Project description:Two melanotic human melanoma cell lines, IRE 1 and IRE 2, and the lymphoma- and leukaemia-derived cell lines Raji and K 562, were exposed to different concentrations (from 5 X 10(-3) M to 10(-5) M) of phenols, both substrates (s) and non-substrates (ns) of tyrosinase, in the presence or absence of the oxygen-radical-scavenger enzymes superoxide dismutase, catalase and peroxidase. Monophenols were tyrosine (s), 4-hydroxyanisole (s) and butylated hydroxyanisole (ns); diphenols were L-3,4-dihydroxyphenylalanine (s), dopamine (3,4-dihydroxyphenethylamine) (s), terbutylcatechol (s), hydroquinone (s) and resorcinol (ns); triphenols were 6-hydroxydopa (3,4,6-trihydroxyphenylalanine) (s) and methyl gallate (s). Triphenols and o- and p-diphenols underwent complete oxidation in culture medium within 24 h of incubation and were significantly more toxic than monophenols and the m-diphenol resorcinol, which, under the same cultural conditions, were much more stable. No significant differences in percentage survival were found among the different cell lines for each drug tested. The major component of toxicity up to 24 h of di- and tri-phenols is due to toxic oxygen species acting outside the cells and not to cellular uptake of these phenols as such. In fact the addition of oxygen-radical-scavenger enzymes significantly (P less than 0.01) decreased the adverse effect of these drugs on all cell lines. The lower toxicity of monophenols and resorcinol as compared with that of di- and tri-phenols is due, in our opinion, to the fact that they are less oxidized under the conditions existing in the culture medium, and therefore do not produce sufficient levels of oxygen radicals. For these compounds, a primary intracellular action has to be taken into account to explain their cytotoxicity.
Project description:Objective: Vascular malformations affect 3% of neonates. Venous malformations (VMs) are the largest group representing more than 50 % of cases. In hereditary forms of VMs gene mutations have been identified, but for the large group of spontaneous forms the primary cause and downstream dysregulated genes are unknown. Methods and Results: We have performed a global comparison of gene expression in slow-flow VMs and normal saphenous veins using human whole genome micro-arrays. Genes of interest were validated with qRT-PCR. Gene expression in the tunica media was studied after laser micro-dissection of small pieces of tissue. Protein expression in endothelial cells (ECs) was studied with antibodies. We detected 511 genes more than 4-fold down- and 112 genes more than 4-fold up-regulated. Notably, chemokines, growth factors, transcription factors and regulators of extra-cellular matrix (ECM) turnover were regulated. We observed activation and arterialization of ECs of the VM proper, whereas ECs of vasa vasorum exhibited up-regulation of inflammation markers. In the tunica media, an altered ECM turnover and composition was found. Conclusions: Our studies demonstrate dysregulated gene expression in tunica interna, media and externa of VMs, and show that each of the three layers represents a reactive compartment. The dysregulated genes may serve as therapeutic targets. Keywords: disease analysis
Project description:Importance:Congenital retinal macrovessel (CRM) is a rarely reported venous malformation of the retina that is associated with venous anomalies of the brain. Objective:To study the multimodal imaging findings of a series of eyes with congenital retinal macrovessel and describe the systemic associations. Design, Setting, and Participants:In this cross-sectional multicenter study, medical records were retrospectively reviewed from 7 different retina clinics worldwide over a 10-year period (2007-2017). Patients with CRM, defined as an abnormal, large, macular vessel with a vascular distribution above and below the horizontal raphe, were identified. Data were analyzed from December 2016 to August 2017. Main Outcomes and Measures:Clinical information and multimodal retinal imaging findings were collected and studied. Pertinent systemic information, including brain magnetic resonance imaging findings, was also noted if available. Results:Of the 49 included patients, 32 (65%) were female, and the mean (SD) age at onset was 44.0 (20.9) years. A total of 49 eyes from 49 patients were studied. Macrovessel was unilateral in all patients. Color fundus photography illustrated a large aberrant dilated and tortuous retinal vein in all patients. Early-phase frames of fluorescein angiography further confirmed the venous nature of the macrovessel in 40 of 40 eyes. Optical coherence tomography angiography, available in 17 eyes (35%), displayed microvascular capillary abnormalities around the CRM, which were more evident in the deep capillary plexus. Of the 49 patients with CRM, 39 (80%) did not illustrate any evidence of ophthalmic complications. Ten patients (20%) presented with retinal complications, typically an incidental association with CRM. Twelve patients (24%) were noted to have venous malformations of the brain with associated magnetic resonance imaging. Of these, location of the venous anomaly in the brain was ipsilateral to the CRM in 10 patients (83%) and contralateral in 2 patients (17%), mainly located in the frontal lobe in 9 patients (75%). Conclusions and Relevance:Our study has identified an association between macrovessels in the retina and venous anomalies of the brain (24% compared with 0.2% to 6.0% in the normal population). Thus, we recommend new guidelines for the systemic workup of patients with CRM to include brain magnetic resonance imaging with contrast. These lesions may be more accurately referred to as retinal venous malformations, which may raise awareness regarding potential cerebral associations.
Project description:Background and purposeA number of studies have demonstrated the existence of segmental vascular disorders affecting soft tissues of the head and neck along with the intracranial vasculature. The purpose of this study was to determine whether there is an association between cerebral developmental venous anomalies and venous malformations of the face, head, and neck.Materials and methodsA consecutive series of patients with head and neck venous malformations who underwent MR imaging of the brain with postcontrast T1- or T2*-weighted imaging were included. Developmental venous anomaly prevalence in this patient population was compared with an age- and sex-matched control group without venous malformations at a ratio of 1:2. All images were interpreted by 2 neuroradiologists. Data were collected on venous malformation location, developmental venous anomaly location, developmental venous anomaly drainage pattern, and metameric location of venous malformations and developmental venous anomalies. Categoric variables were compared using χ2 tests.ResultsForty-two patients with venous malformations were included. The mean age was 38.1 ± 11.1 years, and 78.6% of patients were female. The prevalence of developmental venous anomalies in this patient population was 28.6%. The control population of 84 patients had a mean age of 40.0 ± 5.9 years, and 78.6% of patients were female. The prevalence of developmental venous anomalies in this patient population was 9.5% (P = .01). In 83.3% of cases, developmental venous anomalies were ipsilateral to the venous malformation, and in 75% of cases, they involved the same metamere.ConclusionsOur case-control study demonstrated a significant association between brain developmental venous anomalies and superficial venous malformations. These findings suggest that there may be a similar pathophysiologic origin for these 2 entities.
Project description:Objective: Vascular malformations affect 3% of neonates. Venous malformations (VMs) are the largest group representing more than 50 % of cases. In hereditary forms of VMs gene mutations have been identified, but for the large group of spontaneous forms the primary cause and downstream dysregulated genes are unknown. Methods and Results: We have performed a global comparison of gene; expression in slow-flow VMs and normal saphenous veins using human whole genome micro-arrays. Genes of interest were validated with qRT-PCR. Gene expression in the tunica media was studied after laser micro-dissection of small pieces of tissue. Protein expression in endothelial cells (ECs) was studied with antibodies. We detected 511 genes more than 4-fold down- and 112 genes more than 4-fold up-regulated. Notably, chemokines, growth factors, transcription factors and regulators of extra-cellular matrix (ECM) turnover were regulated. We observed activation and arterialization of ECs of the VM proper, whereas ECs of vasa vasorum exhibited up-regulation of inflammation markers. In the tunica media, an altered ECM turnover and composition was found. Conclusions: Our studies demonstrate dysregulated gene expression in tunica interna, media and externa of VMs, and show that each of the three layers represents a reactive compartment. The dysregulated genes may serve as therapeutic targets. Experiment Overall Design: - 4 samples Experiment Overall Design: - samples are replicates with dye swap
Project description:A 50-year-old woman who had previously undergone right radical mastectomy presented with chest tightness and shortness of breath after physical activities. A cardiac mass and multiple hepatic lesions were successively detected. We first performed hepatic puncture biopsy. Histopathologic examination confirmed that the multiple hepatic lesions were venous malformations. Based on the imaging findings and previous reports in the literature, we boldly speculated that the cardiac mass was also a venous malformation. The cardiac venous malformation was successfully resected, and the postoperative pathology confirmed our suspicion.
Project description:BackgroundA reliable venous thromboembolism (VTE) risk assessment model (RAM) can assist surgeons in identifying patients who would benefit from VTE prophylaxis. This systematic review was aimed at summarising the current available evidence on VTE RAMs used in aesthetic plastic surgery.MethodsA comprehensive search was performed in the PubMed, EMBASE and Cochrane databases to include primary studies describing VTE RAMs in aesthetic plastic surgery from 1946 to February 2019. The objective was to compare the different VTE RAMs described for aesthetic plastic surgery to recommend a reliable model to stratify patients.ResultsOf the 557 articles identified in the PubMed, EMBASE and Cochrane databases, six articles were included in the final review. Five different RAMs were used in the included studies: Caprini 2005 RAM, Caprini 2010 RAM, Davison-Caprini 2004 RAM, the American Society of Anaesthesiologist's (ASA) physical status grading system and a tool developed by Wes et al. The difference in risk weightage amongst the tools along with the VTE incidences for different categories was compared. The Caprini 2005 RAM was the most widely reported tool and validated in plastic surgery patients.ConclusionAmongst the five different tools currently used, the Caprini 2005 RAM was the most widely reported. This tool was validated in plastic surgery patients and reported to be a sensitive and reliable tool for VTE risk stratification; therefore, current data support its use until further higher quality evidence becomes available. Because of the heterogeneity of the data and low quality of the current evidence, a definitive recommendation cannot be made on the best VTE RAM for patients undergoing aesthetic plastic surgery. This paper highlights the need for randomised controlled trials evaluating the various RAMs which are essential to support future recommendations and guidelines.
Project description:OBJECTIVE: To determine which venous malformations (VMs) are at risk for coagulopathy. Venous malformations are slow-flow vascular malformations present at birth, and localized intravascular coagulopathy (LIC) causes pain and thrombosis within a lesion and severe bleeding during surgical procedures. DESIGN: Prospective convenience sample accrued from 2 multidisciplinary sites in Brussels, Belgium, and Caen, France. PARTICIPANTS: The study population comprised 140 patients with clinical data and coagulation parameters. Magnetic resonance imaging was performed for 110 patients. MAIN OUTCOME MEASURE: Measurement of D-dimer levels. RESULTS: Of the 140 participants, 59 (42%) showed high D-dimer levels, 36 (61%) of whom had levels higher than 1.0 microg/mL. Six of the participants had low fibrinogen levels. In univariate analysis, large surface, presence of palpable phleboliths, and truncal localization were associated with high D-dimer levels. In the multivariate analysis, only large surface area and presence of phleboliths remained independently associated with high D-dimer levels. Severe LIC, characterized by concomitant low fibrinogen level, was associated with extensive venous malformations of the extremities. CONCLUSIONS: Localized intravascular coagulopathy is statistically significantly associated with large and/or deep venous malformations that affect any location, which can have a palpable phlebolith. These patients are at risk of local pain due to thrombosis. Lesions with elevated D-dimer levels associated with low fibrinogen levels (severe LIC) commonly affect an extremity and have a high risk of hemorrhage. Low-molecular-weight heparin can be used both to treat the pain caused by LIC and to prevent decompensation of severe LIC to disseminated intravascular coagulopathy.