Melatonin rhythm and other outputs of the master circadian clock in the desert goat (Capra hircus) are entrained by daily cycles of ambient temperature

In desert areas, mammals such as camel and goat are exposed to harsh environmental conditions. The ambient temperature (Ta) cycles have been shown to entrain the circadian clock in the camel. In the present work, we assumed that, in the goat living in a desert biotope, Ta cycles would have the same synchronizing effect on the central clock. Therefore, the effects of Ta cycles on body temperature (Tb), locomotor activity (LA) and melatonin (Mel) rhythms as outputs of the master circadian clock have been studied. The study was performed on bucks kept first under constant conditions of total darkness (DD) and constant Ta, then maintained under DD conditions but exposed to Ta cycles with heat period during subjective day and cold period during subjective night. Finally, the Ta cycles were reversed with highest temperatures during the subjective night and the lowest temperatures during the subjective day. Under constant conditions, the circadian rhythms of Tb and LA were free running with an endogenous period of 25.3 and 25.0 hours, respectively. Ta cycles entrained the rhythms of Tb and LA to a period of exactly 24.0 hours; while when reversed, the Ta cycles led to an inversion of Tb and LA rhythms. Similarly, Ta cycles were also able to entrain Mel rhythm, by adjusting its secretion to the cooling phase before and after Ta cycles inversion. All together, these results show that the Ta cycles entrain the master circadian clock in the goat.     

Le lepréchaunisme : diagnostic prénatal et prise en charge

Leprechaunism or Donohue syndrome is a very rare malformation (less than one case per million), caused by a genetic insulin resistance. We report a case of a patient whose diagnosis was made at birth in gynecology-obstetrics “C” University Hospital Ibn Rushd Casablanca. The case arose as a result of a consanguineous marriage. Donohue syndrome is an autosomal recessive disease corresponding to a severe congenital form of extreme insulin resistance syndrome. The total resistance to insulin makes his prognosis always pejorative. Early prenatal diagnosis is possible, leaving the possibility for parents to request a termination of pregnancy for medical reasons.     

Episodic memory and executive function impairments in non-demented older adults: which are the respective and combined effects on gait performances?

Gait control depends in part on cognition. This study aims to examine the separate and combined effects of episodic memory and executive function impairments on the mean value and the coefficient of variation (CoV) of stride time among non-demented older community dwellers. Based on a cross-sectional design, 1458 older community dwellers without dementia (70.6 ± 4.9 years; 49.2 % female) were recruited and separated into cognitively healthy individuals (CHI) and individuals with cognitive impairment. A score ≤5/6 on the Short Mini-Mental State Examination defined episodic memory impairment. Impaired executive function was defined by errors on the clock-drawing test. Mean value and CoV of stride time were measured by the GAITRite® system. A total of 517 participants (35.5 %) had cognitive impairment in at least one cognitive domain. Participants with memory impairment (P = 0.006) and those with combined cognitive impairments (P < 0.001) had greater (i.e., worse gait performance) mean value of stride time (P = 0.006) compared to CHI. Participants with combined cognitive impairment had a greater CoV of stride time (i.e., worse gait performance) compared to CHI (P = 0.004) and to those with separate memory impairment (P = 0.037). Among participants with combined cognitive impairments, mean value and CoV of stride time had the highest effect size (respectively, effect size = 0.49 [95 % confidence interval (CI) 0.27;0.71] and effect size = 0.40 [95 %CI 0.18;0.62]). Participants with episodic memory or executive impairments had a greater mean value and CoV of stride time compared to those with no cognitive impairment. Combined episodic memory and executive impairments exceeded the sum of separate impairments on gait performances, suggesting a complex interplay going beyond a simple additive effect.     

Management of iron overload in hemoglobinopathies

Hemoglobinopathies, thalassemia and sickle cell disease are among the most frequent monogenic diseases in the world. Transfusion has improved dramatically their prognosis, but provokes iron overload, which induces multiple organ damages. Iron overload is related to accumulation of iron released from hemolysis and transfused red cell, but also, in thalassemic patients, secondary to ineffective erythropoiesis, which increases intestinal iron absorption via decreased hepcidin production. Transfusion-related cardiac iron overload remains a main cause of death in thalassemia in well-resourced countries, and is responsible for severe hepatic damages in sickle cell disease. Regular monitoring by Magnetic Resonance Imaging (MRI) using myocardial T2* (ms) and Liver Iron Content (LIC) (mg of iron/g dry weight) are now standards of care in chronically transfused patients. Serum ferritin level measurements and record of the total number of transfused erythrocyte concentrates are also helpful tools. Three iron chelators are currently available, deferoxamine, which must be injected subcutaneously or intravenously, and two oral chelators, deferiprone and deferasirox. We will review the main characteristics of these drugs and their indications.     

Human bone morphogenetic protein‐7 does not counteract aristolochic acid‐induced renal toxicity

Aristolochic acids (AA) are nephrotoxic and profibrotic agents, leading to chronic kidney disease. As some controversial studies have reported a nephroprotective effect of exogenous recombinant human bone morphogenetic protein (rhBMP)‐7 in several models of renal fibrosis, we investigated the putative effect of rhBMP‐7 to prevent progressive tubulointerstitial damage after AA intoxication in vitro and in vivo. In vitro, the toxicity of AA on renal tubular cells was demonstrated by an increase in vimentin as well as a decrease in β‐catenin expressions, reflecting a dedifferentiation process. Increased fibronectin and interleukin‐6 levels were measured in the supernatants. Enhanced α‐SMA mRNA levels associated to decreased E‐cadherin mRNA levels were also measured. Incubation with rhBMP‐7 only prevented the increase in vimentin and the decrease in β‐catenin expressions. In vivo, in a rat model of AA nephropathy, severe tubulointerstitial lesions induced by AA after 10 and 35 days (collagen IV deposition and tubular atrophy), were not prevented by the rhBMP‐7 treatment. Similarly, rhBMP‐7 did not ameliorate the significant increase in urinary concentrations of transforming growth factor‐β. In summary, our in vitro data demonstrated a poor beneficial effect of rhBMP‐7 to reverse cell toxicity while, in vivo, there was no beneficial effect of rhBMP‐7. Therefore, further investigations are needed to confirm the exact role of BMP‐7 in progressive chronic kidney disease. Copyright © 2015 John Wiley & Sons, Ltd.