Metabolic evidence for adaptation to a high protein diet in rats

This study was designed to assess the effects of long-term adaptation to a high protein diet on energy intake, body weight gain, body composition and splanchnic metabolic indicators in rats. For this purpose, adult male Wistar rats were fed either a 50 g/100 g dry matter (DM) protein diet (P50 group) or a 14 g/100 g DM protein diet (P14 group) for 21 d. These two groups were compared with a P14 pair-fed (P14-pf) group that consumed the same daily energy as the P50 group. The energy intake of the P50 group was 16 +/- 1% less than that of the P14 group (P < 0.05), and the P50 group had significantly lower body weight. The P50 group had significantly less adipose tissue compared with both P14 and P14-pf rats. The activities of the brush border membrane enzymes, neutral aminopeptidase and gamma-glutamyl transferase, were significantly higher in the P50 group than in the P14 rats. Similarly, the activities of alanine aminotransferase, arginase and serine dehydratase were significantly higher in the liver of P50 rats compared with P14 rats. Both amino acid transporter system A and X(A,G-) activities, measured in freshly isolated hepatocytes, were significantly higher in the P50 group (8- and 1.5-fold, P < 0.05, respectively) compared with the P14 group. The 1.5-fold increase in the steady-state activity of X(A,G-) was accompanied by a doubling of EAAT2 mRNA, involved in the system X(A,G-). This study provides confirmation that specific biochemical and molecular adaptive processes of the splanchnic area are involved in the response to variations in the protein content of the diet.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.     

Predicting Hip Fracture Type With Cortical Bone Mapping (CBM) in the Osteoporotic Fractures in Men (MrOS) Study

Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual‐energy X‐ray (DXA)‐based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have subdivided fracture into types, because this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The Osteoporotic Fractures in Men (MrOS) study is a predictive case‐cohort study of men over 65 years old: we analyze 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5994. To our knowledge, this is the largest QCT‐based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We show that both cortical mass surface density and endocortical trabecular BMD are significantly different in fracture cases versus cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA‐based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave‐one‐out cross‐validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 for trochanteric fractures and 0.76 to 0.82 for femoral neck fractures. In contrast, adding DXA‐based BMD to a CBM‐based predictive model does not result in any significant improvement. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.     

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.      

Prevalence of Deficient Retro-Aortic Rim and Its Effects on Outcomes in Device Closure of Atrial Septal Defects

Deficient retro-aortic rim is of concern as a risk factor for aortic erosion after device closure of atrial septal defects (ASD). However, its prevalence and contribution to technical failure and adverse outcomes have not been delineated. A single-center retrospective cohort study of children and adults undergoing cardiac catheterization for device occlusion of ASD from 1 January 1999 to 1 April 2012 was performed. Risk factors for technical failure and early adverse outcome were assessed using multivariate logistic regression. During the study period, 445 consecutive subjects with a median age of 5.9 years (range, 0.8–80 years) underwent catheterization. Of the subjects with reviewable echocardiograms, 60 % had deficient retro-aortic rim. No attempt at device closure was made for 3.6 % of the subjects. Of the remaining 429 subjects, 96 % underwent successful device occlusion. Major early adverse events occurred in 1.2 % (95 % confidence interval 0.4–2.7 %) of the cases, all of them either device embolization or malposition. Deficient retro-aortic rim was not a risk factor for composite outcome of technical failure or early major adverse event. No deaths, late reinterventions, or erosion events occurred during 2,395 total person-years (median, 5.8 years) of follow-up evaluation. Deficient retro-aortic rim was associated with increased risk of device impingement on the aorta, but no association was seen between device impingement or deficient retro-aortic rim and the development of new/progressive aortic insufficiency. Deficient retro-aortic rim is highly prevalent but did not increase the risk of adverse outcomes. Its contribution to the risk of aortic erosion could not be addressed by this study.