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 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomere length is emerging as a biomarker for aging and survival is paternally inherited and associated with parental lifespan. 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 cross-sectionally with cardiovascular disorders and its 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. Effective regulation of abnormal therapeutic targets of an age-related disease requires the alteration of either the topological structure or dynamic characteristics of telomeres which are DNA-protein structures at the ends of eukaryotic chromosomes, the DNA of which comprise noncoding repeats of guanine-rich sequences. Telomeric DNA plays a fundamental role in protecting the cell from recombination and degradation, including those as the metabolic super-achievers in the body, organ systems in a given target network of a disease and aging. In order to manage and control the complex direct and indirect target hubs, in this paper, a review of the recent patents is made analyzing techniques, new approaches developed during the last years in adaptive pharmacology directed at slowing and preventing the loss of telomere length that may slow aging using pharmaceutical and nutritional module-based designs, such as with regard to the timing of administration of imidazole-containing dipeptides. We discuss our recent identification of the role of neuron-specific imidazole- containing dipeptide based compounds (L-carnosine, N-acetylcarnosine, carcinine) that regulate and therapeutically control telomere shortening, telomerase activity and cellular senescence. We support a therapeutic concept of using nonhydrolyzed forms of naturally occurring imidazole-dipeptide 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 pharmaconutrition provision with non-hydrolyzed carnosine (or carcinine and patented compositions thereof) is a useful therapeutic tool of a critical telomere length maintenance (allowing indirectly to manipulate with telomerase activity) that may fundamentally be applied in the therapeutic treatment of agerelated sight-threatening eye disorders, Diabetes mellitus, sarcopenia (that is the gradual loss of muscle mass) that can affect elderly people and subjects under the effect of exhausting exercises and physical load, prolong life expectancy, increase survival and chronological age of an organism in health control, smoking behavior, metabolic syndrome increasing the risk of developing cardio-vascular diseases, age-related neurodegenerative diseases, including Alzheimer's disease and cognitive impairment.
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PMID:Novel neuroendocrine and metabolic mechanism provides the patented platform for important rejuvenation therapies: targeted therapy of telomere attrition and lifestyle changes of telomerase activity with the timing of neuron-specific imidazole-containing dipeptide-dominant pharmaconutrition provision. 2491 Feb 83

The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.
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PMID:Flammer syndrome. 2507 28

Pseudoexfoliation (PEX) syndrome is a well-recognized late-onset disease caused by a generalized fibrillopathy. It is linked to a broad spectrum of ocular complications including glaucoma and perioperative problems during cataract surgery. Apart from the long-known intraocular manifestations, PEX deposits have been found in a variety of extraocular locations and they appear to represent a systemic process associated with increased cardiovascular and cerebrovascular morbidity. However, as published results are inconsistent, the clinical significance of the extraocular PEX deposits remains controversial. Identification of PEX deposits in the heart and the vessel wall, epidemiologic studies, as well as, similarities in pathogenetic mechanisms have led to the hypothesis of a possible relation between fibrillar material and cardiovascular disease. Recent studies suggest that PEX syndrome is frequently linked to impaired heart and blood vessels function. Systemic and ocular blood flow changes, altered parasympathetic vascular control and baroreflex sensitivity, increased vascular resistance and decreased blood flow velocity, arterial endothelial dysfunction, high levels of plasma homocysteine and arterial hypertension have all been demonstrated in PEX subjects. Common features in the pathogenesis of both atherosclerosis and PEX, like oxidative stress and inflammation and a possible higher frequency of abdominal aorta aneurysm in PEX patients, could imply that these grey-white deposits and cardiovascular disorders are related or reflect different manifestations of the same process.
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PMID:Pseudoexfoliation syndrome and cardiovascular diseases. 2522 63

Homocysteine (Hcy) is a derived sulfur-containing and non-proteinogenic amino acid. The metabolism of Hcy occurs either through the remethylation to methionine or transsulfuration to cysteine. Studies have identified hyperhomocysteinemia (HHcy) as one of the possible risk factors for a multitude of diseases including vascular, neurodegenerative and ocular diseases. Association of HHcy with eye diseases such as retinopathy, pseudoexfoliative glaucoma maculopathy, cataract, optic atrophy and retinal vessel atherosclerosis is established. The molecular mechanism underlying these ocular diseases has been reported as impaired vascular endothelial function, apoptosis of retinal ganglion cells, extracellular matrix alterations, decreased lysyl oxidase activity and oxidative stress. The formed homocysteine-thiolactone in HHcy has stronger cytotoxicity and pro-inflammatory properties which can induce lens opacification and optic nerve damage. The metabolism of Hcy requires enzymes with vitamins such as folic acid, vitamins B12 and B6. Despite the mixed conclusion of various studies regarding the level of these vitamins in elder people, studies recommended the treatment with folate and B12 to reduce Hcy levels in subjects with or without any defect in the enzymes involved in its metabolism. The levels of Hcy, folate, B6 as well as B12 should be measured early in patients with visual impairment that would aid to screen patients for life-threatening disorders related with HHcy. Elder patients may supplement with these vitamins in order to attenuate the ocular damages. This article discusses the association of Hcy in ocular diseases and the possible mechanism in the pathogenesis.
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PMID:Homocysteine in ocular diseases. 2634 24

Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis. Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies. Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects. The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer. Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.
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PMID:Cannabinoid pharmacology in cancer research: A new hope for cancer patients? 2685 55

Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)-Tie system is a second endothelial cell specific ligand-receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang-Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang-Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang-Tie system in vascular development and pathogenesis of vascular diseases.
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PMID:Angiopoietin-Tie signalling in the cardiovascular and lymphatic systems. 2794 Nov 61

The endothelium has increasingly been recognized as a smart barrier and a key regulator of blood flow in micro- and macrovascular beds. Endothelial dysfunction marks a stage of atherosclerosis and is an important prognostic marker for cardiovascular disease. Yet, some people who tend to be slim and physically active and with rather low blood pressure show a propensity to respond to certain stimuli such as emotional stress with endothelial-mediated vascular dysregulation (Flammer syndrome). This leads to characteristic vascular symptoms such as cold hands but also a risk for vascular-mediated diseases such as normal-tension glaucoma. It is the aim of this review to delineate the differences between Flammer syndrome and its "counterpart" endothelial dysfunction in the context of cardiovascular diseases.
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PMID:Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences. 2882 36

More than 26 million Americans suffer with cataracts, and with 3.6 million cataract extractions performed annually in the United States, it is the most common surgical procedure. The integrity of the delicate structures of the eye that mediate vision is dependent on the intraocular pressure (IOP). Yet, IOP acts to compress the vessels within the globe-akin to a Starling resistor-and is a key component that determines the ocular perfusion pressure, defined as the difference between arterial pressure and IOP. The retina is one of the most metabolically active tissues in the body, and its functional integrity is dependent on an adequate blood supply, with retinal function linearly related to the ocular perfusion pressure. Retinal cell death has been demonstrated at low perfusion pressures (below 50 mm Hg). Modern ophthalmic surgery involves globe irrigation, manipulation, and instrumentation, resulting in dynamic pressure fluxes within the eye. Marked elevations of IOP (up to 4-5 times the normal value) with consequent borderline retinal and optic disk perfusion pressures occur for prolonged periods during many ophthalmic procedures. General surgeries, including laparoscopic, spinal, and cardiac procedures, especially, with their demand for steep Trendelenburg or prolonged prone positioning and/or hypotensive anesthesia, can induce IOP changes and ocular perfusion imbalance. These rapid fluctuations in IOP, and so in perfusion, play a role in the pathogenesis of the visual field defects and associated ocular morbidity that frequently complicate otherwise uneventful surgeries. The exact etiology of such outcomes is multifactorial, but ocular hypoperfusion plays a significant and frequently avoidable role. Those with preexisting compromised ocular blood flow are especially vulnerable to intraoperative ischemia, including those with hypertension, diabetes, atherosclerosis, or glaucoma. However, overly aggressive management of arterial pressure and IOP may not be possible given a patient's comorbidity status, and it potentially exposes the patient to risk of catastrophic choroidal hemorrhage. Anesthetic management significantly influences the pressure changes in the eye throughout the perioperative period. Strategies to safeguard retinal perfusion, reduce the ischemic risk, and minimize the potential for expulsive bleeding must be central to the anesthetic techniques selected. This review outlines: important physiological principles; ophthalmic and general procedures most likely to develop damaging IOP levels and their causative factors; the effect of anesthetic agents and techniques on IOP; recent scientific evidence highlighting the significance of perfusion changes during surgery; and key aspects of postoperative visual loss and management approaches for high-risk patients presenting for surgery.
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PMID:Physiology and Role of Intraocular Pressure in Contemporary Anesthesia. 2904 74

Hyperhomocysteinemia is a risk factor for atherosclerosis, which may also be associated with retinal vascular disease, diabetic retinopathy, retinal vein occlusion, and glaucoma. For this study, we established a hyperhomocysteinemia animal model to explore homocysteine (hcy)-related choroidal angiogenesis and possible related factors. We injected Sprague Dawley (SD) rats with different concentrations of hcy and performed color fundus imaging, fluorescein angiography, image-guided optical coherence tomography, and retinal histology to observe the retinal and choroidal changes. Subsequently, we observed prominent choroidal vasculature with congested and tortuous retinal and choroidal vessels in fundus angiographies of the hyperhomocysteinemia animal model. In the histological study, the choroidal capillaries proliferated in the hcy-treated eyes, mimicking choroidal neovascularization. Disrupted retinal pigment epithelium (RPE), abnormal branching vascular network (BVN), and polyp-like structures were also observed in the hcy-treated eyes. Furthermore, we found that placental growth factor (PlGF), but not vascular epithelial growth factor (VEGF), was the key mediating factor of this phenomenon. Our findings suggest that hyperhomocysteinemia might cause choroidal angiogenesis.
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PMID:Hyperhomocysteinemia Causes Chorioretinal Angiogenesis with Placental Growth Factor Upregulation. 3036 76

The main goal of this work is to clarify and quantify, by means of mathematical analysis, the role of structural viscoelasticity in the biomechanical response of deformable porous media with incompressible constituents to sudden changes in external applied loads. Models of deformable porous media with incompressible constituents are often utilized to describe the behavior of biological tissues, such as cartilages, bones and engineered tissue scaffolds, where viscoelastic properties may change with age, disease or by design. Here, for the first time, we show that the fluid velocity within the medium could increase tremendously, even up to infinity, should the external applied load experience sudden changes in time and the structural viscoelasticity be too small. In particular, we consider a one-dimensional poro-visco-elastic model for which we derive explicit solutions in the cases where the external applied load is characterized by a step pulse or a trapezoidal pulse in time. By means of dimensional analysis, we identify some dimensionless parameters that can aid the design of structural properties and/or experimental conditions as to ensure that the fluid velocity within the medium remains bounded below a certain given threshold, thereby preventing potential tissue damage. The application to confined compression tests for biological tissues is discussed in detail. Interestingly, the loss of viscoelastic tissue properties has been associated with various disease conditions, such as atherosclerosis, Alzheimer's disease and glaucoma. Thus, the findings of this work may be relevant to many applications in biology and medicine.
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PMID:The role of structural viscoelasticity in deformable porous media with incompressible constituents: Applications in biomechanics. 3038 Mar 16


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