies were tested for TRPV1 specificity. Two of them were specific (immunostaining was abolished by blocking peptides) for neuronal TRPV1 and one recognized vascular TRPV1. TRPV1 was expressed in blood vessels in the skeletal muscle, mesenteric and skin tissues, as well as in the aorta and carotid arteries. TRPV1 expression was found to be regulated at the level of individual blood vessels, where some vessels expressed, while others did not express TRPV1 in the same tissue sections. Capsaicin (a TRPV1 agonist) evoked constrictions in skeletal muscle arteries and in the carotid artery, but had no effect on the femoral and mesenteric arteries or the aorta. In blood vessels, TRPV1 expression was detected in most of the large arteries, but there were striking differences at level of the small arteries. TRPV1 activity was suppressed in some isolated arteries. This tightly regulated expression and function suggests a physiological role for vascular TRPV1.
Paravascular drainage of solutes, including β-amyloid (Aβ), appears to be an important process in brain health and diseases such as Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). ...However, the major driving force for clearance remains largely unknown. Here we used in vivo two-photon microscopy in awake head-fixed mice to assess the role of spontaneous vasomotion in paravascular clearance. Vasomotion correlated with paravascular clearance of fluorescent dextran from the interstitial fluid. Increasing the amplitude of vasomotion by means of visually evoked vascular responses resulted in increased clearance rates in the visual cortex of awake mice. Evoked vascular reactivity was impaired in mice with CAA, which corresponded to slower clearance rates. Our findings suggest that low-frequency arteriolar oscillations drive drainage of solutes. Targeting naturally occurring vasomotion in patients with CAA or AD may be a promising early therapeutic option for prevention of Aβ accumulation in the brain.
•Spontaneous low-frequency oscillations can be observed in arterioles in awake mice•Vasomotion drives paravascular clearance of solutes from the brain•Paravascular clearance is impaired in the context of cerebral amyloid angiopathy
van Veluw et al. demonstrate that vasomotion is a major driving force for paravascular clearance of solutes from the brain. Loss of vascular smooth muscle cells and reduced vasomotion in the context of amyloid deposition is associated with impaired clearance.
Tumor endothelial markers (TEMs) that are highly expressed in human tumor vasculature compared with vasculature in normal tissue hold clear therapeutic potential. We report that the C-type lectin ...CLEC14A is a novel TEM. Immunohistochemical and immunofluorescence staining of tissue arrays has shown that CLEC14A is strongly expressed in tumor vasculature when compared with vessels in normal tissue. CLEC14A overexpression in tumor vessels was seen in a wide range of solid tumor types. Functional studies showed that CLEC14A induces filopodia and facilitates endothelial migration, tube formation and vascular development in zebrafish that is, CLEC14A regulates pro-angiogenic phenotypes. CLEC14A antisera inhibited cell migration and tube formation, suggesting that anti-CLEC14A antibodies may have anti-angiogenic activity. Finally, in endothelial cultures, expression of CLEC14A increased at low shear stress, and we hypothesize that low shear stress due to poor blood flow in the disorganized tumor vasculature induces expression of CLEC14A on tumor vessels and pro-angiogenic phenotypes.
Purpose
Surgical exploration and bowel resection are frequently required for treating non-occlusive mesenteric ischemia. Intraoperative evaluation of intestinal perfusion is subjective and ...challenging. In this feasibility study, ICG fluorescence angiography was performed in order to evaluate intestinal perfusion in patients with acute mesenteric ischemia.
Methods
This is a retrospective analysis of 52 patients who were operated for acute mesenteric ischemia using ICG fluorescence angiography. Patients with occlusive disease requiring recanalization were excluded. The SPY and PinPoint imaging systems were used for open and laparoscopic surgery, respectively. Intraoperative macroscopic assessment of perfusion was compared with the ICG angiography results.
Results
Surgical exploration was performed for ischemia of the colon (
n
= 12), the small bowel (
n
= 23), or both (
n
= 16). One patient had ischemia of the esophagus and stomach. All patients had a preoperative CT angiography to rule out stenosis or occlusion of the mesenteric vessels. In 18 cases (34.6%), ICG fluorescence angiography provided information that was supplemental to macroscopic evaluation, but most patients did not survive the postoperative course. However, in six of those cases (11.5%), ICG angiography led to a major change in operative strategy resulting in a significant clinical benefit for those patients. For two cases, ICG fluorescence produced false negative results.
Discussion
ICG tissue angiography is feasible and technically reliable for evaluating intestinal perfusion in acute mesenteric ischemia and led to a significant clinical benefit in 11% of our patients. A relevant discrepancy between surgical visual assessment and fluorescence angiography was found in 35% of the cases, which may help to define resection margins more accurately and thus support surgical decision-making.
Objectives
To explore which preoperative clinical data and conventional MRI findings may indicate microvascular invasion (MVI) of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and have ...clinical significance.
Methods
The study enrolled 113 patients with histopathologically confirmed cHCC-CCA (MVI-positive group
n
= 56, MVI-negative group
n
= 57). Two radiologists retrospectively assessed the preoperative MRI features (qualitative analysis of morphology and dynamic enhancement features), and each lesion was assigned according to the LI-RADS. Preoperative clinical data were also evaluated. Logistic regression analyses were used to assess the relative value of these parameters as potential predictors of MVI. Recurrence-free survival (RFS) rates after hepatectomy in the two groups were estimated using Kaplan–Meier survival curves and compared using the log-rank test.
Results
The majority of cHCC-CCAs were categorized as LR-M. On multivariate analysis, a higher serum AFP level (OR, 0.523; 95% CI, 0.282–0.971;
p
= 0.040), intratumoral fat deposition (OR, 14.368; 95% CI, 2.749–75.098;
p
= 0.002), and irregular arterial peritumoral enhancement (OR, 0.322; 95% CI, 0.164–0.631;
p
= 0.001) were independent variables associated with the MVI of cHCC-CCA. After hepatectomy, patients with MVI of cHCC-CCA showed earlier recurrence than those without MVI (hazard ratio HR, 0.402; 95% CI, 0.189–0.854,
p
= 0.013).
Conclusion
A higher serum AFP level and irregular arterial peritumoral enhancement are potential predictive biomarkers for the MVI of cHCC-CCA, while intratumoral fat detected on MRI suggests a low risk of MVI. Furthermore, cHCC-CCAs with MVI may have worse surgical outcomes with regard to early recurrence than those without MVI.
Key Points
• Higher serum levels of AFP combined with irregular arterial peritumoral enhancement are independent risk factors for the MVI of cHCC-CCA, while fat deposition might be a protective factor.
• cHCC-CCA with MVI may have a higher risk of early recurrence after surgery.
• Most cHCC-CCAs were categorized as LR-M in this study, and no significant difference was found in MVI based on LI-RADS category.
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models ...as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies.
► PlGF inhibition phenocopies genetic deficiency in tumor models and ocular angiogenesis ► PlGF inhibition blocks vessel abnormalization rather than density in certain tumors ► Anti-mouse and anti-human PlGF antibodies are specific and efficacious ► Anti-PlGF treatment lacks efficacy in some cancer models
IMPORTANCE: Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly ...lasting effects of methylphenidate on the human dopaminergic system. OBJECTIVES: To determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain–Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment–naive status. INTERVENTIONS: Treatment with either methylphenidate or a matched placebo for 16 weeks. MAIN OUTCOMES AND MEASURES: Change in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses. RESULTS: Among 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7-14.8; P = .03). CONCLUSIONS AND RELEVANCE: We confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up. TRIAL REGISTRATION: identifier: NL34509.000.10 and trialregister.nl identifier: NTR3103.
Anatomy of the Vascularized Lateral Femoral Condyle Flap Parvizi, Daryousch; Vasilyeva, Anna; Wurzer, Paul ...
Plastic and reconstructive surgery (1963),
2016-June, 2016-Jun, 2016-06-00, 20160601, Letnik:
137, Številka:
6
Journal Article
Recenzirano
BACKGROUND:The perforators of the free lateral femoral condyle flap have yet to be adequately described in humans. Therefore, the authors investigated the perforator vessels of the lateral femoral ...condyle flap in an anatomical study and discussed potential clinical applications with a particular interest in its indication with vascularized bone and/or iliotibial band for tendon repair surgery.
METHODS:The authors dissected thighs of 28 cadavers to evaluate the anatomical properties of perforator vessels that branch from the superior lateral genicular artery and supply bone, cartilage, subcutaneous tissue, and the iliotibial band of the lateral femoral condyle.
RESULTS:In each dissected thigh, the superior lateral genicular artery was present and the average pedicle length was 38 ± 10 mm. The average diameter of the superior lateral genicular artery, proximal to its distribution into the deep articular and superficial patellar branches, was 2 ± 0.5 mm. A communication between deep articular and superficial patellar branches was seen in 96 percent of the dissected thighs. In 24 cases (86 percent), the authors were able to show the iliotibial band perforating vessel and harvest a free lateral femoral condyle flap as an osteochondral fasciocutaneous bone flap with vascularized tendon.
CONCLUSIONS:Altogether, the authors’ results indicate that the blood supply of the lateral femoral condyle flap is consistent and the lateral femoral condyle flap could serve as a free composite flap for complex indications in hand or limb reconstructive surgery. Clinical studies to compare the lateral femoral condyle to other well-established microsurgical free flaps are warranted.
Functional connectomics from resting-state fMRI Smith, Stephen M; Vidaurre, Diego; Beckmann, Christian F ...
Trends in cognitive sciences,
12/2013, Letnik:
17, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Highlights • Spontaneous fluctuations in brain activity reflect functional brain networks. • We review rfMRI for mapping the functional connectome. • We review methods for functional connectomics ...network analysis. • We describe the WU–Minn Human Connectome Project. • We present exciting new analyses using the latest-released HCP data.
Highlights • Sonography of the peripheral nervous system reveals multifocal nerve enlargement in the majority of chronic inflammatory demyelinating polyneuropathy (CIDP) patients. • Sonographic nerve ...enlargement in CIDP is related with clinical severity. • Increased nerve vascularization, a possible marker for diseases activity, can be detected in CIDP, especially in enlarged nerves.
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