“Clinical features of women with gout arthritis.” A systematic review

Clinically, gout is generally considered as a preferential male disease. However, it definitely does not occur exclusively in males. Our aim was to assess differences in the clinical features of gout arthritis between female and male patients. Five electronic databases were searched to identify relevant original studies published between 1977 and 2007. The included studies had to focus on adult patients with primary gout arthritis and on sex differences in clinical features. Two reviewers independently assessed eligibility and quality of the studies. Out of 355 articles, 14 were selected. Nine fulfilled the quality and score criteria. We identified the following sex differences in the clinical features of gout in women compared to men: the onset of gout occurs at a higher age, more comorbidity with hypertension or renal insufficiency, more often use of diuretics, less likely to drink alcohol, less often podagra but more often involvement of other joints, less frequent recurrent attacks. We found interesting sex differences regarding the clinical features of patients with gout arthritis. To diagnose gout in women, knowledge of these differences is essential, and more research is needed to understand and explain the differences , especially in the general population

Reproductive Factors and Serum Uric Acid Levels in Females from the General Population: The KORA F4 Study

Hyperuricemia is associated with an increased risk of metabolic and cardiovascular diseases. There are pronounced sex differences in the levels of uric acid. It is largely unknown whether or not reproductive parameters which induce hormonal changes are responsible for this. We examined if there are associations between reproductive parameters and uric acid levels in a female population-based sample. In this cross-sectional analysis, data of 1530 women aged 32 to 81 years participating in the KORA F4 study, conducted between 2006 and 2008 in Southern Germany were used. Reproductive parameters were obtained by standardized interviews. Uric acid levels were tested by the uricase method. The whole study sample and stratified in pre- and postmenopausal women was analyzed. Menopausal status and earlier age at menarche were associated with higher serum uric acid levels (age-adjusted: p-values 0.003, <0.001 respectively; after multivariable adjustment, including BMI: p-values 0.002, 0.036). A history of oral contraceptive use showed an association with uric acid levels only after multivariable adjustment (p-value 0.009). Hot flushes showed an association with uric acid levels only after age-adjustment (p-value 0.038), but lost significance after adding other confounders. Other reproductive factors, including parity, current or ever use of hormone replacement therapy, current use of oral contraceptives, hysterectomy, bilateral oophorectomy, or depressive mood related to menopausal transition were not associated with uric acid levels. Postmenopausal status, earlier age at menarche and a history of oral contraceptive use were independently associated with higher serum uric acid concentrations in women from the general population. Further studies, especially longitudinal population-based studies investigating the relationship of female reproductive parameters with uric acid levels are necessary to confirm our findings

Catalytic activation of β-arrestin by GPCRs

β-arrestins are critical regulator and transducer proteins for G-protein-coupled receptors (GPCRs). β-arrestin is widely believed to be activated by forming a stable and stoichiometric GPCR-β-arrestin scaffold complex, which requires and is driven by the phosphorylated tail of the GPCR. Here we demonstrate a distinct and additional mechanism of β-arrestin activation that does not require stable GPCR-β-arrestin scaffolding or the GPCR tail. Instead, it occurs through transient engagement of the GPCR core, which destabilizes a conserved inter-domain charge network in β-arrestin. This promotes capture of β-arrestin at the plasma membrane and its accumulation in clathrin-coated endocytic structures (CCSs) after dissociation from the GPCR, requiring a series of interactions with membrane phosphoinositides and CCS-lattice proteins. β-arrestin clustering in CCSs in the absence of the upstream activating GPCR is associated with a β-arrestin-dependent component of the cellular ERK (extracellular signal-regulated kinase) response. These results delineate a discrete mechanism of cellular β-arrestin function that is activated catalytically by GPCRs