Dermal filler complications and management
Michael Parker in Fundamentals for Cosmetic Practice, 2022
The complications of dermal filler augmentation are much more widely publicised than those of botulinum toxin therapy. Avascular necrosis is the term used to describe cell death secondary to a lack of oxygenated blood. In the context of dermal filler augmentation, there are two main mechanisms in which avascular necrosis can occur: first, it may be caused by direct injection of dermal filler into an artery, and second, it may due to a local pressure effect of the filler itself pressing on an artery from the outside. Hyaluronidase is an enzyme which dissolves hyaluronic acid, the key constituent in most dermal fillers. It needs to be injected directly into the area suspected of being devoid of arterial blood supply. Aspirin prevents platelet aggregation and prevents blood clotting by inhibiting thromboxane A2. Within the first few hours after a venous occlusive event, patients may notice an area of progressive swelling associated with a dull ache.
Eicosanoids and the Regulation of Uteroplacental Hemodynamics
Murray D. Mitchell in Eicosanoids in Reproduction, 2020
The metabolites of arachidonic acid are often referred to as “eicosanoids” because of the chemical name for the substrate is eicosatetraenoic acid. Arachidonate metabolism by the cyclooxygenase pathway leads to the formation of prostaglandins (PGs) and thromboxane. The effects of PGs on the pregnant uteroplacental vasculature have been evaluated mainly in chronically instrumented sheep; however, studies also have been performed in the pregnant canine, rabbit, and human. Numerous studies have been performed in an attempt to delineate the vascular effects of the various PGs on the uterine vascular bed. The effects of PGs on the pregnant uteroplacental vasculature have been evaluated mainly in chronically instrumented sheep; however, studies also have been performed in the pregnant canine, rabbit, and human. Studies which have examined venous-arterial concentration differences of PGs across the gravid uterus and/or urinary concentrations of prostanoids have yielded valuable information pertaining to local and total systemic production of the PG compounds.
Arteropathies, Microcirculation and Vasculitis
Mary N. Sheppard in Practical Cardiovascular Pathology, 2022
The endothelium plays a pivotal role in regulating vascular blood flow via complex autoregulatory processes, mediating smooth muscle relaxation and constriction within the microcirculation through molecules such as nitric oxide, prostacyclins, thromboxane A1 and endothelin-1 (ET-1). The diffuse nature of small-vessel disease is indicated by increased peripheral small artery contractility to ET-1 from gluteal biopsy samples in patients with microvascular angina. Giant cell arteritis is the commonest vasculitis affecting patients over 50 years of age who develop a high erythrocyte sedimentation rate. The intimal proliferation in restenosis lesions is histologically the same as in transplant arteriopathy and the hyperplastic form of arteriolosclerosis. Monckeberg's medial calcific sclerosis is linear calcification, usually at the internal elastic lamina. Adventitial cystic disease is a variant of ganglionic cyst in which the cyst extends along the vessel wall adventitia. Intravascular papillary endothelial hyperplasia can mimic vascular neoplasms such as angiosarcoma.
Effects of Thromboxane Synthase Inhibition on Placental Prostacyclin and Thromboxane Production
Published in Clinical and Experimental Hypertension. Part B: Hypertension in Pregnancy, 1990
Selective inhibition of thromboxane synthesis without affecting prostacyclin synthesis is being considered as a potential treatment for preeclampsia because of its imbalance of increased thromboxane/decreased prostacyclin production. Thromboxane production by the placenta is greatly increased in preeclampsia so effective therapy must inhibit placental, as well as maternal platelet, thromboxane production. The following study was done to evaluate the production rates of thromboxane and prostacyclin in placental tissues incubated with and without the throraboxane synthase inhibitor, U-63,557A. Fresh, human term placental tissues (350 mg) were incubated in a sterile manner in 7 ml Dulbecco's Modified Eagle's Medium for 48 hours at 37°C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 0, 8, 20, 32 and 48 hours and analyzed for thromboxane A2 by radioimmunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F1a. Addition of U-63,557A, 0.1 μM, significantly decreased (P < 0.001) thromboxane production in both preeclamptic (n=6) and normal placentas (n=5). Placental prostacyclin production was not affected (P>0.6) by addition of U-63,557A in either normal or preeclamptic placentas. The placental production rate ratios of thromboxane to prostacyclin were significantly higher for preeclampsia than for normal pregnancy, and addition of U-63,557A to preeclamptic tissue reduced the thromboxane/prostacyclin ratios to those of normal placental tissue. Therefore, inhibition of placental thromboxane synthase results in selective inhibition of thromboxane synthesis without affecting placental prostacyclin synthesis, and it can restore the increased ratio of thromboxane to prostacyclin of preeclampsia to that of normal pregnancy.
Progestogens reduce thromboxane production by cultured human endothelial cells
Published in Climacteric, 2011
P. J. Oviedo, A. Sobrino, S. Novella, C. Rius, A. Laguna-Fernandez, M. A. García-Pérez, J. J. Tarín, A. Cano, C. Hermenegildo
Objectives Progestogens have been poorly studied concerning their roles in endothelial physiology. Prostanoids are vasoactive compounds, such as thromboxane A2, a potent vasoconstrictor, and prostacyclin, a vasodilator. We examined the effects of two progestogens used clinically, progesterone and medroxyprogesterone acetate, on thromboxane A2 production by cultured human umbilical vein endothelial cells (HUVEC) and investigated the role of progesterone receptors and the enzymes involved in production of thromboxane A2 and prostacyclin. Methods Cells were exposed to 1–100 nmol/l of either progesterone or medroxyprogesterone acetate, and thromboxane A2 production was measured in culture medium by enzyme immunoassay. Gene expression of prostacyclin synthase and thromboxane synthase was analyzed by quantitative real-time polymerase chain reaction. Expression of prostacyclin synthase protein was analyzed by Western blot. Results Both progestogens decreased thromboxane A2 release after 24 h. Protein and gene expression of prostacyclin synthase were increased after exposure to both progestogens, without changes in thromboxane synthase expression. These effects induced by progestogens were mediated through progesterone receptors, since they were decreased in the presence of the progesterone receptor antagonist RU486. The cyclo-oxygenase-1 selective inhibitor reduced thromboxane release. Conclusion Progesterone and medroxyprogesterone acetate decreased HUVEC thromboxane release in a progesterone receptor-dependent manner, without changes in thromboxane synthase expression and enhanced prostacyclin synthase gene and protein expression.
Antagonism of P2Y
Published in Platelets, 2010
Kamala Bhavaraju, Alexander Georgakis, Jianguo Jin, Theodore Kent Gartner, Yoshiaki Tomiyama, Alan Nurden, Paquita Nurden, Satya P. Kunapuli
Antiplatelet therapy for the management of patients with cardiovascular risks often includes a combination therapy of aspirin and clopidogrel, acting through inhibition of thromboxane generation and blockade of Gi-coupled P2Y12 receptor, respectively. We hypothesized that ADP acting through P2Y12 regulates physiological thromboxane levels. The serum thromboxane levels in mice (n = 3) dosed with clopidogrel and prasugrel were decreased by 83.1 ± 5.3% and 94.26 ± 1.75% respectively compared to untreated mice. Pre-treatment of human blood (n = 3) ex vivo with active metabolites of clopidogrel or prasugrel led to a reduction in thromboxane levels to 16.3 ± 3.2% and 4.9 ± 0.8% respectively, compared to untreated human serum. We also evaluated serum thromboxane levels in P2Y receptor null mice (n = 4). Whereas serum thromboxane levels in P2Y1 null mice were similar to those in wild type littermates, those in the P2Y12 null mice were inhibited by 83.15 ± 3.8%. Finally, in a pilot study, serum thromboxane levels were reduced by 76.05 ± 8.41% in healthy human volunteers (n = 6) upon dosing with clopidogrel, compared to the levels before dosing. In conclusion, P2Y12 antagonism alone can decrease physiological thromboxane levels. Thus, this study could pave way the for newer/modified treatment regimens for the management of patients with thrombotic complications who are allergic or non-responsive to aspirin.
Related Knowledge Centers
- Eicosanoid
- Lipid
- Thrombosis
- Thromboxane A2