Mitochondrial function and mitochondrial DNA in a series of 64 patients suspected of having mitochondrial myopathy

Biochemical results concerning 64 patients suspected of mitochondrial myopathies are presented. Four clinical groups were studied including 21 encephalomyopathies, 42 ocular myopathies, 8 isolated myopathies and 3 cardiomyopathies. In 26 cases, the coexistence of a normal mitochondrial DNA and a mutated mitochondrial DNA (heteroplasmy) was found (19 simple deletions, 4 multiple deletions and 3 punctual mutations) and all cases presented with ocular disorders (excepted 2 cases with MERRF). Furthermore, 1 complex I deficiency (1 ocular myopathy), 1 complex IV deficiency (1 adult encephalomyopathy type Leigh), 3 complexes I + IV deficiencies (2 cases with a cardiomyopathy and 1 familial MELAS) and 2 pyruvate (1 adult from of Leigh's encephalomyopathy) dehydrogenase deficiencies (clinically and genetically different) did not show evidence of mitochondrial DNA mutation.     

Kearns-Sayre syndrome with sideroblastic anemia: molecular investigations.

The progressive syndrome of Kearns-Sayre has been studied at the clinical, biochemical and genetic levels in a patient. Clinical arguments suggest an evolution from Pearson's disease to Kearns-Sayre syndrome. The respiratory chain activities were low, and Southern blot analysis, together with gene sequencing, showed a heteroplasmic deletion of 7767 base pairs in a significant proportion of the mitochondrial DNA in different tissues. Protein synthesis studies on lymphoblasts did not reveal any translation of the new reading frame created by the deletion, although the corresponding deleted mitochondrial DNA sequence is transcribed.     

Reversal of postmenopausal vertebral bone loss by oestrogen and progestogen: a double blind placebo controlled study

Because of uncertainty about the place of hormones in the treatment of postmenopausal bone loss vertebral and forearm bone loss was measured by absorptiometry in early postmenopausal women before and after continuous or sequential treatment with combined oestrogen and progestogen in a double blind placebo controlled trial. Treatment with hormones significantly reversed the vertebral bone loss. The net gain in vertebral bone density amounted to 6.4% a year with continuous supplementation and 5.4% a year with sequential supplementation; the net gain in forearm bone density was lower (3.6% with continuous and 3.7% with sequential supplementation). Before a policy of supplementation with hormones can be recommended to all postmenopausal women with the aim of reducing the incidence of vertebral crush fractures further studies with different doses and combinations of hormones, administered over several years, are needed.     

Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A.

BACKGROUND: Major depressive disorder (MDD) shows increased coronary artery disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men; CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients. METHODS: We measured fasting am serum CRP (high sensitivity, CRP(hs)) and SAA in 18 unmedicated, remitted women with MDD (mean age 41 +/- (SD)12, body mass index (BMI) 25.2 +/- 4.1 kg/m(2)) and 18 BMI-matched healthy control subjects (age 36 +/- 10, BMI 25.3 +/- 3.8 kg/m(2)) on 2 separate occasions, > or = 6 days apart. RESULTS: Repeat SAA and CRP(hs) measurements strongly correlated across study days (SAA: r = .83, p < .001; CRP(hs): r = .94, p < .001). Both SAA (5.30 +/- 3.39 vs. 2.84 +/- 1.87 mg/L, p < .005) and CRP(hs) (3.23 +/- 3.17 vs. 1.12 +/- 1.45 mg/L; p < .01) were significantly elevated in MDD women versus controls. CONCLUSIONS: Elevated SAA and CRP(hs) in remitted, unmedicated women with MDD indicate a pro-inflammatory state unrelated to current depressive symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms may in part underlie findings of increased CAD risk in MDD.     

Chronic Childhood Stress: Psychometric Properties of the Chronic Stress Questionnaire for Children and Adolescents (CSQ-CA) in Three Independent Samples

Stress in children and adolescents is common and related to many developmental problems. However, most studies have made no distinction between temporary or chronic stress due to the lack of a suitable questionnaire. This study tested the factor structure, reliability and validity of the 17-item self-report Chronic Stress Questionnaire for Children and Adolescents (CSQ-CA) in three samples, that is, 717 adolescents from the general population, 161 adolescents of parents with a severe chronic medical condition (CMC) like multiple sclerosis, and 113 adolescents with healthy parents. Results showed that a one-factor solution provided a reasonable fit overall. Reliability was good (α = .80 to .88). Convergent validity was supported by positive relations between total stress scores and internalizing and externalizing problem behaviors, experience of daily hassles, and maladaptive emotion regulation strategies and negative relations with quality of life, happiness, mindfulness, self-esteem, and coping skills. Adolescents from all samples, who themselves had a light CMC like asthma, showed higher chronic stress levels than those without a CMC. In line, adolescents of parents with a severe CMC reported more chronic stress than those of healthy parents, and adolescents with a chronic illness themselves and a parent with a chronic illness, showed the highest scores across the two family types. Overall, this study presents good psychometric properties of the first available measure of chronic stress in children and adolescents.     

Targeting the histone demethylase LSD1 prevents cardiomyopathy in a mouse model of laminopathy

LMNA mutations in patients are responsible for a dilated cardiomyopathy. Molecular mechanisms underlying the origin and development of the pathology are unknown. Herein, using mouse pluripotent embryonic stem cells (ESCs) and a mouse model both harboring the p.H222P Lmna mutation, we found early defects in cardiac differentiation of mutated ESCs and dilatation of mutated embryonic hearts at E13.5, pointing to a developmental origin of the disease. Using mouse ESCs, we demonstrated that cardiac differentiation of Lmna^H222P/+ was impaired at the mesodermal stage. Expression of Mesp1, a mesodermal cardiogenic gene involved in epithelial-to-mesenchymal transition of epiblast cells, as well as Snai1 and Twist expression, was decreased in Lmna^H222P/+ cells compared with WT cells in the course of differentiation. In turn, cardiomyocyte differentiation was impaired. ChIP assay of H3K4me1 in differentiating cells revealed a specific decrease of this histone mark on regulatory regions of Mesp1 and Twist in Lmna^H222P/+ cells. Downregulation or inhibition of LSD1 that specifically demethylated H3K4me1 rescued the epigenetic landscape of mesodermal Lmna^H222P/+ cells and in turn contraction of cardiomyocytes. Inhibition of LSD1 in pregnant mice or neonatal mice prevented cardiomyopathy in E13.5 Lmna^H222P/H222P offspring and adults, respectively. Thus, LSD1 appeared to be a therapeutic target to prevent or cure dilated cardiomyopathy associated with a laminopathy.     

Intermittent catheterization with single- or multiple-reuse catheters: clinical study on safety and impact on quality of life

International Urology and Nephrology - Intermittent catheterization (IC) is a proven effective long-term bladder management strategy for individuals who have lower urinary tract dysfunction. This...     

Altitude training causes haematological fluctuations with relevance for the Athlete Biological Passport

The impact of altitude training on haematological parameters and the Athlete Biological Passport (ABP) was evaluated in international‐level elite athletes. One group of swimmers lived high and trained high (LHTH, n = 10) for three to four weeks at 2130 m or higher whereas a control group (n = 10) completed a three‐week training camp at sea‐level. Haematological parameters were determined weekly three times before and four times after the training camps. ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (RET%), OFF score and the abnormal blood profile score (ABPS) were calculated using the Bayesian model. After altitude training, six swimmers exceeded the 99% ABP thresholds: two swimmers exceeded the OFF score thresholds at day +7; one swimmer exceeded the OFF score threshold at day +28; one swimmer exceeded the threshold for RET% at day +14; and one swimmer surpassed the ABPS threshold at day +14. In the control group, no values exceeded the individual ABP reference range. In conclusion, LHTH induces haematological changes in Olympic‐level elite athletes which can exceed the individually generated references in the ABP. Training at altitude should be considered a confounding factor for ABP interpretation for up to four weeks after altitude exposure but does not consistently cause abnormal values in the ABP. Copyright © 2014 John Wiley & Sons, Ltd.     

Mode of spironolactone anti-androgenic action: Inhibition of androstanolone binding to rat prostate androgen receptor

The anti-androgenic action of spironolactone was compared to that of cyproterone acetate and R 2956, two potent anti-androgenic steroids, on rat prostate, in vivo and in vitro. Like these compounds, spironolactone inhibits the formation of the specific androstanolonereceptor complex in cytoplasm and consequently in nuclei. Of its dethioacetylated metabolites, canrenone, but not canrenoate-K, exhibits the same in vitro action.