Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past decade, numerous molecular mediators of neurodegenerative diseases and neurological disorders have been identified and validated, yet few novel therapies have emerged and the unmet medical needs remain high. These molecular mediators belong to target classes such as ion channels, neurotransmitters and neurotransmitter receptors, cytokines, growth factors, enzymes and other proteins. In some cases, substantial pre-clinical validation exists, but the molecular target has not been readily druggable with small molecules, proteins or antibodies. RNA interference represents a therapeutic approach applicable to such non-druggable targets. Both non-viral and viral delivery strategies are being undertaken for in vivo silencing of molecular targets by RNA interference, which has resulted in robust efficacy in animal models of Alzheimer's disease, ALS, Huntington's disease, spinocerebellar ataxia, anxiety, depression, neuropathic pain, encephalitis and glioblastoma. These proof-of-concept data in animal models, together with the commencement of clinical trials using RNA interference for macular degeneration and respiratory syncytial virus infection, point to the potential of direct RNA interference for neurological disorders and neurodegenerative diseases.
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PMID:Therapeutic potential of RNA interference for neurological disorders. 1681 77

Late-life depression is very common and is associated with high rates of morbidity and mortality. While the field of geriatric psychiatry is focused on depression treatment, prevention is an enticing option. Prevention of late-life depression would decrease both emotional suffering and depression-associated morbidity and mortality and may decrease dependence on non-mental health professionals to detect depression and to initiate a treatment referral. This paper will review current thinking on prevention research with a particular focus on its application to late-life depression. To illustrate these issues, we discuss recent and ongoing clinical trials of interventions to prevent depression in two populations of older persons: those with age-related macular degeneration (AMD) and those with cerebrovascular disease.
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PMID:Depression in late-life: shifting the paradigm from treatment to prevention. 1685 47

Carbonic anhydrase inhibitors (CAIs) such as acetazolamide, methazolamide, ethoxzolamide and dichlorophenamide were and still are widely used systemic antiglaucoma drugs. Their mechanism of action consists in inhibition of CA isozymes present in ciliary processes of the eye (such as CA II, IV and XII), with the consequent reduction of bicarbonate and aqueous humour secretion, and of elevated intraocular pressure (IOP) characteristic of this disease. Since CA II/IV/XII are present in many other tissues/organs, generally, systemic CAIs possess undesired side effects such as numbness and tingling of extremities; metallic taste; depression; fatigue; malaise; weight loss; decreased libido; gastrointestinal irritation; metabolic acidosis; renal calculi and transient myopia. In order to avoid these undesired side effects, recently, topically effective CAIs have been developed. Two drugs are available clinically: dorzolamide and brinzolamide. Both these drugs are applied topically as water solutions/suspensions, alone or in combination with other agents (such as beta-blockers, prostaglandin derivatives, etc) and produce a consistent and prolonged reduction of IOP. Furthermore, recent reports show both the systemically as well as topically acting sulfonamide CAIs to be effective in the treatment of macular oedema and other macular degeneration diseases, for which pharmacological treatment was unavailable up to now. Much research is in act in the search of even more effective topically acting CAIs, free of the inconveniences and side effects of the presently available drugs. For achieving this goal, a recently reported strategy, the tail approach, was extensively applied for the synthesis of large numbers of derivatives possessing various physico-chemical properties. Many such new sulfonamides showed promising antiglaucoma activity in animal models of the disease.
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PMID:The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents. 1750 29

Inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms present in the eyes (CA I, II, IV and XII), with sulfonamides such as acetazolamide, methazolamide, ethoxzolamide and dichlorophenamide, is still widely used for the systemic treatment of glaucoma. The mechanism of action of these drugs consists in inhibition of CA isozymes present in ciliary processes of the eye, with the consequent reduction of bicarbonate and aqueous humour secretion, and of elevated intraocular pressure (IOP) characteristic of this disease. As isoforms CA II/IV/XII are present in many other tissues/organs, generally, systemic CAIs possess undesired side effects such as numbness and tingling of extremities; metallic taste; depression; fatigue; malaise; weight loss; decreased libido; gastrointestinal irritation; metabolic acidosis; renal calculi and transient myopia. For avoiding these side effects, recently, topically effective CAIs have been developed in the last 10 years, with two drugs available clinically: dorzolamide and brinzolamide. Both these drugs are applied topically as water solutions/suspensions, alone or in combination with other agents (beta-blockers, prostaglandin derivatives, etc) and produce a consistent and prolonged reduction of IOP. Furthermore, recent reports show both the systemically as well as topically acting sulfonamide CAIs to be effective in the treatment of macular edema, macular degeneration disease, or diabetic retinopathy, for which pharmacological treatment is unavailable up to now. Much research is in act in the search of more effective topically acting CAIs, free of the inconveniences and side effects of the presently available drugs. For achieving this goal, two recently reported strategy, the tail approach and its variant, the sugar-tail approach, were extensively applied for the synthesis of large numbers of derivatives possessing desired physico-chemical properties. Many such new sulfonamides showed promising antiglaucoma activity in animal models of the disease.
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PMID:The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. 1833 10

Family physicians have an essential role in assessing, identifying, treating, and preventing or delaying vision loss in the aging population. Approximately one in 28 U.S. adults older than 40 years is visually impaired. Vision loss is associated with depression, social isolation, falls, and medication errors, and it can cause disturbing hallucinations. Adults older than 65 years should be screened for vision problems every one to two years, with attention to specific disorders, such as diabetic retinopathy, refractive error, cataracts, glaucoma, and age-related macular degeneration. Vision-related adverse effects of commonly used medications, such as amiodarone or phosphodiesterase inhibitors, should be considered when evaluating vision problems. Prompt recognition and management of sudden vision loss can be vision saving, as can treatment of diabetic retinopathy, refractive error, cataracts, glaucoma, and age-related macular degeneration. Aggressive medical management of diabetes, hypertension, and hyperlipidemia; encouraging smoking cessation; reducing ultraviolet light exposure; and appropriate response to medication adverse effects can preserve and protect vision in many older persons. Antioxidant and mineral supplements do not prevent age-related macular degeneration, but may play a role in slowing progression in those with advanced disease.
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PMID:Vision loss in older persons. 1951 94

The use of nutritional supplements (NS) with the intention of improving health and delaying age-related chronic disease is a common practice among older adults; however, randomized controlled trials have yielded mixed results regarding the likelihood that these NS provide true health benefits. We reviewed the findings of these studies regarding the effects of NS of folic acid, vitamin B(12), vitamin B(6), and omega-3 fatty acids on health outcomes in older adults. Our conclusions include the following: Supplements of the B vitamins folate, B(12) and B(6) have been studied with regards to primary and secondary prevention of a number of major age-related chronic diseases, including cardiovascular disease (CVD), stroke, cognitive decline, and cancer. While there are some encouraging findings with regards to stroke, depression, and macular degeneration (although in only one study in the latter case), there is little evidence of benefit of B vitamin NS for delaying CVD or age-related cognitive changes. In the few cancer-related studies, the evidence of benefit is coupled with concerns about enhancing the growth of existing undiagnosed cancers. In contrast, clear health benefits have been shown with modest increases in consumption of fatty fish or fish oil supplements, including a reduction in the risk of sudden cardiac death. In addition, there is evidence that high dose fish oil supplements may lower serum triglyceride levels.
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PMID:Nutritional supplements for older adults: review and recommendations--Part II. 2039 Oct 42

During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date. The efficacy of melatonin has been assessed as a treatment of ocular diseases, blood diseases, gastrointestinal tract diseases, cardiovascular diseases, diabetes, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, infectious diseases, neurological diseases, sleep disturbances, aging and depression. Melatonin has been also used as a complementary treatment in anaesthesia, hemodialysis, in vitro fertilization and neonatal care. The conclusion of the current review is that the use of melatonin as an adjuvant therapy seems to be well funded for macular degeneration, glaucoma, protection of the gastric mucosa, irritable bowel syndrome, arterial hypertension, diabetes, side effects of chemotherapy and radiation in cancer patients or hemodialysis in patients with renal insufficiency and, especially, for sleep disorders of circadian etiology (jet lag, delayed sleep phase syndrome, sleep deterioration associated with aging, etc.) as well as in those related with neurological degenerative diseases (Alzheimer, etc.,) or Smith-Magenis syndrome. The utility of melatonin in anesthetic procedures has been also confirmed. More clinical studies are required to clarify whether, as the preliminary data suggest, melatonin is useful for treatment of fibromyalgia, chronic fatigue syndrome, infectious diseases, neoplasias or neonatal care. Preliminary data regarding the utility of melatonin in the treatment of ulcerative colitis, Crohn's disease, rheumatoid arthritis are either ambiguous or negative. Although in a few cases melatonin seems to aggravate some conditions, the vast majority of studies document the very low toxicity of melatonin over a wide range of doses.
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PMID:Clinical uses of melatonin: evaluation of human trials. 2042 9

Visual impairment and blindness impose substantial morbidity and premature mortality on the population. The direct costs for vision disorders have been shown to be more than the cost of coronary heart disease, stroke, arthritis or depression and were estimated to be $9.85 billion in 2004 in Australia. Hence it is important to identify the causes of common eye diseases and understand their aetiology which in turn would allow determination of better management strategies and treatment options. Age related Macular Degeneration, Cataract, Diabetic Retinopathy, Glaucoma and uncorrected refractive errors represent the majority of the visual impairment and blindness in Australia and various parts of the world. This article reviews the gene patents available for these eye conditions and highlights the important discoveries that have so far contributed to our understanding of these diseases and provides valuable information as to where research will be heading in the future.
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PMID:Gene patents related to common diseases of the eye. 2186 78

To investigate the relationship between depression and quantitative measures of visual function, we recruited 18 subjects with central scotomas from macular degeneration who were enrolled in a reading rehabilitation program. Psychological batteries and reading assessments were administered prior to rehabilitation; reading assessments and a measure of adaptation to vision loss were administered following rehabilitation. We investigated relationships between reported levels of depressive symptoms and reading and adaptation outcome measures by using Pearson product moment correlation analysis. Results revealed a significant relationship between depression levels and reading acuity difference scores (r(16) = 0.54, p = 0.02) and changes in adaptation to vision loss levels (r(16) = 0.62, p = 0.01), suggesting that those who reported greater depressive symptoms did not respond as well functionally to reading rehabilitation but reported greater improvement in levels of adaptation to vision loss following rehabilitation. Future research should focus on defining standard methods to assess and remediate depression as part of the rehabilitation process.
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PMID:Effect of depression on actual and perceived effects of reading rehabilitation for people with central vision loss. 2223 14

Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide.
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PMID:Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina. 2230 70


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