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Carnosine, CoQ10, Bifidobacteria, and Olive oil

January 2018

Carnosine

Advanced glycation end products and diabetic complications.

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.

Korean J Physiol Pharmacol. 2014 Feb;18(1):1-14.

The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study.

OBJECTIVE: To determine the efficacy of a topical antioxidant formulation including N-acetyl carnosine in the treatment of canine cataract in a preliminary nonplacebo, controlled, unmasked study. ANIMALS STUDIED: Thirty dogs of varying breeds and ages with a spectrum of lens opacities ranging from nuclear sclerosis to total mature cataract. METHODS: Dogs were treated three times daily with topical 2% N-acetyl carnosine in a buffered vehicle containing the antioxidants glutathione, cysteine ascorbate, L-taurine and riboflavin (Ocluvet, Practivet, Phoenix, AZ, USA). Dogs were examined prior to treatment and at 2, 4 and 8 weeks during treatment, by direct and indirect ophthalmoscopy and slit-lamp biomicroscopy after pharmacologic pupil dilation. Photographic documentation of lens opacity was achieved by retroillumination photography, with three photographs taken at each examination time-point. A lens opacification index (LOI), determined by integration of the grayscale level of each pixel across the image, was evaluated by computerized image analysis of digitized images. Alteration in mean LOI was determined for each animal, having normalized the initial LOI. RESULTS: Fifty-eight eyes of 30 dogs were evaluated, 22 with mature cataract, 13 with immature cataract, 9 with cataract associated with other intraocular disease such as uveitis and 14 with nuclear sclerosis alone. One dog was unilaterally anophthalmic after previous enucleation and one had a phthytic eye after previous uveitis-induced glaucoma. Image analysis showed a reduction in mean LOI in all cataract groups (mean resolution in opacity of 2.3 +/- 0.33% for all cataracts), although this was only statistically significant in those eyes with immature cataract (mean resolution of opacity 4.5 +/- 0.33%) or nuclear sclerosis (mean decrease in opacity 5 +/- 0.37%). Reduction in lens opacity was seen in eyes with mature cataract (0.5 +/- 0.4%) and in miscellaneous cataract associated with intraocular inflammation (1.3 +/- 0.4%), but these changes were not statistically significant. Owner evaluation of visual capability, however, suggested improvement in vision in 80% of cases by the end of the study. CONCLUSIONS: This study demonstrates some marginal reduction in lens opacification in a substantial number of cases of canine cataract with the use of a topical nutritional antioxidant formulation including N-acetyl carnosine. Lens opacification was improved with treatment in eyes with immature cataract or nuclear sclerosis while in eyes with mature cataract or cataract with associated intraocular inflammatory pathology less reduction was seen.

Vet Ophthalmol. 2006 Sep-Oct;9(5):311-6.

Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats.

PURPOSE: To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. METHODS: Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol/l plasma glucose) and diabetic rats (>14 mmol/l plasma glucose). Animals in the treated groups received CA, AG, and ASA as drops to the left eyes starting from the day of streptozotocin injection. Progression of lens opacification was recorded using the slit lamp at regular time intervals. All the rats were killed after the week 13, and the levels of advanced glycation end products (AGE), glutathione reductase (GR), catalase (CAT), and glutathione (GSH) were determined. RESULTS: Lens opacification progressed in a biphasic manner in the diabetic rats, an initial slow increase during the first eight weeks of diabetes followed by a steep increase in the next five weeks. Carnosine treatment delayed the progression of cataracts in diabetic rats, and the delay was statistically significant on the fourth week of diabetes (p<0.05, when compared with untreated moderately diabetic rats). A decrease in the antioxidant enzymes of CAT and the level of GSH was found in the lens of the untreated diabetic rats at 13 weeks after injection. Some protection was provided in the treated eyes. The level of glycation in the untreated diabetic rats was significantly higher than that in the normal rats (p<0.001). After treatment with CA, AG, and ASA, those diabetic rats had a lower level of glycated lens protein compared to the untreated diabetic rats (p<0.001). CONCLUSIONS: These results thus suggest that the effect of CA, AG, and ASA is indeed inhibition of the formation of AGEs. However, the effect of CA, AG, and ASA is overwhelmed by the excessive accumulation of AGEs in the severely diabetic rats. CA compared with AG and ASA treatment can delay the progression of lens opacification in the diabetic rats only during the earlier stages. It also protects against the inactivation of enzymes.

Mol Vis. 2008;14:2282-91. Epub 2008 Dec 11.

The hallmarks of aging.

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.

Cell. 2013 Jun 6;153(6):1194-217.

Role of fructose concentration on cataractogenesis in senile diabetic and non-diabetic patients.

BACKGROUND: Fructose intake has increased steadily during the past 2 decades. Fructose, like other reducing sugar, can react with proteins, which may account for aging and cataract formation. Fructose participates in glycation (fructation) and advanced glycation endproducts (AGE) formation some ten times faster than glucose. This study aims to determine the fructose concentration and correlate with antioxidant status in senile diabetic and non-diabetic cataract patients. METHODS: The study included 124 subjects. Of them, 31 were normal senile subjects, 33 were senile diabetic patients without cataract, 30 were senile diabetic patients with cataract, and 30 were senile non-diabetic patients with cataract. The patients were selected on clinical grounds from Eye Ward, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. RESULTS: Serum fructose was significantly increased (P < 0.001) in senile diabetic patients with and without cataract and senile non-diabetic patients with cataract as compared with senile control subjects. Negative significant correlation was observed between serum fructose and serum total antioxidant status in diabetic and non-diabetic patients with cataract. Positive significant correlation was observed between serum fructose and s-AGEs in diabetic and non-diabetic patients with cataract. Serum total antioxidant status was found to be significantly decreased (P < 0.001) in senile diabetic patients with and without cataract and senile non-diabetic patients with cataract as compared with senile control subjects. Fasting blood glucose, HbA(1C) and serum fructosamine were significantly increased (P < 0.001) in senile diabetic patients with or without cataract as compared with senile non-diabetic patients with cataract and senile control subjects. CONCLUSIONS: The results indicate that the increased fructose concentration which induces oxidative stress in diabetic and non-diabetic patients with cataract may be a predictor for cataractogenesis.

Graefes Arch Clin Exp Ophthalmol. 2009 Jun;247(6):809-14.

Advanced glycation end products in senile diabetic and nondiabetic patients with cataract.

BACKGROUND: Advanced glycation end products (AGE) have been reported to contribute to aging and cataract formation in the lens. In the present study, AGE immunoreactivity in human serum samples of normal senile subjects (n=31), senile diabetic patients without cataract (n=33), senile diabetic patients with cataract (n=30), senile nondiabetic with cataract (n=30), and normal young subjects (n=31) was investigated. METHODS: A noncompetitive ELISA with polyclonal anti-AGE antibody was performed. The patients were selected on clinical grounds from Eye Ward, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. RESULTS: Fasting blood glucose, glycosylated hemoglobin, and serum fructosamine were estimated. Fasting blood glucose, HbA(1C), and serum fructosamine levels were significantly (P<.001) increased in senile diabetic patients with and without cataract as compared to nondiabetic senile patients with cataract and senile control subjects. However, the serum AGEs were found to be significantly (P<.001) increased in senile diabetic patients with cataract and senile nondiabetic patients with cataract followed by the diabetic patients without cataract as compared to senile control and young control subjects. In contrast to all four senile groups, the serum AGEs were significantly (P<.001) lower in young control subjects. CONCLUSIONS: The AGE distribution in the senile groups corroborates the hypothesis that the advanced glycation process might have a role in cataract formation, which in diabetic patients occurs vigorously as compared with nondiabetic cataract patients.

J Diabetes Complications. 2009 Sep-Oct;23(5):343-8.

Advanced glycation end products in diabetic and non-diabetic human subjects suffering from cataract.

Advanced glycation end products (AGEs) play a pivotal role in loss of lens transparency, i.e., cataract. AGEs formation occurs as a result of sequential glycation and oxidation reaction between reducing sugars and protein. AGEs production takes place throughout the normal aging process but its accumulation is found to be more rapid in diabetic patients. In this study, we quantified AGEs and N-(carboxyethyl) lysine (CEL) in human cataractous lenses from non-diabetic (n=50) and diabetic patients (n=50) using ELISA. We observed significantly higher (p<0.001) levels of lens AGEs and CEL in diabetic patients with cataract as compared with their respective controls. The presence of AGEs and CEL was also determined by western blotting and immuno-histochemical analysis. Furthermore, isolated b-crystallin from cataractous lenses of non-diabetic and diabetic patients was incubated with different sugars to evaluate the extent of glycation in a time dependent manner. Our data indicated more pronounced glycation in patients suffering from diabetes as compared to non-diabetics subjects demonstrating the need to focus on developing normoglycemic approaches. Such studies may provide an insight in developing therapeutic strategies and may have clinical implications.

Age (Dordr). 2011 Sep;33(3):377-84.

Glycation of cataractous lens in non-diabetic senile subjects and in diabetic patients.

Early- and advanced-stage products in the Maillard reaction, glycation, were measured in patients with diabetic or senile cataracts. Early-stage products were measured by means of furosine, which is an acid-hydrolysis product derived from fructose-lysine. Advanced-stage products were measured by fluorometry using high-performance liquid chromatography. Furosine levels were high (listed in descending order) in capsule, cortex and nucleus in both diabetic and senile cataracts. The advanced-stage products were also high (listed in descending order) in nucleus, cortex and capsule in both diabetic and senile cataracts. These results suggest that advanced-stage products might accumulate in larger amounts in the nucleus and cortex than in the capsule, resulting in the formation of cataracts. The study also revealed that the Maillard reaction plays an important role in causing not only diabetic cataracts but also senile cataracts.

Exp Eye Res. 1988 Mar;46(3):415-20.

Role of glycation in human lens protein structure change.

PURPOSE: Protein glycation may be involved in cataract development, by altering protein structure, particularly amino acid composition, and formation of fluorophores through a Maillard reaction. This study was designed to evaluate major changes in early and advanced (fluorescent) glycation products, with special emphasis on glycation-induced changes in amino acid composition of lens proteins. METHODS: We analyzed 50 human cataractous lenses (25 diabetic and 25 non-diabetic). Glycated proteins were isolated by affinity chromatography. Glycated and non-glycated proteins were separated by molecular sieve chromatography and further analyzed by RP-HPLC to establish the amino acid content. Early glycation levels were determined as furosine content and advanced glycation products were quantified by the characteristic fluorescence. RESULTS: Specific lens fractions (HMW and LMW) present significant differences in fluorescence levels between glycated and non-glycated proteins, specially in cataractous lenses from diabetic patients in which all proteins analyzed presented higher glycation levels than in non-diabetic patients. The amino and analysis of glycated proteins also revealed some important differences in specific basic residues (namely Lys, Arg and His) compared to the non-glycated fraction. CONCLUSIONS: The results suggest that protein glycation may be involved in changes in amino acid composition and fluorophore formation. This process may well account for the increased risk factor that diabetes represents for cataract development.

Eur J Ophthalmol. 1996 Apr-Jun;6(2):155-61.

Exercise interventions in polypathological aging patients that coexist with diabetes mellitus: improving functional status and quality of life.

In elderly populations, diabetes is associated with reduced muscle strength, poor muscle quality, and accelerated loss of muscle mass. In addition, diabetes mellitus increases risk for accelerated aging and for the development of frailty syndrome. This disease is also associated with a polypathological condition, and its complications progressively affect quality of life and survival. Exercise interventions, including resistance training, represent the cornerstones of diabetes management, especially in patients at severe functional decline. This review manuscript aimed to describe the beneficial effects of different exercise interventions on the functional capacity of elderly diabetics, including those at polypathological condition. The SciELO, Science Citation Index, MEDLINE, Scopus, SPORTDiscus, and ScienceDirect databases were searched from 1980 to 2015 for articles published from original scientific investigations. In addition to the beneficial effects of exercise interventions on glycemic control, and on the cardiovascular risk factors associated with diabetes, physical exercise is an effective intervention to improve muscle strength, power output, and aerobic power and functional capacity in elderly diabetic patients. Thus, a combination of resistance and endurance training is the most effective exercise intervention to promote overall physical fitness in these patients. In addition, in diabetic patients with frailty and severe functional decline, a multicomponent exercise program including strength and power training, balance exercises, and gait retraining may be an effective intervention to reduce falls and improve functional capacity and quality of life in these patients.

Age (Dordr). 2015 Jun;37(3):64.

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