Febuxostat reduced serum UA levels more effectively than conventional therapy and might have a renoprotective effect in hyperuricemic patients with CKD. Further studies should clarify whether febuxostat prevents the progression of renal disease and improves the prognosis of CKD.

We examined changes in brain waves and blood levels of serum cortisol during yoga exercise in 7 yoga instructors and found that alpha waves increased and serum cortisol decreased. These two measures were negatively correlated (r = -.83). Comparison with a control group of nonpractitioners is desirable.

The molecular mechanism involved in pulmonary vascular disease (PVD) associated with congenital heart disease (CHD) remains uncertain. Evidence suggesting that angiotensin converting enzyme plays an important role in pulmonary vascular pathology led us to hypothesize that mast cell chymase, another angiotensin I converting enzyme, also had the potential to contribute to the development of PVD in CHD. Twenty-three patients 3 mo to 45 yr of age with atrial or ventricular or both septal defects with increased pulmonary arterial blood flow and pressure, with pulmonary vascular resistance ranging from 1.3 to 8.1 units/m(2), were studied. Mast cells and mast cell chymase were immunohistochemically identified in the lung biopsy tissues obtained during corrective surgery. There was a significant difference in numbers of total mast cells between patients (n = 23) and control subjects (n = 10) with normal pulmonary circulation (p < 0.01). Moreover, chymase-containing mast cells in the lung tissues of patients with CHD showed striking differences from those of control subjects. In the patients, 72% of lung mast cells contained chymase, compared with only 15% in control subjects (p < 0.0001). Chymase-containing mast cells predominantly appeared in the media and adventitia of vessel walls. Importantly, angiotensin II was immunohistochemically detected in perivascular lesions where chymase was present, but not in the lesions where chymase was sparsely seen. Furthermore, the number of chymase-containing mast cells was correlated with pulmonary vascular resistance (r = 0.64). These findings suggest a possible role of mast cell chymase in the development of early-stage PVD in patients with CHD.

Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility and secretion. We characterized the action of the 5-HT precursor 5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor activity in conscious mice. Fos immunoreactivity (IR), used as a marker of neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole mount preparations of the distal colon 90 min after an intraperitoneal injection of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a dose-related manner, with a peak response observed within the first 15 min postinjection. 5-HTP (0.5-10 mg/kg) dose dependently increased Fos expression in myenteric neurons, with a maximal response of 9.9 +/- 1.0 cells/ganglion [P < 0.05 vs. vehicle-treated mice (2.3 +/- 0.6 cells/ganglion)]. There was a positive correlation between Fos expression and fecal output. Of Fos-positive ganglionic cells, 40 +/- 4% were also pChAT positive and 21 +/- 5% were NADPH-diaphorase positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos expression were completely prevented by pretreatment with the selective 5-HT4 antagonist RS-39604. These results show that 5-HTP injected peripherally increases Fos expression in different populations of cholinergic and nitrergic myenteric neurons in the distal colon and stimulates propulsive colonic motor function through 5-HT4 receptors in conscious mice. These findings suggest an important role of activation of colonic myenteric neurons in the 5-HT4 receptor-mediated colonic propulsive motor response.

BackgroundAdvanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD).MethodsSkin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis.ResultsThirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004).ConclusionsTissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.