scholarly journals Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

2020 ◽  
Vol 9 (8) ◽  
pp. 2510
Author(s):  
Katerina Pavelcova ◽  
Jana Bohata ◽  
Marketa Pavlikova ◽  
Eliska Bubenikova ◽  
Karel Pavelka ◽  
...  

Urate transporters, which are located in the kidneys, significantly affect the level of uric acid in the body. We looked at genetic variants of genes encoding the major reabsorption proteins GLUT9 (SLC2A9) and URAT1 (SLC22A12) and their association with hyperuricemia and gout. In a cohort of 250 individuals with primary hyperuricemia and gout, we used direct sequencing to examine the SLC22A12 and SLC2A9 genes. Identified variants were evaluated in relation to clinical data, biochemical parameters, metabolic syndrome criteria, and our previous analysis of the major secretory urate transporter ABCG2. We detected seven nonsynonymous variants of SLC2A9. There were no nonsynonymous variants of SLC22A12. Eleven variants of SLC2A9 and two variants of SLC22A12 were significantly more common in our cohort than in the European population (p = 0), while variants p.V282I and c.1002+78A>G had a low frequency in our cohort (p = 0). Since the association between variants and the level of uric acid was not demonstrated, the influence of variants on the development of hyperuricemia and gout should be evaluated with caution. However, consistent with the findings of other studies, our data suggest that p.V282I and c.1002+78A>G (SLC2A9) reduce the risk of gout, while p.N82N (SLC22A12) increases the risk.

Author(s):  
Pablo A. Scacchi Bernasconi ◽  
Nancy P. Cardoso ◽  
Roxana Reynoso ◽  
Pablo Scacchi ◽  
Daniel P. Cardinali

AbstractCombinations of fructose- and fat-rich diets in experimental animals can model the human metabolic syndrome (MS). In rats, the increase in blood pressure (BP) after diet manipulation is sex related and highly dependent on testosterone secretion. However, the extent of the impact of diet on rodent hypophysial-testicular axis remains undefined. In the present study, rats drinking a 10% fructose solution or fed a high-fat (35%) diet for 10 weeks had higher plasma levels of luteinizing hormone (LH) and lower plasma levels of testosterone, without significant changes in circulating follicle-stimulating hormone or the weight of most reproductive organs. Diet manipulation brought about a significant increase in body weight, systolic BP, area under the curve (AUC) of glycemia after an intraperitoneal glucose tolerance test (IPGTT), and plasma low-density lipoprotein cholesterol, cholesterol, triglycerides, and uric acid levels. The concomitant administration of melatonin (25 μg/mL of drinking water) normalized the abnormally high LH levels but did not affect the inhibited testosterone secretion found in fructose- or high-fat-fed rats. Rather, melatonin per se inhibited testosterone secretion. Melatonin significantly blunted the body weight and systolic BP increase, the increase in the AUC of glycemia after an IPGTT, and the changes in circulating lipid profile and uric acid found in both MS models. The results are compatible with a primary inhibition of testicular function in diet-induced MS in rats and with the partial effectiveness of melatonin to counteract the metabolic but not the testicular sequelae of rodent MS.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sung Kweon Cho ◽  
Beomsu Kim ◽  
Woojae Myung ◽  
Yoosoo Chang ◽  
Seungho Ryu ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Abdullah M. Alzahrani ◽  
Georgia Ragia ◽  
Hamza Hanieh ◽  
Vangelis G. Manolopoulos

Polymorphisms in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence the dose variability of coumarinic oral anticoagulants (COAs). Substantial inter- and intraethnic variability exists in the frequencies ofCYP2C9∗2 and∗3 andVKORC1–1639A alleles. However, the prevalence ofCYP2C9andVKORC1genetic variants is less characterized in Arab populations. A total of 131 healthy adult subjects from the Al-Ahsa region of Saudi Arabia were genotyped for theCYP2C9∗2 and∗3 andVKORC1–1639G>A polymorphisms by PCR-RFLP method. The frequencies of theCYP2C9∗2 and∗3 andVKORC1–1639A alleles were 13.3%, 2.3%, and 42.4%, respectively, with no subjects carrying 2 defective alleles. The frequencies of theCYP2C9∗3 andVKORC1–1639A alleles were significantly lower than those reported in different Arabian populations. None of the subjects with theVKORC1–1639AA genotype were carriers ofCYP2C9∗1/∗3 genotypes that lead to sensitivity to COAs therapy. The low frequency of theCYP2C9∗3 allele combined with the absence of subjects carrying 2 defectiveCYP2C9alleles suggests that, in this specific population, pharmacogenetic COAs dosing may mostly rely uponVKORC1genotyping.


2015 ◽  
Vol 61 (2) ◽  
pp. 12-20
Author(s):  
D A Gusakova ◽  
S Yu Kalinchenko ◽  
A A Kamalov ◽  
Yu A Tishova

Abdominal obesity is a major component of metabolic syndrome (MS) considered to be the key factor contributing to the development of testosterone deficiency (hypogonadism) in men. Bearing in mind the etiopathogenetic relationship between MS and urolithiasis (UL), the present study was undertaken for the purpose of elucidating the role of the main biochemical risk factors of metabolic syndrome in men, evaluating the influence of correction of hypogonadism on these factors, and optimization of the treatment and prevention of MS in these patients. The study included 90 men presenting with hypogonadism in whom the serum levels and renal excretion of the main lithogenic substances (uric acid, calcium, phosphates, magnesium) and urine pH were measured. At the first stage of the study, the patients were allocated to two groups. Group 1 was comprised of 52 patients with UL, group 2 consisted of 38 patients without UL. The patients of group 1 were found to suffer hyperuricemia (the serum uric acid levels 430 mcmol/l and higher). The patients of both groups exhibited hyperuricosuria (daily uric acid excretion over 4.13 mmol/24 hr) with the urine pH value of 5.5 and lower. The serum uric acid concentration was shown to positively correlate with the insulin and C-peptide levels. At the second stage of the study, 65 randomly selected patients were divided into two groups in one of which (n=40) they were given testosterone therapy. Compensation of hypogonadism in these patients was associated with a significant reduction of the serum uric acid levels and its daily excretion, an increase and normalization of urine pH, and a rise in the serum magnesium concentration, Similar significant changes of the same parameters were absent in the control subjects (n=25). Moreover, testosterone therapy improved characteristics of lipid and carbohydrate metabolism, caused reduction in the body weight, BMI, and the severity of insulin resistance.


2021 ◽  
Author(s):  
Shaukat Ali ◽  
Maria Akram Minhas ◽  
Uzma Azeem Awan ◽  
Shumaila Mumtaz ◽  
Hafiz Abdullah Shakir ◽  
...  

Abstract Among heavy metals, lead is one of the very toxic pollutants of the environment. Its accumulating nature in the body makes it a great threat to public health particularly when humans consume lead intoxicated foods like chickens. The main purpose of the conducted research was to elucidate the bioaccumulation of lead in different organs of chickens and its toxicological effects on various organs and biochemical parameters. An experimental study on the effect of lead acetate toxicity in chicks was conducted by orally administration for consecutive thirty days. Thirty-chicks were categorized into A, B, C, D, E, and F groups with lead acetate dose rate 0, 71, 142, 213, and 284 mg/kg body weight, correspondingly. During the experiment, various biochemical parameters (uric acid, GPT, creatinine, ALP, LDH, ASAT, ALT, glutathione, superoxide dismutase) were measured employing commercially available kits. At the end of experimentation, and lead accumulation in liver, kidney and brain was estimated by absorption spectrophotometer. Some biochemical parameters like uric acid, GPT, creatinine, ALP, LDH, AST, and ALT were increased while the level of glutathione and superoxide dismutase, was found to be decreased after exposure to lead acetate. In present study, the pattern of metal accumulation in different organs directly related with concentration of metal. The order of metal accumulation in organs is; liver > kidney > brain. In the present study, supplementation of lead acetate has affected the exposed chicken. Mostly the blood profile and chemistry are perturbed. These effects might be due to the accumulation of lead in the brain, kidneys, and liver which may result in neurotoxicity, nephrotoxicity, and hepatotoxicity. To refine such outcomes, further studies in the future are recommended.


Author(s):  
Vasyl Muraveinyk ◽  
Dmytro Maltsev ◽  
Anton Muraveinyk ◽  
Oleksandr Tarasevych

Backgrounds. Development and testing of new methods of detoxification and anti-inflammatory therapy are important tasks of modern medicine in view of the continuous spread of diseases accompanied by persistent inflammatory reaction and/or accumulation in the body of toxic compounds, and the lack of effectiveness of currently used anti-inflammatory and anti-inflammatory treatments. Aim of the study: to study the clinical efficacy and safety by the dynamics of disease symptoms and some laboratory biochemical parameters of original highly mineralized products for external use in inflammatory human diseases. Materials and methods. An uncontrolled pilot study was conducted to investigate the efficacy and safety of highly mineralized products according to the most promising indications to determine appropriate directions for further controlled clinical trials. We recruited 3 patient groups of 10 people each. The first group received compressed wipes highly mineralized in the form of applications to the skin around arthritic joints. In the second group, compression bandages highly mineralized in the form of extensive and prolonged cutaneous applications in the trunk and extremities for detoxification in patients with chronic renal failure were used. The third group received a universal spray highly mineralized to eliminate the manifestations of skin itching in the form of aerosol spraying. Control was performed on the subjective feelings of patients using a visual analogue scale of pain and itching, clinical examination data and the dynamics of some laboratory biochemical parameters such as serum concentration of creatinine, urea, uric acid. Statistical analysis of the results was performed by structural and comparative analysis methods. Results and discussion. Complete remission of arthritis symptoms after a 10-day course of therapy was achieved in 50% of cases, and other patients showed significant improvement. On a visual analog scale, all patients experienced a decrease in pain intensity of at least 50% during the first 3-4 local napkin compression applications. Results of pilot tests of highly mineralized compression bandages in patients with chronic renal failure indicate some improvement in well-being and a slight decrease in serum concentrations of creatinine and uric acid by 10-30% in the subgroup of patients with initial serum kreatinine concentration to 200 µmol/l. The highly mineralized universal spray provides rapid (within a few seconds to 2 minutes) and complete or almost complete elimination of itching sensations at the site of application for 1 to 12 hours in all patients, regardless of the origin of the itching, but depending on its intensity. Conclusions. Original highly mineralized products are potentially effective and safe to use in the specified pathology according to the approved application protocols. There is a need for further controlled research in the outlined areas.


Author(s):  
Tamilarasi G P ◽  
Sabarees G

Oxidation is an essential reaction in the human body, which determines the expression of proteins in the body. This results in the altered expression like rapid growth resulting in cancers and other disorders. Many synthetic drugs are available in the market that is effective in limiting the free radical generation and the reaction of radicals with cells. Unfortunately, all those synthetic drugs were found to cause side effects and adverse effects in the body. But given the accuracy of the predictability of the results and administration, this research focuses on testing the anti-oxidant efficiency in rat models testing the biochemical parameters. Investigations have also been done on the anti-oxidant activity of Tectona, but every research was concentrated to prove the anti-oxidant activity only. extract had been tested for anti-oxidant activity by estimating various tissue parameters and it showed better activity. As predicted, there is a significant difference in the and results which can be explained are due to the physiological conditions that exist inside the body.


Author(s):  
Khvorova L.S. ◽  
Byzov V.A.

The article is devoted to the creation of a carbohydrate product with rosehip extract in the form of sweets (glucose Fudge) with a therapeutic and preventive effect aimed at restoring the body of people exposed to intense physical and mental stress and the effects of damaging environmental factors. As carbohydrates in the recipe, simple carbohydrates (glucose) and complex carbohydrates in the form of starch molasses containing (maltose, tri - Tetra - sugars, dextrins) are used. Glucose in the formulation is the main energy ingredient, sweetener and structure-forming component that gives the product a solid consistency due to crystallization. The medicinal effect of the product is provided by rosehip extract. Numerous published studies have established its vitamin, immunostimulating and antioxidant activity, inhibition of uric acid formation and obesity, which are associated with flavonoids, other phenolic compounds, and vitamins. The list of medicinal properties of rosehip extract shows the feasibility of using it in additional nutrition of people in order to prevent diseases. For the formulation of our sweets, the extraction of crushed rosehip fruits was carried out three times with hot water at a temperature of 65-700C, followed by concentration of the extract under vacuum to 25-30% SV. The resulting extract-concentrate was introduced into the formulation in a dosage of 5.5% SV per 100 g of SV glucose Fudge, which provided the necessary dosage for the product when used from 3 (for children) to 10 sweets a day (for adults) for the prevention of colds.


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