Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinal vascular occlusions are occlusion of the R.C.A. or of the branches with a dramatic loss of the visual function immediately; occlusion of R.C.V. or of the branches, less dramatic at once but a follow up is necessary for a long time because of neovascular complications or macular edema; the most frequent aetiology is also the atherosclerosis. The treatment is the treatment of atherosclerosis or of a particular aetiology. Treatment of the ischemic syndrome is supported by Argon laser for retinal photocoagulation.
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PMID:[Retinal vascular occlusions]. 273 79

In patients with diabetic nephropathy retinopathy is always present and proliferative retinopathy is common. Retinopathy tends to deteriorate as renal failure develops particularly in patients with poorly controlled blood pressure and in patients in whom no retinal treatment has been given before development of renal failure. Treatment of hypertension and of end stage renal failure will improve macular edema and stabilize vision. As the progression of diabetic retinopathy is independent of diabetic nephropathy and not reversed by treatment of nephropathy, further follow-up and treatment of diabetic retinopathy are imperative. In recent years medical treatment of arterial hypertension and facilities for dialysis and kidney transplantation have become available, and patients are now treated at a much earlier stage of their renal disease. Consequently, were are seeing fewer patients with renal failure and severe hypertensive fundus changes. Nevertheless, arterial hypertension is still a very important problem in diabetic patients with and without nephropathy and complications of atherosclerosis are common as a result of chronic hypertension and hyperlipidemia.
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PMID:[Eye fundus of the diabetic patient with nephropathy and hypertensive retinopathy. Macroangiopathic complications]. 858 Dec 31

Many types of adverse ocular reactions to oral contraceptives (OCs) have been reported, but the role of OCs has not always been confirmed. Neuroophthalmologic complications may result from cerebral vascular accidents responsible for visual field deficits, accidents affecting the cerebral trunk, ischemic accidents resulting from obstruction of the internal carotid artery. The role of OCs in cerebral vascular accidents is controversial. Most reports concern older formulations containing high doses of estrogen. In the current state of knowledge it is generally agreed that OCs may induce an increased thromboembolic risk in women over 35, those who smoke, and those with risk factors for atherosclerosis. It is agreed that occurrence of a transient ischemic cerebral vascular accident requires immediate termination of OC use. OCs have been implicated occasionally in retrobulbar optic neuropathy, but the condition in young women appears more likely to be the 1st manifestation of a sclerosis. OCs appear to increase the incidence of benign intracranial hypertension, manifested by headaches, papillary edema endangering the optic nerve, and the absence of visible anomalies on the scanner. It is also recognized that migraines are induced or aggravated by OCs. Migraines are known to be linked to hormonal factors. Ophthalmic migraines belong to the subgroup of vascular migraines. Retinal vascular diseases such as occlusion of the central retinal artery, intraocular hemorrhage, and more rarely macular edema have been reported retrospectively but their documentation has been insufficient to permit determination of causality. The prognosis for retinal emboli is mediocre. Problems in color vision initially affecting blue have been described in OC users and may be a function of the duration of use. The condition is especially prevalent in diabetes. Pregnancy appears to accelerate the loss of visual field in some women with pigmentary retinopathy. For that reason some ophthalmologists recommend that they avoid OCs. Other ocular problems have been observed in OC users but no link has been proven and the only evidence is anecdotal. It has been suggested that OCs decrease tolerance for contact lenses, but prospective studies have not demonstrated a link. All contraindications to OC use should be scrupulously respected. Use should be terminated immediately in case of transient ischemic accident, appearance of sudden severe headaches, vertigo, or vision problems such as papillary edema or retinal hemorrhage.
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PMID:[Adverse ocular reactions to oral contraceptive use]. 1231 84

The main cause of oedematous branch retinal vein occlusion (BRVO) vision loss is macular oedema persistence. We studied 18 patients having oedematous branch retinal vein occlusion. An ophthalmologic exam completed with angiography and etiologic assessment were performed. Argon Laser macular grid photocoagulation was performed in 11 eyes where macular oedema had persisted for over 3 months with visual acuity under 5/10. In 45% of cases, occlusion interests superotemporal vein. Atherosclerosis risk factors are found in 88% of cases. The course was spontaneously favourable in 39% of cases. Improvement of visual acuity was obtained in 36% of cases treated with laser photocoagulation. Oedematous branch retinal vein occlusion outcome is variable; it can be favourable if veino-veinous anastomosis develops rapidly, or unfavourable with macular edema persistence and decreased visual acuity. In the later case, grid macular phototcoagulation should be performed leading to macular edema regression. So, macular edema secondary to branch retinal vein occlusion can disappear spontaneously and needs laser treatment only if it persists.
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PMID:[Aspects of outcome and therapy of edematous branch retinal vein occlusion]. 1596 64

The investigation was undertaken to study the effect of the pentoxifylline retard dosage form Vasonit on ocular hemodynamics in patients with retinal vein occlusions and non-proliferative diabetic retinopathy (DR). Forty-two patients aged 45 to 75 years, including 20 patients (20 eyes) with retinal vein occlusion in the presence of hypertensive disease and atherosclerosis (Group 1) and 22 patients (44 years) with non-proliferative DR (Group 2), were examined. All the patients received the pentoxifylline retard dosage form Vasonit, 600 mg twice a day, for 2 months. After a course of pentoxifylline therapy, the patients were observed to have improved visual functions, positive clinical changes in the fundus of the eye as a reduction in the frequency and extent of retinal hemorrhages, in the degree of manifestations of macular edema, in the number of retinal microaneurysms and ischemic areas. The results of color Doppler mapping of ocular and orbital vessels are indicative of improved hemodynamics as an increase in the values of blood flow velocity and normalization of blood flow resistance and pulsation indices in the arteries supplying blood to the retina and optic nerve.
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PMID:[Role of pentoxifylline retard dosage forms in the correction of hemodynamic disorders in retinal venous occlusion and diabetic retinopathy]. 1780 53

Central retinal vein occlusion (CRVO) remains one of the most common retinal vascular disorders that may lead to blindness. The etiology is unknown, however, predisposing factors such as hypertension, diabetes, atherosclerosis and hypercoagulable states have all been described. Local ophthalmic illnesses such as open angle glaucoma, ocular trauma and orbital infections have also been suggested as causative. CRVO can be subdivided into two clinical types, ischemic and non-ischemic. The non-ischemic type comprises the milder form of the disease with partial venous obstruction and good visual outcome. Ischemic CRVO is the severe form and is associated with visual loss, because of nearly total retinal vein obstruction and poor perfusion to retina. In addition, patients with ischemic CRVO may end up with additional complications such as neovascular glaucoma that may lead to blindness. Over 90% of CRVO occurs in patients > 65 years. The presenting symptom is a sudden painless mono-ocular decrease in visual acuity which could result from macular edema, ischemia, or intraocular bleeding. Ophthalmoscopic examination reveals macular edema, retinal bleeding (more peripheral), tortuous vein dilatation and swollen disc. Current treatment modalities include systemic use of anticoagulation drugs, local treatments including laser, intravitreal injection of anti-vascular endothelial growth factor and surgery (vitrectomy). This review presents the current therapeutic modalities in CRVO.
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PMID:[Treatment modalities in central retinal vein occlusion]. 2081

Inhibition of lipoprotein-associated phospholipase A2 (Lp-PLA2) has been suggested to be a promising therapeutic strategy for several inflammation-associated diseases, including atherosclerosis, Alzheimer's disease, and diabetic macular edema. Herein, we report the discovery of a novel series of Lp-PLA2 inhibitors constructed on an imidazo[1,2-a]pyrimidine scaffold through a conformational restriction strategy. Structure-activity relationship (SAR) analysis resulted in the identification of several compounds with high potency in vitro and good metabolic stability in liver S9 fractions. Compounds 7c and 14b selected for further exploration in vivo demonstrated excellent pharmacokinetic profiles and exhibited significant inhibitory efficacy in SD rats upon oral dosing.
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PMID:Discovery of a Novel Series of Imidazo[1,2-a]pyrimidine Derivatives as Potent and Orally Bioavailable Lipoprotein-Associated Phospholipase A2 Inhibitors. 2647 45

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising therapeutic target for atherosclerosis, Alzheimer's disease, and diabetic macular edema. Here we report the identification of novel sulfonamide scaffold Lp-PLA2 inhibitors derived from a relatively weak fragment. Similarity searching on this fragment followed by molecular docking leads to the discovery of a micromolar inhibitor with a 300-fold potency improvement. Subsequently, by the application of a structure-guided design strategy, a successful hit-to-lead optimization was achieved and a number of Lp-PLA2 inhibitors with single-digit nanomolar potency were obtained. After preliminary evaluation of the properties of drug-likeness in vitro and in vivo, compound 37 stands out from this congeneric series of inhibitors for good inhibitory activity and favorable oral bioavailability in male Sprague-Dawley rats, providing a quality candidate for further development. The present study thus clearly demonstrates the power and advantage of integrally employing fragment screening, crystal structures determination, virtual screening, and medicinal chemistry in an efficient lead discovery project, providing a good example for structure-based drug design.
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PMID:Structure-Guided Discovery of Novel, Potent, and Orally Bioavailable Inhibitors of Lipoprotein-Associated Phospholipase A2. 2919 67

Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein-associated phospholipase A2 (Lp-PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation-related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp-PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp-PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp-PLA2 have been reported recently, while novel inhibitors were identified through a fragment-based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp-PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp-PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp-PLA2, identify more potent and selective Lp-PLA2 inhibitors, and discover the potential indications of Lp-PLA2 inhibitors.
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PMID:Lipoprotein-associated phospholipase A2: The story continues. 3114 Jun 38

This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.
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PMID:Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab. 3278 36


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