Disorder Of Purine Metabolism Research Articles

Exploring the Therapeutic Composition and Mechanism of Jiang-Suan-Chu-Bi Recipe on Gouty Arthritis Using an Integrated Approach Based on Chemical Profile, Network Pharmacology and Experimental Support Using Molecular Cell Biology.

BackgroundGouty arthritis is a common metabolic disease caused by long-term purine metabolic disorder and elevated serum uric acid. Jiang-Suan-Chu-Bi recipe (JSCBR), a traditional Chinese herbal formula prescribed according to utilization frequency and cluster analysis, has been clinically validated remedy for gouty arthritis. However, its therapeutic composition and mechanism remains unclear.MethodsIn the present study, a simple, rapid, and sensitive ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)-based chemical profiling was firstly established for comprehensively identifying the major constituents in JSCBR. A phytochemistry-based network pharmacology analysis was further performed to explore the potential therapeutic targets and pathways involved in JSCBR bioactivity. Finally, THP-1 cell model was used to verify the prediction results of network pharmacology by western blot analysis.ResultsA total of 139 compounds containing phenolic acids, flavonoids, triterpenoid saponins, alkaloids, amino acids, fatty acids, anthraquinones, terpenes, coumarins, and other miscellaneous compounds were identified, respectively. 175 disease genes, 51 potential target nodes, 80 compounds, and 11 related pathways based on network pharmacology analysis were achieved. Among these pathways and genes, NOD-like receptor signaling pathway may play an important role in the curative effect of JSCBR on gouty arthritis by regulation of NRLP3/ASC/CASP1/IL1B. The results of cellular and molecular experiments showed that JSCBR can effectively reduce the protein expression of ASC, caspase-1, IL-1β, and NRLP3 in monosodium urate-induced THP-1 cells, which indicated that JSCBR mediated inflammation in gouty arthritis by inhibiting the activation of NOD-like receptor signaling pathway.ConclusionThus, the integrated approaches adopted in the present study could contribute to simplifying the complex system and providing directions for further research of JSCBR.

Chronic tophaceous gout manifesting with bilateral diffuse pedal swelling: Cytology revisited with an update in its list of differentials

Gout, a disorder of purine metabolism, presents with acute or chronic arthritis and deposition of urate crystals in connective tissue and kidneys. Rarely, patients progress into chronic tophaceous gout (CTG). We emphasize on a 74-year-old male patient, who developed multiple gouty tophi over both his hands. In addition, both his feet were diffusely swollen. On detection of characteristic urate crystals from both his hands and feet lesions, the diagnosis of CTG was confirmed.

Influence of metabolic syndrome on the result of ischemic cardioembolic stroke due to atrial fibrillation

Metabolic syndrome is a complex of metabolic, hormonal, and clinical disorders, which are based on insulin resistance and compensatory hyperinsulinemia, abdominal obesity, disorders of lipid, purine metabolism, and arterial hypertension, is a combination of factors, each of which, both individually and in combination with others, has a significant effect on the risk of occurrence and the characteristics of the course of cardiovascular diseases, in particular ischemic strokes. The clinical feature of metabolic syndrome is the frequent development of paroxysms of atrial fibrillation, as a manifestation of the late stages of "hypertensive heart", which is illustrated in a number of large-scale population studies on the relationship between metabolic syndrome and the risk of atrial fibrillation. Our work raises the question of the features of the relations between metabolic syndrome and ischemic stroke caused by atrial fibrillation. Information concerning the qualitative and quantitative characteristics of the components of the metabolic syndrome with a breakdown of the clinical features of ischemic cardioembolic stroke in persons with the pathology under discussion, their natural course, the prognosis of the outcome, and sensitivity to treatment is very low. The article presents the results of the analysis of factors that make it possible to predict the course and outcome of acute ischemic stroke caused by atrial fibrillation against the background of metabolic syndrome. In order to determine the prognostic criteria for the outcome of cardioembolic stroke, 86 patients were examined, 41 patients were diagnosed with a cardioembolic stroke on the background of metabolic syndrome, 45 patients with cardioembolic stroke without metabolic syndrome. The analysis was based on the construction of correlation pleiades. A similar factor structure of indicators in both studied groups of patients with cardioembolic stroke indicates the same nature of changes in the state against the background of acute vascular catastrophe. A more severe course of the disease, based on the data of correlation analysis and data obtained by comparing indicators, is noted in the presence of the metabolic syndrome. Prognostically significant factors that allow predicting the course and outcome of cardioembolic stroke are the degree of a motor deficit on a five-point scale, total cholesterol, high-density lipoproteins, blood glucose, persistent atrial fibrillation, degree of stenosis of the internal carotid arteries, CHA2DS2-VASc scale indices.

Менопаузальный метаболический синдром и риски назначения менопаузальной гормональной терапии. Пути решения

Climacteric is a physiological period of woman’s life starting from the decline in ovarian activity until the end of ovarian function. This period is commonly accompanied by the development of menopausal metabolic syndrome characterized by the increase in visceral fat mass, insulin resistance, and hyperinsulinemia which result in the disorders of carbohydrate, lipid, and purine metabolism. This paper reviews the factors increasing the risk of metabolic syndrome during menopause. Diagnostic techniques for metabolic syndrome are described. Treatment approaches to menopausal metabolic syndrome, the potentialities and specifics of menopausal hormone therapy (MHT), its anticipated effects are discussed. The difficulties with MHT are accounted for by the lack of an optimal medication which will maintain the functioning of cardiovascular system, skeletal system, brain, and optimal weight and also has a minimal risk of side effects and complications. Meanwhile, adequate MHT for climacteric disorders in perimenopausal and early postmenopausal women is an effective and safe treatment for menopausal metabolic syndrome considered as a prerequisite for cardiovascular diseases and type 2 diabetes. KEYWORDS: menopause, climax, metabolic syndrome, obesity, hypertension, diabetes, menopausal hormone therapy, venous thromboembolism. FOR CITATION: Esedova A.E., Urudzheva N.G., Il’ina I.Yu. Menopausal metabolic syndrome and the risks of menopausal hormone therapy: the solutions. Russian Journal of Woman and Child Health. 2020;3(4):260–266. DOI: 10.32364/2618-8430-2020-3-4-260-266.

Purine dysmetabolism in esophageal cancer

Objective: to assess the state of purine metabolism in patients with esophageal cancer, to establish the clinical and pathogenetic significance of the identified changes. Material and methods. A total of 41 patients with esophageal cancer (all men) aged from 43 to 83 years (mean age 60 years) were under observation. Adenocarcinoma was diagnosed in 39% of the patients, squamous cell carcinoma — in 61%, tumor invading into the diaphragm was found in 10% of cases, in the spleen — in 7%, lymph nodes metastasis occurred in 12% of cases, in distant organs — in 32%. The ratio of 1B, 2A, 2B, 3A and 4 stages of the disease was 1:8:4:2:7. The levels of products of purine metabolism — uric acid, oxypurinol, adenine, guanine, xanthine, hypoxanthine, xanthine oxidase, xanthine deaminase, adenosine deaminase, and 5' nucleotidase activities — were studied in blood serum. Results. Purine dysmetabolism is observed in all patients with esophageal cancer in the form of increased levels of uric acid and oxypurinol levels in the blood, xanthine oxidase, and adenosine deaminase activity, which is observed in 83–100% of the examined individuals. Changes in purine metabolism are associated with the presence of hyperuricemia (>420 µmol/l), detected in 63% of cases, with the severity of the tumor process, the germination of neoplasm in the spleen, para-aortic lymph nodes, liver, and skeletal muscle. Hyperuricemia has a negative impact on the survival of patients, and a high level of adeninemia has a predictive negative value. Conclusion. Сhanges in the purine metabolism are involved in the pathogenetic constructs of esophageal cancer, reflect the peculiarities of the tumor process, and in the future, medical technology can be developed for treating patients with esophageal cancer with purine metabolism disorders.

Efficiency estimation of diet therapy with protein component modification in patients with obesity and purine metabolism disorder

The development of a personalized nutritional approach to diet therapy for patients with obesity and hyperuricemia, aimed at increasing the treatment effectiveness of these patients, is an urgent task. The aim: to assess the impact of nutritional approach with a modification of the protein component on body composition and biochemical parameters in patients with obesity and purine metabolism disorder. Material and methods. A randomized controlled trial was conducted, and included 50 patients (average age 46.9±2.5 years) with obesity and purine metabolism disorder. All patients were divided into two groups of 25 people. Within 2 weeks patients of group 1 received the main version of a standard low-calorie diet (1730 kcal, protein - 87.4 g, fat - 61.4 g, carbohydrates - 207 g). Group 2 received a personalized version of the diet (2125 kcal, protein - 100.2 g, fat - 75.9 g, carbohydrate - 260 g) with the modification of the protein component: protein content of at least 90 g per day, restriction of animal products containing a high purine load. Results and discussion. During diet therapy the decrease in fat mass in group 1 patients averaged 4.4%, visceral fat area - 8.6% (p<0.05) and in patients of group 2 - 6.9 and 9.1% respectively (p<0.05). During treatment a significant decrease in muscle mass was observed in group 1 at average 3.9% (p<0.05), and in group 2 on the basis of personal nutritional approach there was a slight decrease in muscle mass at average of 1.5%. After treatment patients of the two groups showed improvement in a number of indicators of lipid and carbohydrate metabolism: a significant decrease (p<0.05) of glucose, total cholesterol, LDL cholesterol and triglycerides in blood serum by 18.2-19.1, 23.2-23.6, 24.2-25.0 и 28.5-30.4%. However, patients in group 1 showed a slight decrease in uric acid in blood serum at average 7.6%, and patients in group 2 who received a personal nutritional approach with a modification of the protein component showed a significant decrease in uric acid at average of 12.5% (p<0.05). Conclusion. The obtained data indicate the need for a personal nutritional approach with a modification of the protein component in patients with obesity and purine metabolism disorder, which will prevent the development and progression of complications associated with obesity.

HYPERTENSION MANAGEMENT IN METABOLIC SYNDROME

Hypertension is one of the key risk factors for cardiovascular morbidity and mortality. Metabolic syndrome (synonyms: syndrome X, insulin resistance syndrome) is characterized by increased visceral fat mass, decreased sensitivity of peripheral tissues to insulin (insulin resistance) and hyperinsulinemia, which cause disorders of carbohydrate, lipid, and purine metabolism. Hypertension is an integral component of the metabolic syndrome. The severity of hypertension in patients with metabolic syndrome is higher in comparison with patients without metabolic disorders. In patients with metabolic syndrome, the probability of cardiac and brain damage increases fivefold, kidney damage threefold, and the vessels twofold. The presence of diabetes reduces the likelihood of achieving effective control of blood pressure by 1.4 times, hypercholesterolemia — by 1.5 times, obesity — by 1.7 times. In the presence of any three factors, the effectiveness of treatment is reduced twofold. In this article, approaches to the management of patients with hypertension and metabolic syndrome, aspects of non-drug therapy, target blood pressure levels, and the choice of drugs are presented in accordance with evidence-based medicine and current recommendations.

Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior

Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ Tcells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ Tcells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ Tcell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ Tcells. Our study implicates a critical link between a purine metabolic disorder in CD4+ Tcells and stress-driven anxiety-like behavior.

Gout.

Gout is a chronic disease caused by monosodium urate (MSU) crystal deposition. Gout typically presents as an acute, self-limiting inflammatory monoarthritis that affects the joints of the lower limb. Elevated serum urate level (hyperuricaemia) is the major risk factor for MSU crystal deposition and development of gout. Although traditionally considered a disorder of purine metabolism, altered urate transport, both in the gut and the kidneys, has a key role in the pathogenesis of hyperuricaemia. Anti-inflammatory agents, such corticosteroids, NSAIDs and colchicine, are widely used for the treatment of gout flare; recognition of the importance of NLRP3 inflammasome activation and bioactive IL-1β release in initiation of the gout flare has led to the development of anti-IL-1β biological therapy for gout flares. Sustained reduction in serum urate levels using urate-lowering therapy is vital in the long-term management of gout, which aims to dissolve MSU crystals, suppress gout flares and resolve tophi. Allopurinol is the first-line urate-lowering therapy and should be started at a low dose, with gradual dose escalation. Low-dose anti-inflammatory therapies can reduce gout flares during initiation of urate-lowering therapy. Models of care, such as nurse-led strategies that focus on patient engagement and education, substantially improve clinical outcomes and now represent best practice for gout management.

“Surgical management of unusual large tophi in chronic tophaceous gout: A case report”

Gout is a disorder of purine metabolism a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot, and swollen joint. Pain typically comes on rapidly, reaching maximal intensity in less than twelve hours. The first metatarsophalangeal joint is affected in about half of cases. It may also result in tophi, renal stones, or urate nephropathy.1 Commonly, but very large tophi are unusual in chronic gout. Here we present 52 years male patient presenting with unusually large tophi over bilateral foot, with raised serum uric acid levels. In a untreated cases of chronic gout, patients can develop severe destructive poly articular involvement and tophi. Treatment aims at control of serum uric acid levels which can cause regression of tophi. And surgical excision of very large tophi. Keywords: Gout, Arthritis, Tophi, Surgical excision.

Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency

BackgroundHPRT deficiency is a rare disorder of purine metabolism whose natural history is not fully understood. No optimal management recommendations exist. The objective of the present study is to characterize a large cohort of patients with HPRT deficiency, comparing Lesch-Nyhan Disease (LND) and its attenuated variants, with the purpose of helping clinicians in disease management and prognostic definition. MethodsGenetic and clinical features of French and Italian patients with a confirmed diagnosis of HPRT deficiency were collected. ResultsA hundred and one patients were studied, including 66 LND, 22 HND (HPRT-related Neurological Dysfunction) and 13 HRH (HPRT-Related Hyperuricemia) patients. The clinical manifestations at onset were not specific, but associated with an orange coloration of diapers in 22% of patients. The overall neurological involvement was more severe in LND than in HND patients. Behavioural disturbances were not limited to self-injuries and were not exclusive of LND. Median age of involuntary movements and self-injuries appearance in LND was 1.0 and 3 years, respectively. Renal manifestations (66.3% of patients) occurred at any age with a median onset age of 1.1 years, while gout (25.7% of patients) appeared later in disease course (median onset age 18 years) and was more frequent in attenuated variants than in LND. HPRT activity and genotype showed a significant correlation with the severity of the neurological disease. On the contrary, there were no significant differences in the development of nephropathy or gout. For the treatment of neurological aspects, botulinum toxin injections, oral or intrathecal baclofen and gabapentin were partially efficacious and well tolerated, while deep brain stimulation was associated to a worsening of patients' condition. ConclusionsThe present study improves the knowledge of the natural history of HPRT deficiency and could represent a starting point for the development of future management guidelines.

Malignant hyperthermia in Lesch-Nyhan disease

Lesch-Nyhan disease is a heritable disorder of purine metabolism. Inheritance is X-linked and the disease occurs almost exclusively in males.

Novel xanthine oxidase-based cell model using HK-2 cell for screening antihyperuricemic functional compounds

Hyperuricemia is a metabolic disease caused by disorders of purine metabolism, the prevalence of which has increased worldwide. Here, a cell model for high uric acid production was established in vitro employing cultured human kidney cells (HK-2 cells), and its molecular basis was analyzed using gene expression profile. High performance liquid chromatography (HPLC) was used to monitor the content of metabolites in cell culture media. Adenosine addition was found to induce HK-2 cells to produce uric acid precursors (inosine and hypoxanthine). Furthermore, the cell model was verified by confirming the antihyperuricemic effect of the widely used antihyperuricemic drugs allopurinol, probenecid, and febuxostat, as well as reported bioactive peptides and amino acids, encompassing glutathione, tryptophan and carnosine, which significantly reduced uric acid production in the HK-2 cells (p < 0.05). RNA-Seq technology was used to perform a wide transcriptome analysis of the hyperuricemic cell model, and the results demonstrated that it has the potential to be used as a rapid and valid in vitro model to screen antihyperuricemic compounds that mimics in vivo cell growth patterns.

Prevalence of Hyperuricemia and its Correlation with Serum Lipids and Blood Glucose in Physical Examination Population in 2015 - 2018: a Retrospective Study.

Hyperuricemia (HUA) is a metabolic disease caused by a disorder of purine metabolism, which increases the risk of cardio-cerebrovascular disease. Serum lipids and blood glucose are risk factors for metabolic syndrome. Thus, this study aimed to assess the prevalence of HUA and its relationship with serum lipids and blood glucose. A total of 59,074 cases (32,623 males and 26,451 females) from three hospitals in Lanzhou city from January 2015 to December 2018 were grouped according to serum uric acid (SUA) level to analyze the differences in age, total cholesterol (TC), triacylglycerol (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting blood glucose (FBG), creatinine (Cr), and blood urea nitrogen (BUN). The changes of prevalence of HUA among different age and gender groups was analyzed. Pearson's correlation analysis was used to analyze the correlation of SUA level with clinical indicators. The risk factors of HUA were analyzed by using binary logistic regression analysis. ROC curve was used to analyze the independent risk factors of elevated SUA. The overall prevalence rate of HUA was 19.87% and the prevalence rate of males was significantly higher than that of females (28.35% vs. 9.41%, χ2 = 3,289.143, p < 0.01). The prevalence rates of HUA from 2015 - 2018 were 19.54%, 19.31%, 18.64%, and 21.81%, respectively. Compared with the normal SUA group, TC, TG, and LDL significantly increased in the HUA group. The correlation analysis showed that SUA was negatively correlated with gender and HDL, and positively correlated with age, FBG, TC, TG, and LDL. The logistic regression analysis revealed that TG, TC, and LDL were risk factors for HUA. The ROC curve analysis showed that the risk of HUA significantly increased when TG was above 1.645 mmol/L. The overall prevalence of HUA in physical examination population has generally been at a high level in the past 4 years. Serum lipids and blood glucose may be independent risk factors for predicting HUA.

Взаємозв’язок порушень ліпідного й пуринового обміну в пацієнтів з гіпертонічною хворобою та інсулінорезистентністю

Взаємозв’язок порушень ліпідного й пуринового обміну в пацієнтів з гіпертонічною хворобою та інсулінорезистентністю

САНАТОРНО-КУРОРТНОЕ ЛЕЧЕНИЕ ДЕТЕЙ С ЭКОЛОГООТЯГОЩЁННЫМ ПИЕЛОНЕФРИТОМ, АССОЦИИРОВАННЫМ С НАРУШЕНИЯМИ ПУРИНОВОГО ОБМЕНА

Objective: To study the effectiveness of the treatment on the basis of drinking mineral waters, carbon dioxide baths and rational pharmacotherapy in children with environmental burdened chronic pyelonephritis, associated with violations of purine exchange, in the conditions of the Zheleznovodsk resort. Methods: Fifty children with chronic pyelonephritis with an environmental burdened anamnesis of 11-14 years were under observation. The method of simple randomization was formed two groups: control (25 people), which received traditionally accepted treatment at the Zheleznovodsk resort (dietary nutrition, therapeutic gymnastics, internal intake of the little mineralized mineral water of the Smirnov spring, carbon dioxide mineral baths), and the main one (25 people), where children received additional drug therapy with herbal medicine Canefron N. All patients were prescribed: ultrasound examination of the kidneys, clinical and biochemical blood and urine tests. Results: Comparative analysis showed that children of main group had a reduction of pain and dysuric syndromes, and in control group pain syndrome by the end of treatment persisted in 8% of cases, slightly more often preserved dysurian (16%) and asthenonneurotic (16%) syndromes. In children of main group, there was a significant decrease in daily oxaluria (by 39.2%; р&lt;0,01), an increase in the rate of glomerular filtration (by 11.93%), which was statistically significant in relation to the data in control group, where there was only a tendency to improve kidney function. According to the data of the long-term results in children of main group, the number of relapses decreased by 2.9 times (p&lt;0.01), while in patients of control group there was only a tendency to decrease this indicator. Conclusion: Comprehensive balneo- and drug therapy in children with environmental burdened pyelonephritis, associated with purine metabolism disorders, contribute to statistically significant to increase clinical effectiveness, ensures the long-term preservation of the achieved therapeutic effect. Keywords: Children, environmental burdened pyelonephritis, mineral waters, resort treatment.

Нарушения пуринового обмена: диагностика и терапия (клиническая лекция)

Нарушения пуринового обмена: диагностика и терапия (клиническая лекция)

Trastornos hereditarios del metabolismo de las pirimidinas y las purinas asociados a discapacidad intelectual

Actualizar al lector en los trastornos hereditarios del metabolismo de pirimidinas y las purinas relacionadas con discapacidad intelectual. Materiales y métodos: Se analizó la literatura disponible de los últimos 60 años en las bases de datos BBCS-LILACS, PubMed, IB-PsycINFO, IB-SSCI, IB-SciELO, Scopus y Science Direct. Se seleccionaron 51 referencias, con base en la calidad de la evidencia presentada por las mismas. Resultados: Se obtuvo información pertinente relacionada con los objetivos propuestos en la presente revisión, por lo cual puede clasificarse en dos secciones a saber: alteraciones del metabolismo de las pirimidinas asociadas a retardo mental, alteraciones del metabolismo de las purinas asociadas a retardo mental. Conclusión: Los trastornos hereditarios del metabolismo de las purinas y pirimidinas son un grupo creciente de enfermedades, con las cuales el personal de la salud debe familiarizarse ante la necesidad de un abordaje clínico y de laboratorio específicos. Se hace necesario buscar la posible relación con este tipo de enfermedades en los pacientes que presenten retardo mental, con miras a ofrecer asesoría genética que beneficie a las familias de los pacientes que las sufren.

Renal involvement in hyperuricemia

Hyperuricemia is a condition characterized by elevated levels of serum uric acid (SUA) in the blood. It is a chronic metabolic disorder due to purine metabolism disorders that may be primary or induced by other pathogenetic disorders. It is an important risk factor for the development of cardiovascular (CHD) and chronic kidney disease (CKD). The meta-analysis of two studies with adjusted risk assessments indicates that hyperuricemia is independently associated with an increased risk of peripheral neuropathy in patients with type 2 diabetes. The decrease in SUA values with xanthine oxidase inhibitors has been associated with a favorable response in regard to arterial blood pressure, arterial rigidity, vascular wall thickening, oxidative stress, left ventricular hypertrophy and renal function. The development of hyperuricemia occurs by way of two main mechanisms: 1. Increased purine synthesis; 2. Decreased kidney elimination. The subject of this work is the early and specific manifestations of hyperuricemia, mechanisms of kidney involvement and methods of treatment depending on the degree of glomerular filtration. Together with hypertension, obesity, dyslipidemia and insulin resistance, hyperuricemia is an invariable part of the metabolic syndrome and increasing cardiovascular risk that impacts renal function. Any increase in SUA by 60 μmol/L significantly increases cardiovascular mortality and overall mortality, and this dependence remains significant after considering the impact of all potential factors. Timely and adequate treatment of hyperuricemia leads to improvement of endothelial function, decrease of elevated blood pressure, retardation of the progression of renal involvement and prevention of the worsening of glomerular filtration rate.

50 Years Ago in The Journal Of Pediatrics: A New Disorder of Purine Metabolism with Behavioral Manifestations

50 Years Ago in The Journal Of Pediatrics: A New Disorder of Purine Metabolism with Behavioral Manifestations