Evaluación piloto de la reducción de niveles séricos de productos de glicación avanzada (AGEs) sobre la electrofisiología de la visión, en pacientes con diabetes mellitus tipo 2 / Pilot evaluation of the serum levels reduction of advanced glication products (AGEs) on the vision electrophysiology in type 2 diabetic patients

BACKGROUND: Diabetic vascular complications are associated with elevated concentrations of advanced glycation end-products (AGEs). These substances can be originated endogenously by hyperglycaemia and oxidative stress, but also by dietary intake. There is indirect evidence suggesting that these complications can be prevented by lowering AGEs levels by dietary or pharmacological interventions, however its clinical benefits are still not clear enough because this would require long periods of treatment. Specific neuro-ophthalmologic tests like Multifocal Electroretinogram (MFERG) and visual evoked potentials (VEP) can detect retinal and myelinic nerve early changes, and thus could represent good methods to study the results of certain interventions in shorter lapses. The aim of this preliminary study was to evaluate the effects of a pharmacological intervention designed to lower AGEs levels, on these variables. PATIENTS AND METHODS: We included 7 patients with type 2 diabetes (DM2), with more than 5 and less than 10 years of disease, without clinically evident micro and macrovascular disease, without renal failure, hypothyroidism nor vitamin B12 deficiency, whose AGEs dietary intake was moderately elevated or high (according to dietary recalls). Upon admission, a clinical evaluation, urine and blood samples were obtained for routine labs, plus ultrasensitive C Reactive Protein (usCRP) as an inflammatory marker, and carboxymethyl-lysine (CML) as representative of AGEs. Then a complete ophthalmologic evaluation was performed, including fundus, MFERG and VEP. After the initial evaluation, placebo capsules were prescribed (12 daily capsules, 4 with each main meal) during 3 months, repeating the same initial evaluation at completion of this period. Then the active treatment followed, with capsules containing cholestyramine (4 capsules containing 500 mg each, totaling 6 g per day). Patients were cited each month, to register adverse events and repeating the same evaluation after this second 3 months period. RESULTS: The sample was composed of 2 male patients, mean age was 55.1 ± 3.8 years, and diabetes was managed with metformin plus other oral agents or o insulin (4 cases). In addition, 4 patients received lipid lowering and 4 antihypertensive drugs. Metabolic control and lipid levels were variable (ranges of HbA1c 6.2-8.4%, LDL cholesterol 45-141 mg/dL, triglycerides 70-220 mg/dL). AGEs levels represented by CML were highly variable (median 31.7, range min-max 3.4-58.9 ug/uL). Basal usCRP was also variable (median 405.9, range min-max 265.6-490.7 mg/L). The treatment was well tolerated, except for mild constipation associated with cholestiramine intake. No significant changes in electroretinography or evoked potentials were observed when comparing the initial placebo period with cholestyramine treatment. A significant increase in triglyceride levels and decrease of vitamin D levels after cholestyramine treatment was observed. No changes were detected in serum concentrations of CML, usCRP or glycemic control, after treatment. The latter variables were not correlated with neurophthalmologic studies. DISCUSSION: In this preliminary study we did not observe changes in MFERG nor VEP after 6 g/day cholestyramine treatment, which did not induce lowering of CML levels. This could be attributed to the many limitations of a pilot study, such as a small sample size, short duration of treatment, reduced doses. However this design allowed to evaluate the patients´ tolerance to the drug and rule out adverse effects, in order to plan further studies using the necessary doses to obtain lowering of AGEs

Influence of dietary lysine and arginine interrelationship on growth performance, carcass characteristics and immune response in Japanese quail

This study was designed to determine the effect of dietary supplementation of extra Lysine [LYS] and/or Arginine [ARG] than normal requirements of Japanese quail chicks and their interaction on growth performance, carcass quality, immune response and nutrient digestibility in Japanese quail. A total of 672 one - day old Japanese quail chicks were used in this study and randomly allotted into equal 16 groups [42 per each] of mixed sex. Group 1 was fed basal diet without supplementation [control]. Quail chicks of groups 2, 3 and 4 were fed on the basal diet supplemented with ARG at 110, 120 and 130% of the NRC [1994] requirement respectively. While quail chicks of groups 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16 were fed basal diet supplemented with LYS/ARG at ratios of 110/100, 110/110, 110/120, 110/130, 120/100, 120/110, 120/120, 120/130, 130/100, 130/110, 130/120 and 130/130. From the obtained data it was observed that ARC supplementation without LYS [groups 2, 3 and 4] showed non significant improvement in body weight, weight gain, RGR, FCR when compared with control and also supplementation of LYS alone [groups 5, 9 and 13] showed non significant improvement in the growth performance parameters. While, both ARG and LYS supplementation had no effect on growth rates as showed in quail chicks of groups 15 and 16. There was an improvement of immune response with LYS and/or ARG supplementation as noticed in increased phagocytic activity and HI titer in quail chicks especially in the highest level of ARG supplementation [group, 4]. Regarding serum parameters, there was an increase in serum total protein level in all groups fed on LYS and/or ARG supplemented diets when compared with the control and a significant increase in serum total cholesterol in the groups supplemented with higher levels of LYS alone [groups 5, 9 and 13]. Both LYS and ARG supplemented groups had some variation in concentration of SGPT and SGOT and the highest level was observed in higher supplement level of ARG [group 4], while serum uric acid concentration increased with the level of LYS and/or ARG supplementation. There was a significant increase lymphoid organ in quail chicks of group 4 which fed basal diet supplemented with LYS/ ARG at 100/130 when compared with the control and other supplemented groups. LYS or ARG supplementation had no effect on dressing and liver percent, while both of them improved thigh percent, reduced visible fat accumulation% and improved breast meat percent and LYS is more efficient for increasing breast meat when compared with control. LYS supplementation is more related to increase CP% in breast meat than ARG and higher supplementation of both of amino acids increase CP% in liver and generally that supplement had minor effect on the nutrient digestibility