Metabolic flexibility in postmenopausal women: Hormone replacement therapy is associated with higher mitochondrial content, respiratory capacity, and lower total fat mass.

AIM: To investigate effects of hormone replacement therapy in postmenopausal women on factors associated with metabolic flexibility related to whole-body parameters including fat oxidation, resting energy expenditure, body composition and plasma concentrations of fatty acids, glucose, insulin, cortisol, and lipids, and for the mitochondrial level, including mitochondrial content, respiratory capacity, efficiency, and hydrogen peroxide emission. METHODS: 22 postmenopausal women were included. 11 were undergoing estradiol and progestin treatment (HT), and 11 were matched non-treated controls (CONT). Peak oxygen consumption, maximal fat oxidation, glycated hemoglobin, body composition, and resting energy expenditure were measured. Blood samples were collected at rest and during 45 min of ergometer exercise (65% VO2peak). Muscle biopsies were obtained at rest and immediately post-exercise. Mitochondrial respiratory capacity, efficiency, and hydrogen peroxide emission in permeabilized fibers and isolated mitochondria were measured, and citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD) activity were assessed. RESULTS: HT showed higher absolute mitochondrial respiratory capacity and post-exercise hydrogen peroxide emission in permeabilized fibers and higher CS and HAD activities. All respiration normalized to CS activity showed no significant group differences in permeabilized fibers or isolated mitochondria. There were no differences in resting energy expenditure, maximal, and resting fat oxidation or plasma markers. HT had significantly lower visceral and total fat mass compared to CONT. CONCLUSION: Use of hormone therapy is associated with higher mitochondrial content and respiratory capacity and a lower visceral and total fat mass. Resting energy expenditure and fat oxidation did not differ between HT and CONT.

Model-based roentgen stereophotogrammetric analysis of the surface replacement trapeziometacarpal total joint arthroplasty.

The primary aim of this clinical and radiostereometric study was to study the migration pattern of the surface replacement trapeziometacarpal joint prosthesis (SRTMTMC, Avanta®, San Diego, CA). The secondary aims were to assess patient-related outcomes and prosthesis survival 5 years after surgery. Ten patients received the prosthesis. Radiostereometric radiographs were obtained 6 weeks, 6 months, 1 year and 5 years post-operatively and were analysed using model-based software. All patients completed DASH and Nelson Hospital scores at these follow-ups. Mean translations varied between 0.0 and 0.5 mm after 5 years. Rotation values could be calculated in six patients and mean rotations varied between -0.3 and 2.3°, although the precision of rotation values seems to be poor. The 5-year survival rate was 80%. Mean pre-operative DASH and Nelson Hospital scores were 53 (SD 14) and 51 (SD 13), respectively. Six months post-operatively, the DASH and Nelson Hospital scores had both significantly improved to 25 (SD 20) and 74 (SD 18) and remained high after 5 years. Implant stability was good 5 years post-operatively, and early migration did not predict implant failure in this study. LEVEL OF EVIDENCE: IV.

Feasibility of model-based Roentgen Stereophotogrammetric Analysis to evaluate early migration of the trapeziometacarpal joint prosthesis.

BACKGROUND: The purpose of this study was to determine the feasibility of Roentgen Stereophotogrammetric Analysis (RSA) in total joint arthroplasty of the trapeziometacarpal (TMC) joint of the thumb. METHODS: In five cadaveric hands the TMC-joint was replaced by the Surface Replacement Trapeziometacarpal prosthesis (SR™ TMC prosthesis; Avanta, San Diego, CA) and tantalum beads of 0.8 mm were implanted for RSA. RSA radiographs in two directions were made in ten positions to calculate the measurement error. Migration values from zero are indicative for the measurement error. The number of detected markers was recorded. RESULTS: The accuracy analysis showed that for the translations the mean measurement error varied between 0.003 mm (SD 0.057) and 0.055 mm (SD 0.133). For the rotations values ranged from 0.034° (SD 1.759) to 0.502° (SD 1.617). CONCLUSIONS: RSA analysis of the SR™ TMC prosthesis is feasible. The measurement error is good for the translations but high for the rotations. The latter is due to the close position of the markers relative to each other. Level of evidence III.

The effects of antenatal betamethasone administration on fetal heart rate and behaviour depend on gestational age.

OBJECTIVE: We previously reported decreases in fetal heart rate (FHR) variability and body and breathing movements after maternal betamethasone administration. We now test the hypothesis that fetal responsiveness to betamethasone depends on the gestational age at which glucocorticoid therapy is started. DESIGN OF THE STUDY: 1-h recordings of FHR (n=350) and fetal movements (n=310) made during a 5-day period (days 0-4) were available for analysis. The recordings had been obtained from 63 pregnant women at high risk for preterm delivery who received betamethasone (two doses of 12 mg 24 h apart) between 26 and 34 weeks' gestational age (wGA). The response to betamethasone, i.e. the direction and magnitude of change in FHR and movement parameters compared with baseline (day 0), was studied in relation to gestational age at drug administration. RESULTS: Fetuses exposed to betamethasone at 29-34 wGA showed a decrease in FHR on day 1 (indicative of baroreceptor reflex), and reduced breathing activity and prolonged episodes of quiescence with a concomitant decrease in body movements on days 1 and 2. However, these changes were not observed if betamethasone administration occurred at 26-28 wGA. Betamethasone-induced reductions in FHR variability were similar in young and older fetuses. CONCLUSIONS: Age-related differential responsiveness to betamethasone was found for all studied fetal processes (body and breathing movements, FHR, and quiescence), except FHR variability. Our results suggest ontogenic changes in the mechanisms presumed to underlie these processes (glucocorticoid receptor (GR) maturation, cardiovascular and neuro-endocrine development).

In vitro evidence for differential involvement of CTGF, TGFbeta, and PDGF-BB in mesangial response to injury.

BACKGROUND: Connective tissue growth factor (CTGF) is a profibrotic growth factor, which is upregulated in wound healing and renal fibrosis, including anti-Thy-1.1 nephritis. The kinetics of CTGF mRNA expression in anti-Thy-1.1 nephritis suggested that CTGF regulation might contribute to glomerular response to injury downstream of transforming growth factor-beta (TGFbeta). In anti-Thy-1.1 nephritis the initial damage is followed by mesangial repair and limited sclerosis, which involves mesangial cell (MC) activation (alpha-smooth-muscle actin (alphaSMA) expression), proliferation, migration, and extracellular matrix production. The present in vitro study addresses the possible role of CTGF in these different aspects of mesangial response to injury, and how CTGF activity might relate to effects of TGFbeta and platelet-derived growth factor-BB (PDGF-BB). METHODS AND RESULTS: Immunostaining and ELISA showed that alphaSMA expression and transformation of MC into myofibroblast-like cells was induced by TGFbeta, but not affected by PDGF-BB, CTGF, or neutralizing anti-CTGF antibodies. [(3)H]thymidine incorporation and Ki67 staining demonstrated that, unlike PDGF-BB, neither CTGF nor TGFbeta induced the proliferation of MC. In contrast, both CTGF and TGFbeta induced MC migration, as evidenced by approximation of wound edges in scrape-wounded, non-proliferating rat MC monolayers. In addition, fibronectin expression was upregulated by both CTGF and TGFbeta, as measured by dot-blot analysis. Anti-CTGF completely blocked the effect of added CTGF. Moreover, anti-CTGF significantly reduced TGFbeta-induced increase in fibronectin. CONCLUSION: It thus appears that CTGF is specifically involved in a subset of the adaptive changes of MC involved in mesangial repair and sclerosis, which makes it an interesting candidate target for future intervention strategies.

Identification of human ccn2 (connective tissue growth factor) promoter polymorphisms.

BACKGROUND: Connective tissue growth factor (CCN2; CTGF) is a newly identified growth factor, which is involved in the regulation of wound repair and fibrosis. Because there is variation among individuals with respect to tissue response to injury, genetic factors might be involved in the final outcome of tissue repair or scarring. For example, polymorphisms in the promoter region of genes, such as those encoding transforming growth factor beta1 (TGF-beta1), interleukin 10 (IL-10), and tumour necrosis factor alpha (TNF-alpha), influence transcriptional responses and are thought to contribute to the dysregulation of these genes in pathological conditions. AIM: To investigate whether the promoter region of the ccn2 (ctgf) gene contains polymorphic sequences that might account for differential expression. MATERIALS/METHODS: Seventy seven human DNA samples were sequenced-45 were from healthy controls and 32 were from patients with ischaemic heart disease (IHD)-using M13 tailed sequence specific ccn2 (ctgf) primers for amplification of a 600 bp fragment upstream of the transcription start site. Amplicons were bidirectionally sequenced with a dye primer M13 forward and reverse sequencing kit. RESULTS: A C to G substitution was identified at position -132 in one of the patients with IHD. Moreover, in five of the 32 patients with IHD and in six of the 45 healthy controls, a G to C polymorphism was found at position -447. These substitutions at -132 and -447 are thought to lie within predicted binding domains for the transcription factors Pbx-1 and MZF1, respectively. In addition, insertions at position -43 (G), -47 (C), -71 (G) and a C to T substitution at position -198 were found in all DNA samples compared with the published ccn2 (ctgf) promoter sequence. These corrections do not involve sequences predicted to function as transcription factor binding sites. CONCLUSION: Sequence analysis of the ccn2 (ctgf) promoter of 77 human DNA samples has revealed corrections and polymorphic sites. The latter lie within putative regulatory elements.

Enhanced response of psoriasis to UVB therapy after pretreatment with a lubricating base. A single-blind controlled study.

Forty-three out-patients with stable plaque-type psoriasis involving 10-30% of the skin participated in a single-blind controlled study. The psoriasis lesions on one half of the body were treated with a lubricating base of the oil-in-water type before UVB exposure, while those on the other side of the body received UVB only. The rates of improvement of scaling, infiltration and erythema were compared in 127 symmetrical pairs of psoriasis plaques. The scores for the three variables were then summed to yield a total score for the effect of treatment. After only 2 weeks of treatment and throughout the treatment period the rate of improvement in the total score was significantly (p less than 0.001) accelerated on the body half treated with the emollient compared with the control side. Pretreatment with a suitable lubricating base can thus result in shorter treatment periods, which means that the surrounding skin will be exposed to smaller doses of UVB, with a diminished risk of actinic damage.

Long-term oral acyclovir treatment prevents recurrent genital herpes.

Thirty-three patients with frequently recurring genital herpes completed a randomized double-blind, crossover trial with oral acyclovir 200 mg 4 times a day and placebo for periods of 12 weeks. Five patients (15%) had full recurrence during acyclovir treatment and 31 (94%) while receiving placebo. The median time to first recurrence was 20 days for placebo and more than 84 days for acyclovir. It was concluded that acyclovir was well tolerated and an effective treatment to suppress the disease in selected cases of severe and frequently recurring genital herpes. However, the relapses seem to occur with the same rate as before, when the suppressive acyclovir treatment is stopped.

Topical treatment with sulfur 10 per cent for rosacea.

In a controlled study, topical treatment with sulfur 10 per cent is shown to be equally effective as orally given tetracycline in the management of rosacea.

Zinc deficiency with transitory acrodermatitis enteropathica in a boy of low birth weight.

A premature male baby fed on his mother's milk developed zinc deficiency and a skin disorder inseparable from acrodermatitis enteropathica. Following zinc therapy the skin lesions healed. Later the treatment was withheld and no recurrence was seen during 30 months' observation. The boy's zinc deficiency was thought to be due to a high requirement secondary to rapid growth, to poor zinc supply in food and, possibly, to inefficient zinc absorbtion.