Ovariectomy in the rat induces a rapid increase in the urinary excretion of hydroxylysine glycosides and non-reducible crosslink residues

The ovariectomized rat is the most commonly used animal model of human postmenopausal osteoporosis, exhibiting a high rate of bone turnover with resorption exceeding formation. At present, bone turnover is quantified directly by dynamic histomorphometry. The aim of the present study was to determine whether the measurement of the urinary output of some specific bone collagen catabolites — pyridinolines and hydroxylysine glycosides — could be used to indirectly monitor the initial phase of bone turnover increase in ovariectomized 90-day-old rats. Ninety-day-old female rats were randomly divided into three groups (n=6): ovariectomized, sham-operated and non-treated controls. Urine samples (24 h) were collected 6 days before surgery and twice weekly for the 4 weeks following ovariectomy. Urinary excretion of pyridinoline (PYD), deoxypyridinoline (DPD), glucosyl-galactosyl-hydroxylysine (GGHYL) and galactosyl-hydroxylysine (GHYL) were measured. As expected, ovariectomy was associated with a significant decrease in bone mineral density in both the proximal tibial and distal femoral metaphysis. Compared with both sham-operated and control animals, ovariectomized rats showed significant increases in PYD, GGHYL and GHYL urinary output 8 days after surgery and in DPD output after 15 days. These changes were maintained throughout the study. The results confirm that measurement of the urinary excretion of pyridinolines and hydroxylysine glycosides represents a powerful tool for detecting the onset of bone turnover in ovariectomized 90-day-old rats.     

Normal sperm parameters per se do not reliably account for fertility: A case–control study in the real-life setting

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.     

Rationale and design of the Kidney Precision Medicine Project

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Effects of intravenous verapamil on left ventricular relaxation and filling in stable angina pectoris

Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right- and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 +/- 22 to 117 +/- 16 mm Hg, p less than 0.01) and the end-systolic pressure/volume ratio (2.4 +/- 1.3 to 1.6 +/- 0.5 mm Hg/ml, p less than 0.05), and increased LV end-diastolic (13 +/- 4 to 16 +/- 4 mm Hg, p less than 0.02) and pulmonary capillary pressures (10 +/- 5 to 12 +/- 5 mm Hg, p less than 0.005). Despite such negative inotropic effects, cardiac index increased (3.4 +/- 0.7 to 3.9 +/- 0.6 liters/min/m2, p less than 0.02). The time constant of isovolumic relaxation shortened (63 +/- 14 to 47 +/- 9 ms, p less than 0.02); peak filling rate increased (370 +/- 155 to 519 +/- 184 ml/s, p less than 0.001; 2.6 +/- 1.1 to 3.3 +/- 0.9 end-diastolic counts/s, p less than 0.02; and 4.1 +/- 1.6 to 5.5 +/- 1.5 stroke counts/s, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)