Ferroportin Q248H mutation,hyperferritinemia and atypical type 2 diabetes mellitus in South Kivu

BackgroundThe ferroportin Q248H mutation is relatively common in sub-Saharan Africa. No previous study examined its relationship with atypical diabetes mellitus (DM) in this area.ObjectiveTo determine the potential interactions between ferroportin Q248H mutation, hyperferritinemia and DM in South Kivu (RDC).MethodologyPresence of ferroportin Q248H mutation and iron status were investigated in diabetic patients (n = 179, age (mean) 57.7 years, CRP (median) 0.16 mg/L) and non-diabetic subjects (n = 86, age 44.5 years, CRP 0.07 mg/L) living in the city of Bukavu. Hyperferritinemia was considered for values greater than 200 and 300 μg/L in women and in men, respectively.ResultsThe prevalence of ferroportin Q248H mutation [12.1%] was non-significantly higher in diabetics than non-diabetics [14.0% vs. 8.1%, p = 0.17]. Similarly, hyperferritinemia frequency was higher in diabetic patients with Q248H mutation [44.0% vs. 14.3%, p = 0.16] and in mutation carriers [37.0% vs 16.5%, p = 0.001] than in the control groups, respectively. The association between Q248H mutation and DM was nevertheless not significant [adjusted OR 1.70 (95% CI: 0.52–5.58), p = 0.37], whereas hyperferritinemia [OR 2.72 (1.24–5.98), p = 0.01] showed an independent effect after adjustment for age and metabolic syndrome.ConclusionsThe present work suggests a potential association between abnormal iron metabolism, ferroportin Q248H mutation and atypical DM in Africans, which may be modulated by environmental factors.     

Neuroendocrine control of a sexually dimorphic behavior by a few neurons of the pars intercerebralis in Drosophila

In Drosophila, locomotor activity is sexually dimorphic and the brain area controlling this dimorphism has been mapped. The neurons of the pars intercerebralis (PI) have been suggested to participate in such differences between males and females. However, the precise physical nature of the dimorphism, the identity of the PI neurons involved, and the nature of the neuronal signal coding the dimorphism remain unknown. In this study, we used a video-tracking paradigm to characterize further the pattern of locomotor activity in Drosophila. We show that the number of activity/inactivity periods (start/stop bouts) is also sexually dimorphic, and that it can be genetically feminized in males. Moreover, the transplantation of PI neurons from a female, or of feminized PI neurons from a donor male into a receiver wild-type male is sufficient to induce the feminization of locomotor behavior, confirming that this tiny cluster of approximately 10 neurons is directly responsible for the sexual dimorphism in locomotor activity. Finally, feeding males with fluvastatin, a juvenile hormone (JH) inhibitor, also led to start/stop feminization, and this effect is reversible by the simultaneous application of methoprene, a JH analog, suggesting the existence of a neuroendocrine control, by JH, of such behavioral dimorphism.     

Quantification of cumulated physical fatigue at the workplace

Quantification of physical fatigue remains a challenge. We hypothesized that its effects on central autonomic nervous system activity could be explored for such a quantification. To test this relationship, we prospectively measured central autonomic nervous activity through nocturnal heart rate variability (HRV) in six French garbage collectors, aged 32.1+/-4.3 years, twice a week during 3 consecutive weeks of work, and during the following week of rest. Eight healthy sedentary males formed a control group. HRV indices were calculated by applying standard temporal domain and wavelet transform analyses to standard ECG recordings. During the 3 consecutive weeks of work, there was a significantly progressive decrease in HRV indices, particularly pNN50 (-34.2%, P<0.05), as well as the high (-33.3%, P<0.05) and low (-22.2%, P<0.01) frequency components of wavelet transform, while there was an increase, although non-significant, of the ratio of low to high frequencies (9.1%). During the resting period, there was a significant recovery of HRV indices, notably of its high (50.0%, P<0.05) and low (28.6%, P<0.05) frequency components. No such changes occurred in the control group. A central signature of cumulated physical fatigue can thus be detected and quantified through nocturnal autonomic nervous system activity. Its characteristics are those of a progressive parasympathetic withdrawal.     

Simple repair of aortico-left ventricular tunnel in a newborn with early prenatal diagnosis

We report a case with very early antenatal diagnosis of aortico-left ventricular tunnel (ALVT) at 22 weeks of pregnancy. Early recognition of ALVT by antenatal ultrasound allows prompt neonatal management and avoidance of harmful aortic valve regurgitation. The present case is unique because of the conjunction of very early antenatal diagnosis, prompt postnatal management, early surgical repair on the sixth day of life, direct closure from the aorta of the aortic orifice only, and optimal postoperative course with excellent mid-term result.     

Novel role for STAT3 in transcriptional regulation of NK immune cell targeting receptor MICA on cancer cells

The role of natural killer group 2, member D receptor (NKG2D)-expressing natural killer (NK) cells in tumor immunosurveillance is now well established. Nevertheless, tumor progression occurs despite tumor immunosurveillance, leading to cancer persistence in immunocompetent hosts. STAT3 plays a pivotal role both in oncogenic functions and in immunosuppression. In this study, we investigated the role of STAT3 in suppressing NK cell-mediated immunosurveillance. Using a colorectal cancer cell line (HT29) that can poorly activate NK, we neutralized STAT3 with pharmacologic inhibitors or siRNA and found that this led to an increase in NK degranulation and IFN-γ production in a TGF-β1-independent manner. Exposure to NKG2D-neutralizing antibodies partially restored STAT3 activity, suggesting that it prevented NKG2D-mediated NK cell activation. On this basis, we investigated the expression of NKG2D ligands after STAT3 activation in HT29, mesenchymal stem cells, and activated lymphocytes. The NK cell recognition receptor MHC class I chain-related protein A (MICA) was upregulated following STAT3 neutralization, and a direct interaction between STAT3 and the MICA promoter was identified. Because cross-talk between DNA damage repair and NKG2D ligand expression has been shown, we assessed the influence of STAT3 on MICA expression under conditions of genotoxic stress. We found that STAT3 negatively regulated MICA expression after irradiation or heat shock, including in lymphocytes activated by CD3/CD28 ligation. Together, our findings reveal a novel role for STAT3 in NK cell immunosurveillance by modulating the MICA expression in cancer cells.     

The effects of parathyroid hormone fragments on bone formation and their lack of effects on the initiation of colon carcinogenesis in rats as indicated by preneoplastic aberrant crypt formation

The parathyroid hormone (PTH) and some of its fragments and analogs stimulate bone growth in various animal models and humans and one of them (hPTH-(1–34)) has been approved by the USFDA for treating osteoporosis. However, there are reports that PTH can stimulate the PI-3 kinase/mitogen-activated protein kinases-mediated proliferation of rat enterocytes and that primary hyperparathyroidism in humans is associated with an increased incidence of colon cancer. Here we have investigated the ability of two PTH fragments, hPTH-(1–34)NH₂ and [Leu²⁷]cyclo(Glu²²-Lys²⁶)hPTH-(1–31)NH₂ to initiate colon carcinogenesis or increase the initiatory activity of the widely used colon carcinogen azoxymethane (AOM). The initiation of colon carcinogenesis by AOM was indicated by the very early appearance of aberrant crypt foci. While both PTH peptides strongly stimulated femoral bone formation, they did not cause the appearance of ACFs or affect the number or the distribution along the colon of AOM-induced ACFs. Nor did AOM affect the PTHs’ ability to stimulate bone formation. Thus, a relatively short PTH treatment that is long enough to strongly stimulate bone formation does not initiate colon carcinogenesis in rats.     

Habitual physical activity and peak anaerobic power in elderly women

The aim of this study was to investigate the relationship between maximal anaerobic power (P _max) and corresponding optimal velocity (V _opt) and habitual physical activity (PA) on the one hand and with maximal oxygen consumption (V˙O_2max) on the other hand, in elderly women. Twenty-nine community dwelling, healthy women aged 66–82 years participated in the study. PA was evaluated using the Questionnaire d'Activite Physique Saint-Etienne (QAPSE) and expressed using two QAPSE activity indices: mean habitual daily energy expenditure (MHDEE) and daily energy expenditure corresponding to leisure time sports activities (sports activity). The subjects' P _max and V _opt were measured while they cycled on a friction-loaded non-isokinetic cycle ergometer. P _max was expressed relative to body mass [P _max/kg(W?·?kg^?1)], and relative to the mass of two quadriceps muscles [P _{max /Quadr}(W·kg_Quadr ^?1)]. A negative relationship between P _max/kg (Spearman's r?=??0.56; P?P _max/Quadr (r?=??0.53; P?V _opt (r?=??0.45; P?P _max/kg was positively associated with MHDEE (r?=?0.51; P?r?=?0.58; P? P _max/Quadr and V _opt (r?=?0.55; P?r?=?0.54; P?P _max/kg, P _max/Quadr and V _opt correlated positively with V˙O_2max. The positive relationship between ergometer measurements and PA indices was similar to that between V˙O_2max and PA. P _max/kg was, moreover, closely related to V _opt (r?=?0.77; P?P _max/kg variance, whereas sports activity contributed to P _max/Quadr and V _opt variances. In conclusion, the data from this cross-sectional study suggest that in healthy elderly women habitual PA, and especially leisure time PA, alleviates the decline of the P _max of the quadriceps muscles.     

S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship.

We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualité Sociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.     

Chronic Contamination of Rats with <Superscript>137</Superscript>Cesium Radionuclide: Impact on the Cardiovascular System

Cardiovascular system impairment has been observed in children and in liquidators exposed to the Chernobyl nuclear power plant accident. No experimental studies of animals have analyzed whether these disorders might be attributed to chronic ingestion of low levels of cesium 137 (¹³⁷Cs). Biochemical, physiological, and molecular markers of the cardiovascular system were analyzed in rats exposed through drinking water to ¹³⁷Cs at a dose of 500 Bq kg⁻¹ (6500 Bq l⁻¹). Plasma concentrations of CK and CK-MB were higher (+52%, P < 0.05) in contaminated rats. No histological alteration of the heart was observed, but gene expression was modified in the atria. Specifically, levels of ACE (angiotensin converting enzyme) and BNP (brain natriuretic peptide) gene expression increased significantly (P < 0.05). ECG analysis did not disclose any arrhythmia except ST- and RT-segment shortening (−9% and −11%, respectively, P < 0.05) in rats exposed to ¹³⁷Cs. Mean blood pressure decreased (−10%, P < 0.05), and its circadian rhythm disappeared. Overall, chronic contamination by an extreme environmental dose of ¹³⁷Cs for 3 months did not result in cardiac morphological changes, but the cardiovascular system impairments we observed could develop into more significant changes in sensitive animals or after longer contamination. Yann Guéguen and Philippe Lestaevel participated equally to this work.