Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio‐ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (–2.9 and –2.5 mg/dl; both p < 0.001) and morning home systolic BP (–3.6 and –5.1 mm Hg; both p < 0.01) after 24 weeks'' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin‐creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (–20.8%; p = 0.021), but not febuxostat (–8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks'' treatment.     

Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor.

Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone that stimulates insulin secretion in the presence of glucose. Complementary DNA clones encoding human GIP were isolated from a library prepared with RNA from duodenum. The predicted amino acid sequence indicates that GIP is derived by proteolytic processing of a 153-residue precursor, preproGIP. The GIP moiety is flanked by polypeptide segments of 51 and 60 amino acids at its NH2 and COOH termini, respectively. The former includes a signal peptide of about 21 residues and an NH2-terminal propeptide of 30 amino acids. GIP is released from the precursor by processing at single arginine residues. There is a region of nine amino acids in the COOH-terminal propeptide of the GIP precursor that has partial homology with a portion of chromogranin A as well as pancreastatin.     

Lymphadenectomy along the middle colic artery in laparoscopic resection of transverse colon

BACKGROUND/AIMS: Although laparoscopic-assisted colectomy has been replacing open colectomy, dissection of lymph nodes along the main artery is sometimes difficult and dangerous in laparoscopic-assisted colectomy, especially, lymph nodes at the origin of the middle colic artery in laparoscopic resection of the transverse colon. METHODOLOGY: After the isolation of colon, meso-colon in both ends was excised. Then, the colon was rotated clockwise 90 degrees by centering at the base of the meso-colon. This procedure made it easier to isolate the anterior and posterior leaf of the meso-colon at its base. The middle colic artery was divided at the root with the dissection of lymph nodes around the base of the meso-colon. RESULTS: Successful lymphadenectomy of the lymph node along the origin of the middle colic artery was performed. Twelve patients with early transverse colon cancer underwent laparoscopic transverse colon resection using this method. CONCLUSIONS: This method may contribute to the easy and safe laparoscopic transverse colectomy by improving the limited view of the laparoscope and raises the possibility for laparoscopic resection of advanced colon cancer.     

Differences in composition of sweat induced by thermal exposure and by running exercise

To determine the differences in sweat composition between sweat induced by thermal stress alone and that induced by physical exercise, seven young healthy men first sat in a hot room and then performed running exercise. A 20-minute stay in a climate chamber at 40 degrees C resulted in a 5% reduction in body weight. The same body weight loss was induced by running exercise. Both sodium and chloride concentrations were much lower in the sweat induced by thermal exposure than that induced by the running exercise (p less than 0.01), while urea nitrogen and creatinine concentrations were significantly higher after thermal exposure than after the running exercise (p less than 0.01). Potassium concentrations did not differ significantly with either procedure. These findings suggest that sweat composition varies with the kind of induction and that more salt seems to be lost through exercise-induced sweating than by just sitting in a hot environment.     

Poor glycemic control and decreased renal function are associated with increased intrarenal RAS activity in Type 2 diabetes mellitus

Aims

The renin–angiotensin system (RAS) plays an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to investigate intrarenal RAS activity in patients with type 2 diabetes (T2DM).

Methods

We measured urinary angiotensinogen, a reliable biomarker of intrarenal RAS activity, in 14 controls without T2DM, 25 T2DM patients without nephropathy, 11 chronic kidney disease (CKD) patients without T2DM and 46 CKD patients with T2DM. Associations between urinary angiotensinogen and clinical parameters were examined.

Results

Compared with the controls, urinary [angiotensinogen:creatinine] were significantly higher in T2DM patients without nephropathy (4.70 ± 2.22 vs. 8.31 ± 5.27 μg/g, p = 0.037). Age, hemoglobin A1c (HbA1c) and fasting plasma glucose correlated significantly and positively with the log{urinary [angiotensinogen:creatinine]} (r = 0.632, p = 0.007; r = 0.405, p = 0.027; r = 0.583, p = 0.003, respectively) in T2DM patients without nephropathy. In contrast, the urinary [angiotensinogen:creatinine] were not significantly different between CKD patients with and without T2DM (22.7 ± 27.8 vs. 33.5 ± 40.8 μg/g, p = 0.740); although they were significantly higher when compared with non-CKD patients. In the CKD patients with T2DM systolic blood pressure, serum creatinine, estimated glomerular filtration rate and urinary [albumin:creatinine] correlated significantly with the log{urinary [angiotensinogen:creatinine]} (r = 0.412, p = 0.004; r = 0.308, p = 0.037; r = −0.382, p = 0.001; r = 0.648, p < 0.001, p < 0.001, respectively).

Conclusions

Our findings indicate that poor glycemic control is significantly associated with intrarenal RAS activity in T2DM patients without nephropathy, and that decreased renal function is significantly associated with intrarenal RAS activity in CKD patients with T2DM.     

Thoracoscopic versus open repair of esophageal atresia with tracheoesophageal fistula at a single institution

Purpose

The potential benefits of thoracoscopic repair (TR) of esophageal atresia and tracheoesophageal fistula (EA/TEF) in newborns are still unclear. Our aim was to define the criteria, perioperative outcome after undergoing TR versus open repair (OR) for EA/TEF.

Patients and methods

A retrospective chart review was conducted of 36 consecutive neonates who underwent EA/TEF repair between 2001 and 2012 in Shizuoka Children’s Hospital. Patients in this study were birth weight >2,000 g, and did not have severe cardiac malformations or chromosomal aberrations. Of the 26 newborns who met the selection criteria, 11 patients underwent attempts at TR compared to 15 patients who underwent OR. All cases were followed 1 year after operation at least.

Results

All 11 TR were successfully completed. There were no significant differences between intra- and perioperative complications in the two groups. Intraoperative EtCO₂ and arterial blood gases were not significantly different between the two groups. We did not found eating disorder, respiratory disorder, and failure of growth in all cases.

Conclusion

In our study, the thoracoscopic approach appeared to be favorable and safe for EA/TEF repair in carefully selected patients.