Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral,microarchitectural, biomechanical and matrix properties of rat bone

Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid–postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized–steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below −2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.     

Meta-analysis of telomere length in 19?713 subjects reveals high heritability,stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10⁻⁶¹) than father–offspring correlation (r=0.33; P-value=7.01 × 10⁻⁵), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10⁻⁵). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10⁻³⁰) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10⁻²³) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10⁻¹⁰). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.     

Elevated risk of adverse obstetric outcomes in pregnant women with depression

In this study, we evaluated the association between prenatal depression symptoms adverse birth outcomes in African–American women. We conducted a retrospective cohort study of 261 pregnant African–American women who were screened with the Edinburgh Postnatal Depression Scale (EPDS) at their initial prenatal visit. Medical records were reviewed to assess pregnancy and neonatal outcomes, specifically preeclampsia, preterm birth, intrauterine growth retardation, and low birth weight. Using multivariable logistic regression models, an EPDS score ≥10 was associated with increased risk for preeclampsia, preterm birth, and low birth weight. An EPDS score ≥10 was associated with increased risk for intrauterine growth retardation, but after controlling for behavioral risk factors, this association was no longer significant. Patients who screen positive for depression symptoms during pregnancy are at increased risk for multiple adverse birth outcomes. In a positive, patient-rated depression screening at the initial obstetrics visit, depression is associated with increased risk for multiple adverse birth outcomes. Given the retrospective study design and small sample size, these findings should be confirmed in a prospective cohort study.     

The γ-Glutamyl Cycle: A Possible Transport System for Amino Acids

Evidence is presented that rat kidney contains enzymes that catalyze the synthesis and utilization of glutathione; these reactions, which involve the uptake and release of amino acids from gamma-glutamyl linkage, constitute a cyclical process which is termed "the gamma-glutamyl cycle." The gamma-glutamyl cycle has properties that fulfill the requirements of an amino acid transport system. Thus, gamma-glutamyl transpeptidase may function in translocation and gamma-glutamylcysteine synthetase and glutathione synthetase may catalyze energy-requiring "recovery" steps in transport. These and other considerations suggest that glutathione serves a carrier function in amino acid transport.     

Diabetes and female sexual dysfunction: Moving beyond "benign neglect"

Female sexual response is a complex, nonlinear progression from desire to arousal and orgasm. Diabetes may affect all these, but it particularly affects arousal with decreased genital sensation and lubrication. Vaginal dryness and infections may lead to dyspareunia. Predictors of sexual dysfunction in women include depression. Neither age, duration of diabetes, glycemic control, nor complications predict sexual dysfunction in women as they do in men. Objective measures of decreased genital sensation or lubrication do not correlate with a subjective sense of female sexual arousal disorder. Low androgens and possibly estrogens may be etiologic, as may numerous medications used by patients with diabetes. Practitioners should recognize the high prevalence of female sexual dysfunction (up to 50%) and potential increase, in tandem with that of diabetes. In the absence of definitive treatment evidence, psychological counseling, improvised vaginal lubricants, and low doses of estrogens or androgens have been used to relieve the personal distress of female sexual dysfunction.     

Metabolism of 1-14C-ornithine and 1,4-14C-putrescine in chronically uremic and control rats

The metabolism of ornithine and putrescine was studied in vivo in chronically uremic and control rats. Rats were injected intraperitoneally with 1-¹⁴C-ornithine or 1,4-¹⁴C-putrescine and expired ¹⁴CO₂ was collected for 4 hr. After injection of 1-¹⁴C-ornithine, ¹⁴CO₂ expiration was decreased in uremic rats as compared to controls. Conversely, after 1,4-¹⁴C-putrescine injection, expiration of ¹⁴CO₂ was increased in uremic rats as compared to controls. Four hours after the injection of 1-¹⁴C-ornithine, there was more radioactivity in liver and muscle and less radioactivity in kidney of uremic rats as compared to the respective sources in control rats. In uremic rats, 4 hr after the 1,4-¹⁴C-putrescine injection, the radioactivity retained in the muscle and plasma was greater than in corresponding sources in control rats; whereas the radioactivity retained in uremic liver and kidney was similar to that of control rats. The greater putrescine-derived radioactivity retained in uremic tissues reflects either the retention of injected tracer compounds, or retention or decreased catabolism of putrescine metabolites. From ¹⁴CO₂ expiration data obtained, it appears that ornithine catabolism is reduced while putrescine catabolism is increased in uremia.