Inhibition of adenosine deaminase and xanthine oxidase by valproic acid abates hepatic triglyceride accumulation independent of corticosteroids in female rats treated with estrogen-progestin.

Elevated circulating uric acid has been postulated to play an important pathophysiological role in estrogen-progestin combined oral contraceptive (COC)-induced hypertension and endothelial dysfunction. We hypothesized that disruption of glucoregulation and liver triglyceride (TG) accumulation induced by COC use would be abated by valproic acid (VPA) treatment through suppression of adenosine deaminase (ADA) and xanthine oxidase (XO) activities. Female Wistar rats aged 9-10 weeks were treated with a combination of estrogen-progestin COC steroids (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel; p.o.) with or without VPA (100.0 mg/kg; p.o.) daily for 6 weeks. The result shows that the disrupted glucoregulation and associated elevated hepatic ADA activity, plasma and hepatic XO activity, uric acid (UA), TG/HDL-cholesterol, total cholesterol, and malondialdehyde induced by COC treatment were attenuated by VPA treatment. However, VPA did not have any effect on plasma aldosterone, corticosterone, ADA, circulating and hepatic free fatty acid. Our results demonstrate that suppression of plasma and hepatic XO activities, along with hepatic ADA activity and UA by VPA treatment, protects against disrupted glucoregulation and increased liver TG by COC independent of elevated corticosteroids. The findings imply that VPA would provide protection against the development of cardiometabolic disorder via inhibition of the ADA/XO/UA-mediated pathway.

Association Between Low-Grade Inflammation and Hyperuricemia in Adults With Metabolic Syndrome in Yucatán, México.

BACKGROUND: Hyperuricemia (HUA) is commonly diagnosed among individuals with obesity, type 2 diabetes (T2D) and metabolic syndrome (MetS). Nevertheless, the association of HUA in individuals with MetS among the Mexican population is mostly unexplored. Low-grade inflammation has been postulated to have a key role in the pathogenesis of MetS and has been linked to insulin resistance (IR). However, it is uncertain whether HUA is associated with elevated levels of interleukin-6 and -10 (IL-6 and IL-10, respectively) and high-sensitivity C-reactive protein (hs-CRP) in individuals with MetS. Our main goal was to assess the values of inflammatory markers in a Mexican adult population without and with MetS and HUA. METHODS: A cross-sectional study including 250 adults (77 men, 173 women) was carried out at a tertiary hospital in Mérida, Yucatán, México. Serum levels of IL-6, IL-10 and hs-CRP were evaluated by an enzyme-linked immunosorbent assay. The association between different conditions and inflammatory markers was analyzed using the point-biserial correlation (rpb) among patients. RESULTS: IR was positively associated with higher levels of serum uric acid (SUA). Serum levels of IL-6 and hs-CRP were found to be significantly associated with MetS, HUA and combined clinical conditions of MetS and HUA in women. Inter-relationships were stronger in women than in men. CONCLUSIONS: An association between levels of IL-6 and hs-CRP in women with MetS and HUA was found. Therefore, screening and monitoring of SUA and these markers in patients with MetS may be an alternative for treatment of these metabolic conditions.

[Gout]. / La maladie goutteuse.

Gout is a chronic disease due to the deposition of monosodium urate microcrystals in joints and tissues. Its incidence and prevalence are increasing worldwide in close relation with the epidemic of obesity and metabolic syndrome. Gout is related to chronic hyperuricemia that should be treated to ensure the reduction or even the disappearance of acute attacks ("gout flares") and to reduce the size and number of tophi. If arthritis of the first metatarsophalangeal joint is the most typical form, other joints may be affected, including the spine. Demonstration of urate microcrystals arthritis allows diagnosis of gout but, in the absence of possibility of performing joint puncture, imaging may be useful for providing complementary diagnostic elements. Appropriate care is essential to reduce the number of flares and the evolution towards gouty arthropathy but also in terms of public health in order to reduce costs related to this pathology.

[Gout and Its Management in Clinical Practice]. / Die Gicht und ihr Management in der Praxis.

Gout and Its Management in Clinical Practice Abstract. Resolution of an acute attack is usually the prime objective in routine clinical management of gout. Crystal identification in synovial fluid by polarised light microscopy is considered the diagnostic gold standard. Imaging procedures such as high-resolution ultrasonography are also useful. Non-steroidal anti-inflammatory drugs, steroids and colchicine (not approved in Switzerland, available from pharmacies) are used to treat an acute gout attack. Just as important as the diagnosis and treatment of an acute attack is the long-term management of hyperuricaemia in order to prevent further gout attacks as well as possible renal, cardiac or metabolic complications. Therefore, patients with a confirmed diagnosis of gout should, apart from non-pharmacologic interventions, receive hypouricaemic therapy with a target uric acid level of <360 µmol/l (<6 mg/dl). Drugs of first choice are xanthine oxidase inhibitors. Achievement of the therapeutic objective should be periodically reviewed, adjusting therapy as necessary.

Uric acid is a key player in salt-induced endothelial dysfunction: the therapeutic role of Stigma maydis (corn silk) extract.

Hyperuricemia has been implicated in the pathogenesis and complications of cardiovascular diseases with associated elevated oxidant events. There is evidence that excessive salt intake results in cardiometabolic disturbances but the mechanism is elusive. Also, Stigma maydis (corn silk) is noted for its antioxidant properties among other beneficial roles. This study, therefore, aimed to establish the effect of high-salt diet (SD) on uric acid (UA) production and the role of S. maydis in salt-induced phenotypes. Four groups of randomly selected rats (n = 5) were fed with normal rat feed, corn silk extract (500 mg/kg), SD (8%) and corn silk extract plus high-salt feed. After 6 weeks of the experimental procedure, each animal was anesthetized by exposure to chloroform vapor and blood samples collected by cardiac puncture. Data were expressed in means ± SEM and p values <0.05 were accepted as significant. SD resulted in reduced plasma superoxide dismutase (SOD), nitric oxide (NO), and glutathione peroxidase (GPx) but not endothelial nitric oxide synthase. Also, plasma UA and vascular cell adhesion molecule-1 (VCAM-1) increased in the SD group compared with control. However, S. maydis extract in the SD-exposed group increased NO and GPx and not SOD. Also, S. maydis extract attenuated UA and VCAM-1. In conclusion, high-salt intake may initiate deleterious cardiovascular events through UA-dependent mechanism and S. maydis extract has therapeutic potential in high-salt-induced oxidative damage and/or UA-dependent endothelial pathologies.

[Light and Shadow of Hyperuricemia - Neuroprotection, Comorbidities and Therapeutic Strategies]. / Licht und Schatten der Hyperurikämie: Neuroprotektion, Komorbiditäten und Therapiestrategien໿.

Light and Shadow of Hyperuricemia - Neuroprotection, Comorbidities and Therapeutic Strategies Abstract. Hyperuricemia can lead to gout but also favor the appearance of comorbidities like hypertension, kidney insufficiency, type 2 diabetes, myocardial infarction and strokes. Uric acid does not only have, however, negative impact on the body, but seems to influence positively certain inflammatory and degenerative neurological diseases. The inflammatory reaction at the center of a gout attack is mediated by interleukin 1. Therefore, antagonists against interleukin 1 or IL-1 receptors can be used for treatment if colchicine, steroids or nonsteroidal anti-inflammatory drugs are ineffective or contraindicated. First-line drug for urate-lowering therapy is allopurinol that positively influences comorbidities as well.

Hand involvement in gout.

Damage to the hand in patients suffering from gout is rare and is often detected at an advanced stage. The main clinical manifestations are the appearance of subcutaneous tophi at the finger joints. Other clinical manifestations of osteoarticular, tendinous or neurological lesions have been described in the hand and are often difficult to diagnose. In the majority of cases, surgery and adequate medical care with a suitable anti-gout treatment will allow the patient to recover normal hand function. However, surgical treatment is rare and is only performed after several months of carefully adapted medical treatment. The purpose of this article is to present the various clinical forms of gout in the hand and their surgical management.

Prevalence and factors associated with hyperuricaemia in newly diagnosed and untreated hypertensives in a sub-Saharan African setting.

BACKGROUND: Few studies have evaluated the link between hyperuricaemia and cardiovascular disease in sub-Saharan Africa. AIMS: To assess the prevalence of and factors associated with hyperuricaemia among newly diagnosed treatment-naïve hypertensive patients in sub-Saharan Africa. METHODS: We performed a community-based cross-sectional study from January to December 2012 in Douala, Cameroon (Central Africa). We enrolled newly diagnosed treatment-naïve hypertensive patients, and excluded those with gout or a history of gout. Serum uric acid concentrations were measured by enzymatic colourimetric methods, and hyperuricaemia was defined as a serum uric acid concentration>70IU/mL. Fasting blood sugar concentrations, serum creatinine concentrations and lipid profiles were also measured. Logistic regression was used to study factors associated with hyperuricaemia. RESULTS: We included 839 newly diagnosed treatment-naïve hypertensive patients (427 women and 412 men; mean age 51±11 years; mean serum uric acid concentration 60.5±16.5IU/L). The prevalence of hyperuricaemia was 31.8% (95% confidence interval [CI] 28.7-34.9) and did not differ by sex (132 women vs. 135 men; P=0.56). Multivariable logistic regression identified age>55 years (adjusted odds ratio [AOR] 1.65, 95% CI 1.12-2.29), family history of hypertension (AOR 1.65, 95% CI 1.01-2.67), waist circumference>102cm in men or>88cm in women (AOR 1.60, 95% CI 1.12-2.29), low-density lipoprotein cholesterol>1g/L (AOR 1.33, 95% CI 0.97-1.82) and triglycerides>1.5g/L (AOR 1.63, 95% CI 1.01-2.65) as independently associated with hyperuricaemia. CONCLUSION: Hyperuricaemia is common among newly diagnosed treatment-naïve hypertensive patients in sub-Saharan Africa and is associated with some components of the metabolic syndrome.

Combination of hyperuricemia and metabolic syndrome is an independent and powerful predictor for left ventricular hypertrophy in rural Chinese.

OBJECTIVES: To investigate the influence of MetS (metabolic syndrome) in combination with hyperuricemia on left ventricular hypertrophy (LVH) in residents in the rural area of Northeast China. METHODS: We performed a cross-sectional baseline data analysis of 11,170 subjects (mean age: 54±11years) recruited from the rural area of China. Anthropometric indicators were measured according to standard methods. MetS was defined by the ATP III modified criteria. Hyperuricemia was defined according to sex-specific serum uric acid levels (SUA): SUA≥7.0mg/dL for male and≥6.0mg/dL for female. Four groups were listed: normouricemia non-MetS, hyperuricemia non-MetS, MetS normouricemia and hyperuricemia MetS. RESULTS: Left ventricular mass index for height(2.7) (LVMH(2.7)) in female was significantly higher in hyperuricemia MetS group than that in normouricemia non-MetS (52.43±16.60 vs. 40.04±10.72g/m(2.7), P<0.001) group. Similar result was observed in men (48.93±13.17g/m(2.7) vs. 43.63±11.90g/m(2.7), P<0.001). The result of multiple regression analysis indicated that hyperuricemia MetS group had higher risk of LVH than other three groups (OR: 3.427 for female, P<0.001, OR: 1.987 for male, P<0.001). Moreover, female subjects in MetS normouricemia group [OR (95% CI): 2.313 (1.991-2.686)] had greater risk of LVH than that in hyperuricemia non-MetS group [OR (95% CI): 1.917 (1.166-3.151)]. Hyperuricemia non-MetS was found to be significantly and independently associated with LVH in women, but not in men. CONCLUSION: Our study finds that the combination of hyperuricemia and MetS are independent and powerful predictor for LVH in rural area of Northeast Chinese. Women with MetS in combination with hyperuricemia have higher risk of LVH than men. It seems that MetS has greater effect on LVH than hyperuricemia does in women but not in men.