Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-crystallin, the major eye lens protein, is a molecular chaperone that plays a crucial role in the suppression of protein aggregation and thus in the long-term maintenance of lens transparency. Zinc is a micronutrient of the eye, but its molecular interaction with alpha-crystallin has not been studied in detail. In this paper, we present results of in vitro experiments that show bivalent zinc specifically interacts with alpha-crystallin with a dissociation constant in the submillimolar range (Kd approximately 0.2-0.4 mM). We compared the effect of Zn2+ with those of Ca2+, Cu2+, Mg2+, Cd2+, Pb2+, Ni2+, Fe2+, and Co2+ at 1 mM on the structure and chaperoning ability of alpha-crystallin. An insulin aggregation assay showed that among the bivalent metal ions, only 1 mM Zn2+ improved the chaperone function of alpha-crystallin by 30% compared to that in the absence of bivalent metal ions. Addition of 1 mM Zn2+ increased the yield of alpha-crystallin-assisted refolding of urea-treated LDH to its native state from 33 to 38%, but other bivalent ions had little effect. The surface hydrophobicity of alpha-crystallin was increased by 50% due to the binding of Zn2+. In the presence of 1 mM Zn2+, the stability of alpha-crystallin was enhanced by 36 kJ/mol, and it became more resistant to tryptic cleavage. The implications of enhanced stability and molecular chaperone activity of alpha-crystallin in the presence of Zn2+ are discussed in terms of its role in the long-term maintenance of lens transparency and cataract formation.
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PMID:Zn2+ enhances the molecular chaperone function and stability of alpha-crystallin. 1809 58

During the past 15 years, our aging colony of rhesus monkeys, consisting of animals from 20 to 37 years of age, had an annual average population of 88.2 live monkeys and, of this population, an annual average of 13.9 monkeys died spontaneously or were terminated due to severe illness. From 1980 to 1994, a total of 175 autopsies of rhesus macaques, from 20 to 37 years of age, were performed. By cumulative autopsy data, the incidence of age-related pathology in various organs was surveyed. Major geriatric diseases such as coronary sclerosis, emphysema, degenerative joint disorders, cancer, and cerebral amyloid plaque began to develop in 10 to 40% of macaques after 20 years and the incidence significantly increased after 26 years of age. Approximately 12% of aged macaques from 20 to 30 years of age died annually due to such geriatric diseases with severe complications. The average survival rate indicated that half the population at 20 years of age died by 25 years and 73% died by 30 years of age. Less than 10% of macaques survived over 30 years. Using these aged macaques as well as other juvenile to adult monkeys in our Center, clinical opththalmological and reproductive endocrinological studies, and magnetic resonance imaging (MRI) of the brain were conducted to define bioaging markers of captive rhesus monkeys. Cataracts began to develop in 20% of rhesus monkeys at 20 to 22 years of age and the rate significantly increased after 26 years of age. Menopause occurred at 26 to 27 years of age. Multiple cerebral infarctions and iron deposits in the globus pallidus and substantia nigra were detected by MRI in the aged brains. These geriatric disorders in captive aged macaques appear to be natural aging outcomes, since the simple lifestyle of these captive animals offers minimal exposure to environmental factors. Our data will offer useful paradigms for preventive or experimental studies on age-related diseases.
Age (Omaha) 1997 Jan
PMID:Age-related pathology and biosenescent markers in captive rhesus macaques. 2360 87

Eltrombopag is currently the only US Food and Drug Administration-approved thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia (ITP) in children. This oral, once-per-day therapy has shown favorable efficacy and adverse effect profiles in children. Two multicenter, double-blind, placebo controlled clinical trials (PETIT [Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)] and PETIT2 [Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body]) demonstrated efficacy in raising platelet counts, reducing bleeding, and reducing the need for concomitant ITP therapies with relatively few adverse effects. The most commonly reported drug-related adverse effects include headache, nausea, and hepatobiliary laboratory abnormalities. Long-term safety data in children are limited, and studies in adults have not revealed a clinically significant increased incidence of thrombosis, marrow fibrosis, or cataract formation. Eltrombopag has also been approved for treating refractory severe aplastic anemia (AA) and has potential for expanded use in ITP and severe AA as well as in other conditions associated with thrombocytopenia.
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PMID:Eltrombopag for use in children with immune thrombocytopenia. 2948 60