Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0314719 (dry eye)
 2,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphological and biophysical techniques described in this study have shown that membrane derangement occurs in human cataractous lenses. The data suggest that these disruptions were globules, vacuoles, multilamellar membranes and clusters of highly undulating membranes. Deleterious structural damage of the lens fibre cell plasma membranes serve as the primary light-scattering centres that cause the observed lens opacity. Nuclear cataract, a major cause of loss of lens transparency in the aging human, has been thought to be associated with oxidative damage, particularly at the site of the nuclear plasma membrane. Phospholipid molecules modified by oxygen accumulate in the lipid bilayer, change its geometry and impair lipid-lipid and protein-lipid interactions in lenticular fibre membranes. Lipid peroxidation (LPO) is a causative and pathogenic factor in cataract. Increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides, oxy-derivatives of phospholipid fatty acids) and end-fluorescent LPO products have been detected in the lipid moieties of aqueous humour samples and human lenses obtained from patients with senile and complicated cataracts as compared with normal donors. In the present study, a rapid and simple high-performance liquid chromatographic (HPLC) assay for determination of imidazole-containing dipeptides in the aqueous humour of the eye was developed. The method was applied to determine the pharmacokinetic parameters and the time-course of N-acetylcarnosine and L-carnosine-related product in the eye, following a single dosage of topical ocular administration of peptide. Utilising data from pharmacokinetic studies and the specific purity of the N-acetylcarnosine (NAC) ingredient as a source of the pharmacological principle L-carnosine, we have created an ophthalmic time-release prodrug form including the US FDA-approved carboxymethylcellulose lubricant and other essential ingredients (Can-C, private label Nu-Eyes). This formulation increases the intraocular absorption of L-carnosine in the aqueous humour and optimises its specific antioxidant activity in vivo while reducing the toxic effects of lipid peroxides on the crystalline lens. L-carnosine that enters the aqueous humour can accumulate in the lens tissue for a reasonable period of time. The presence of L-carnosine in transparent crystalline lenses during normal aging was detected and its concentration in this case was about 25 microM. At different stages of cataract development, the level of L-carnosine drastically decreased, reaching about 5 microM in ripe human cataracts. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation or subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humour at the time level over 30 minutes at a concentration exceeding that in placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. Use of NAC prodrug eye drops optimises the clinical effects of L-carnosine in the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a clinical effect with NAC ophthalmic prodrug, and show that the magnitude and duration of this effect are directly related to the bioavailability of L-carnosine released from NAC in the aqueous humour of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders that have a component of oxidative stress in their pathogenesis (including cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, and corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). There is a need for further and better collaboration between Innovative Vision Products' cataract control and ophthalmic services, improved education of people affected by cataract, a commitment that N-acetylcarnosine eye drops will be the preferred treatment before orthodox cataract surgery is attempted, and consideration of outcomes and a possible role of the NAC drug cataract treatment as source of referral for orthodox surgical, ophthalmic and optometric services.
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PMID:Analysis of lipid peroxidation and electron microscopic survey of maturation stages during human cataractogenesis: pharmacokinetic assay of Can-C N-acetylcarnosine prodrug lubricant eye drops for cataract prevention. 1627 59

Cataract is the dominant cause of blindness worldwide. Studies of the morphological structure and biophysical changes of the lens in human senile cataracts have demonstrated the disappearance of normal fiber structure in the opaque region of the lens and the disintegration of the lens fiber plasma membrane in the lens tissue. Morphological and biochemical techniques have revealed the regions in human cataractous lenses in which the plasma membrane derangement occurs as the primary light scattering centers which cause the observed lens opacity. Human cataract formation is mostly considered to be a multifactorial disease; however, oxidative stress might be one of the leading causes for both nuclear and cortical cataract. Phospholipid molecules modified with oxygen, accumulating in the lipid bilayer, change its geometry and impair lipid-lipid and protein-lipid interactions in lenticular fiber membranes. Electron microscopy data of human lenses at various stages of age-related cataract document that these disruptions were globules, vacuoles, multilamellar membranes, and clusters of highly undulating membranes. The opaque shades of cortical cataracts represent cohorts of locally affected fibres segregated from unaffected neighbouring fibres by plasma membranes. Other potential scattering centers found throughout the mature cataract nucleus included variations in staining density between adjacent cells, enlarged extracellular spaces between undulating membrane pairs, and protein-like deposits in the extracellular space. These affected parts had membranes with a fine globular aspect and in cross-section proved to be filled with medium to large globular elements. Lipid peroxidation (LPO) is a pathogenetic and causative factor of cataract. Increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides, fatty acid oxy-derivatives) and end fluorescent LPO products were detected in the lipid moieties of the aqueous humor samples and human lenses obtained from patients with senile and complicated cataracts as compared to normal donors. Utilizing the pharmacokinetic studies and the specific purity N-acetylcarnosine (NAC) ingredient as a source of pharmacological principal L-carnosine, we have created an ophthalmic time-release prodrug form combined with a muco-adhesive lubricant compound carboxymethylcellulose and other essential corneal absorption promoter excipients tailoring the increased intraocular absorption of L-carnosine in the aqueous humor and optimizing its specific effect in producing the basic antioxidant activity in vivo and reducing toxic effects of lipid peroxides to the crystalline lens. L-Carnosine that finds its way into the aqueous humor can accumulate in the lens tissue for a reasonable period of time. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation, subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. The NAC prodrug eye drops optimize the clinical effects for the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a particular NAC ophthalmic prodrug's clinical effect; the suitable magnitude and duration of this effect suggest dose-related bioavailability of L-camosine released from NAC in the aqueous humor of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders which have a component of oxidative stress in their genesis (including cataract and after-cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). The clinical efficacy of N-acetylcarnosine lubricant eye drops in ripe cataracts and retinal disorders can be enhanced in combined treatment with a patented oral formulation (Can-C Plus) of non-hydrolyzed carnosine including synergistic compounds (histidine, D-panthethine) with chaperone activity towards lens crystallins and oral supplementation with N-acetylcysteine providing an alternate means of boosting reduced glutathione (GSH) synthesis in the lens.
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PMID:Potentiation of intraocular absorption and drug metabolism of N-acetylcarnosine lubricant eye drops: drug interaction with sight threatening lipid peroxides in the treatment for age-related eye diseases. 2040 4