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)

Primary open angle glaucoma (OAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and associated visual field loss. OAG is an emerging disease with increasing costs and negative outcomes, yet its fundamental pathophysiology remains largely undetermined. A major treatable risk factor for glaucoma is elevated intraocular pressure (IOP). Despite the medical lowering of IOP, however, some glaucoma patients continue to experience disease progression and subsequent irreversible vision loss. The scientific community continues to accrue evidence suggesting that alterations in ocular blood flow play a prominent role in OAG disease processes. This article develops the thesis that dysfunctional regulation of ocular blood flow may contribute to glaucomatous optic neuropathy. Evidence suggests that impaired vascular autoregulation renders the optic nerve head susceptible to decreases in ocular perfusion pressure, increases in IOP, and/or increased local metabolic demands. Ischemic damage, which likely contributes to further impairment in autoregulation, results in changes to the optic nerve head consistent with glaucoma. Included in this review are discussions of conditions thought to contribute to vascular regulatory dysfunction in OAG, including atherosclerosis, vasospasm, and endothelial dysfunction.
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PMID:Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma? 1966 39

To evaluate the pharmacological properties of cilostazol (CLZ), we examined its intraocular pressure (IOP) -lowering effect. CLZ is an inhibitor of Type III phosphodiesterase that increases intracellular cyclic AMP levels by restraining platelet aggregation, and has a potential protective effect against atherosclerosis. We attempted to apply it for use as an anti-glaucoma agent; however, the application of CLZ in the ophthalmic field is limited due to its poor water solubility. We attempted to enhance CLZ solubility using 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). The solubility of CLZ increased with increasing HPbetaCD concentrations, and 0.05% CLZ was dissolved in 10% HPbetaCD. Moreover, fine particle suspension of 0.5% CLZ in 5% HPbetaCD (soluble CLZ: ca. 0.027%) were prepared using a Microfluidizer, an impact-type emulsifying comminution device. In an in vitro transcorneal penetration experiment through the rabbit cornea, the CLZ penetration rate was dependent on the CLZ content of the solutions and suspensions. When a 0.05% CLZ ophthalmic solution was instilled into a rabbit eye, the absorption rate constant for CLZ into an aqueous humor was 0.0059+/-0.001 min(-1), and the elimination rate constant was 0.048+/-0.024 min(-1). Also CLZ ophthalmic solutions and fine particle suspension were examined to for their ability to reduce enhanced intraocular pressure (IOP) of rabbits in a darkroom. The instillation of 0.05% CLZ ophthalmic solutions and 0.5% CLZ fine particle suspensions into rabbit eyes reduced the enhanced IOP. These results demonstrate that the instillation of CLZ ophthalmic solutions and fine particle suspensions may represent an effective anti-glaucoma formulation.
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PMID:Preparation of ophthalmic formulations containing cilostazol as an anti-glaucoma agent and improvement in its permeability through the rabbit cornea. 2062 34

Ocular manifestations of carotid artery occlusive disease, when present, warrant further systemic workup including carotid artery Doppler ultrasound scan. Vascular ocular pathology that may indicate underlying carotid artery disease includes amaurosis fugax, retinal emboli, ocular ischemic syndrome, retinal vascular occlusions, and glaucoma. Early atherosclerotic changes, however, may remain undetected with carotid artery Doppler ultrasound scan. Risk factors for atherosclerosis should be assessed, and additional imaging to detect underlying pathophysiology of carotid artery occlusive disease may also be indicated for preventative management. A review of the literature is conducted to determine the association of ocular sequelae with hemodynamically significant carotid artery stenosis. The role of brachial artery flow-mediated dilation as an independent predictor for cardiovascular disease is also discussed.
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PMID:Carotid artery occlusive disease and ocular manifestations: Importance of identifying patients at risk. 2063 Mar 74

Although the majority of patients with glaucoma have elevated intraocular pressure as the presumed etiology for their resultant neuropathy, it is well known that approximately 25% of patients with glaucoma have intraocular pressure within the normal range for their race. These patients may have conditions that facilitate non-pressure related stress to the retina and optic nerve that might directly contribute to their glaucomatous neuropathy and include chronic or intermittent ischemia (i.e atherosclerosis, heart disease, vasospasm, migraine, sleep apnea), altered scleral/optic nerve head morphology that predisposes to glaucomatous stress (i.e myopia); genetic mutations that predispose to glaucoma damage at normal IOP (OPA-1,optineurin, myocilin) and evidence of aberrant immunity that suggests that their glaucoma might be a form of an autoimmune neuropathy (i.e. presumed autoimmune glaucoma). This review provides a critical assessment of the potential role for autoimmunity as an initiating or exacerbating etiology in some patients with glaucoma.
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PMID:The case for autoimmunity in glaucoma. 2080 Nov 14

The aim of the study was to show ocular manifestations in carotid artery occlusive disease, with pathogenesis, diagnostic and therapeutic abilities of this changes. Carotid arteries are the main route by which the blood is supplied to the cerebrum and eyes. Clinical significant carotid artery stenosis is mainly caused by atherosclerosis. Most frequent neurological symptoms are transient ischemic attacks (TIA) and temporary visual loss (amaurosos fugax) are most common ocular symptoms. Other ocular pathologies in fundus examination are retinal embolies, retinal vein occlusion, anterior ischemic optic neuropathy, ocular ischemic syndrome or glaucoma. Most dangerous complications are stroke, blindness, or even patients death. Besides clinical examination the diagnosis is usually confirmed by carotid artery color Doppler ultrasound, magnetic resonance angiography and retinal fluorescein angiography. It is important to refer a patient with suspected or confirmed significant carotid artery stenosis for appropriate evaluation and treatment to a endovascular surgeon.
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PMID:[Ophthalmological complications associated with clinically significant carotid stenosis]. 2278 48

Ocular ischemic syndrome is a rare condition, which is caused by ocular hypoperfusion due to stenosis or occlusion of the common or internal carotid arteries. Atherosclerosis is the major cause of changes in the carotid arteries. Ocular ischemic syndrome is manifested as visual loss, orbital pain and, frequently, changes of the visual field, and various anterior and posterior segment signs. Anterior segment signs include iris neovascularization and secondary neovascular glaucoma, iridocyclitis, asymmetric cataract, iris atrophy and sluggish reaction to light. Posterior eye segment changes are the most characteristic, such as narrowed retinal arteries, perifoveal telangiectasias, dilated retinal veins, mid-peripheral retinal hemorrhages, microaneurysms, neovascularization at the optic disk and in the retina, a cherry-red spot, cotton-wool spots, vitreous hemorrhage and normal-tension glaucoma. Differential diagnosis of ocular ischemic syndrome includes diabetic retinopathy and moderate central retinal vein occlusion. Carotid artery imaging and fundus fluorescein angiography help to establish the diagnosis of ocular ischemic syndrome. The treatment can be local, for example, ocular (conservative, laser and surgical) or systemic (conservative and surgical treatment of the carotid artery). Since the condition does not affect the eyes alone, patients with ocular ischemic syndrome should be referred for consultation to the neurologist, vascular surgeon and cardiologist.
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PMID:Ocular ischemic syndrome - a systematic review. 2284 15

Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SNPs associated with many important human diseases, including diseases associated with aging. In an effort to understand the genetics of broad resistance to age-associated diseases (i.e., 'wellness'), we performed a meta-analysis of human GWAS. Toward that end, we compiled 372 GWAS that identified 1775 susceptibility SNPs to 105 unique diseases and used these SNPs to create a genomic landscape of disease susceptibility. This map was constructed by partitioning the genome into 200 kb 'bins' and mapping the 1775 susceptibility SNPs to bins based on their genomic location. Investigation of these data revealed significant heterogeneity of disease association within the genome, with 92% of bins devoid of disease-associated SNPs. In contrast, 10 bins (0.06%) were significantly (P < 0.05) enriched for susceptibility to multiple diseases, 5 of which formed two highly significant peaks of disease association (P < .0001). These peaks mapped to the Major Histocompatibility (MHC) locus on 6p21 and the INK4/ARF (CDKN2a/b) tumor suppressor locus on 9p21.3. Provocatively, all 10 significantly enriched bins contained genes linked to either inflammation or cellular senescence pathways, and SNPs near regulators of senescence were particularly associated with disease of aging (e.g., cancer, atherosclerosis, type 2 diabetes, glaucoma). This analysis suggests that germline genetic heterogeneity in the regulation of immunity and cellular senescence influences the human healthspan.
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PMID:Review: a meta-analysis of GWAS and age-associated diseases. 2288 63

Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood-brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide recommendations on how to effectively promote the field in order to create innovative diagnostic tools to predict the pathology and develop more efficient treatment approaches tailored to the person.
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PMID:The primary vascular dysregulation syndrome: implications for eye diseases. 2374 77

Among known glaucoma triggers, pseudoexfoliation syndrome (PXF) is most of all studied. Development of open-angle glaucoma (OAG) in some patients with PXF and certain somatic diseases requires further investigation. This study was aimed to evaluation of glaucoma risk in patients with PXF in relation to concurrent somatic pathology. A total of 185 patients aged from 48 to 87 diagnosed with OAG and, additionally, 75 patients of control group were assessed. Complex examination was performed and anamnestic data collected in all cases. A statistically significant relationship between OAG development and the presence of primary hypertension, ischemic heart disease, chronic cerebral circulatory insufficiency, and atherosclerosis in patients with PXF has been established.
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PMID:[Occurrence and characteristics of cardiovascular pathology in patients with pseudoexfoliative glaucoma]. 2462

It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, including an increase in cancer incidence, wrinkling and diminished skin elasticity, atherosclerosis, osteoporosis, weight loss, age-related cataract, glaucoma and others. Shorter telomere length in leukocytes was associated crosssectionally with cardiovascular disorders and their risk factors, including pulse pressure and vascular aging, obesity, vascular dementia, diabetes, coronary artery disease, myocardial infarction (although not in all studies), cellular turnover and exposure to oxidative and inflammatory damage in chronic obstructive pulmonary disease. It has been proposed that telomere length may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging. The data reveal that telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state and in this article these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. In particular, the presence of highly specific correlations and early causal relationships between telomere loss in the absence of telomerase activity and replicative senescence or crisis, and from the other side, telomerase reactivation and cell immortality, point to new and important treatment strategies or the therapeutic manipulation during treatment of age related disorders and cancer. Once better controls and therapeutic treatments for aging and age-related disorders are achieved, cellular rejuvenation by manipulating telomeres and enzyme telomerase activity may reduce some of the physiological declines that accompany aging. In this work, we raise and support a therapeutic concept of using non-hydrolyzed forms of naturally occurring imidazoledipeptide based compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur with the demonstrated evidence of telomere shortening appeared to be a hallmark of oxidative stress and disease. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival and an advanced oral nutritional support with non-hydrolyzed carnosine (or carcinine and patented compositions thereof) and patented N-acetylcarnosine lubricant eye drops are useful therapeutic tools of a critical telomere length maintenance that may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolong life expectancy, increase survival and chronological age of an organism in health control, smoking behavior and disease.
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PMID:Oxidative damage impact on aging and age-related diseases: drug targeting of telomere attrition and dynamic telomerase activity flirting with imidazole-containing dipeptides. 2489 99


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