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Mechanical stress determines bone mass and structure. It is not known whether mechanical loading affects expression of bone regulatory genes in a combined deficiency of estrogen and vitamin D. We studied the effect of mechanical loading on the messenger RNA (mRNA) expression of bone regulatory genes during vitamin D and/or estrogen deficiency. We performed a single bout in vivo axial loading with 14 N peak load, 2 Hz frequency and 360 cycles in right ulnae of nineteen weeks old female control Wistar rats with or without ovariectomy (OVX), vitamin D deficiency and the combination of OVX and vitamin D deficiency (N = 10/group). Total bone RNA was isolated 6 hours after loading, and mRNA expression was detected of Mepe, Fgf23, Dmp1, Phex, Sost, Col1a1, Cyp27b1, Vdr, and Esr1. Serum levels of 25(OH)D, 1,25(OH) 2 D and estradiol were also measured at this time point. The effect of loading, vitamin D and estrogen deficiency and their interaction on bone gene expression was tested using a mixed effect model analysis. Mechanical loading significantly increased the mRNA expression of Mepe, and Sost, whereas it decreased the mRNA expression of Fgf23 and Esr1. Mechanical loading showed a significant interaction with vitamin D deficiency with regard to mRNA expression of Vdr and Esr1. Mechanical loading affected gene expression of Mepe, Fgf23, Sost, and Esr1 independently of vitamin D or estrogen, indicating that mechanical loading may affect bone turnover even during vitamin D deficiency and after menopause., (© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

A chromosomal abnormality in one of the fetuses of a monozygotic twin pregnancy is a rare phenomenon. In the prenatal unit of our cytogenetics laboratory we have recently come across two such heterokaryotypic twin pregnancies. In both cases ultrasound abnormalities were detected in one fetus of each twin pair. Chromosomal analysis showed that one twin pregnancy was discordant for trisomy 21 and the other for 45,X. Ultrasonographic examination suggested a monochorionic twin pregnancy in each case and DNA studies confirmed that both sets of twins were monozygotic. Both pregnancies were terminated. Biopsies taken from different sites of the placentas showed chromosomal mosaicism in both cases. There was no clear correlation between the karyotype found close to the site of the umbilical cord insertion in the placenta and the karyotype of the fetus. Sampling of amniotic fluid from both sacs is recommended in diamniotic twin pregnancies if one (or both) of the fetuses has ultrasound abnormalities, even if the twins are apparently monochorionic.

Pepsinogen A (PGA) and pepsinogen C (PGC) are negatively charged, low molecular weight (LMW) proteins with a striking difference in renal handling: PGA (molecular weight 43,500 daltons) shows a high fractional excretion while the fractional excretion of PGC (molecular weight 40,500 daltons) is low, presumably due to tubular reabsorption. As these data suggest a high glomerular sieving of pepsinogens, we assessed the glomerular sieving coefficient (GSC) of PGA, PGC and several other proteins from their renal extractions. For this purpose blood samples were obtained simultaneously from the aorta (A) and right renal vein (V) in nine patients undergoing an elective heart catheterization. After correction of A-V differences for diuresis with the A-V difference of transferrin, GSCs (+/- SEM) for PGA and PGC were 0.90 +/- 0.14 and 0.85 +/- 0.17, respectively, GSC of beta 2-microglobulin being 0.90 +/- 0.12. For albumin and IgG, known to have a low GSC, low values were found. It is concluded that the GSC of a LMW protein in man can be calculated from both its A-V difference over the kidney and the A-V difference of an inert marker with a GSC of 1, provided they are corrected by the A-V difference of an inert marker with a GSC of 0. Our results demonstrate that PGA and PGC are almost freely filtered through the glomerular basement membrane despite their size and negative net molecular charge.