Increased body iron stores in elite road cyclists

BACKGROUND: One third of French elite road cyclists were found to have hyperferritinemia on antidoping control tests performed during the Tour de France in 1998. PURPOSE: This study was undertaken to determine whether hyperferritinemia corresponded to elevated body iron stores or not and, affirmatively, what were its mechanism, its clinical consequences, and its spontaneous course. METHODS: 83 elite road male cyclists presenting with hyperferritinemia, defined as serum ferritin level greater than 300 microg.L-1, were studied with respect to consumption of iron and other drugs, serum iron tests, HFE mutations, and hepatic iron concentration (HIC; N < 35 micromol.g-1 dry weight). RESULTS: All cyclists were asymptomatic and had normal physical and cardiac examination. Their median (range) serum ferritin, serum iron, and transferrin saturation levels were 504 microg.L-1 (306-1671), 20 micromol.L-1 (8.5-36.3), and 39% (20-76), respectively. HIC was increased in 24/27 up to 187 micromol.g-1. Allelic frequency of the H63D mutation was increased in cyclists when compared to controls (P = 0.04). However, iron tests did not differ according to HFE genotypes. Most cyclists (89%) had been supplemented with iron. The median iron supplementation was 25.5 g (range: 1.4-336) and correlated well (P = 0.002) with serum ferritin. Evolution of serum ferritin levels did not differ whether cyclists had been continuing iron supplementation or not. CONCLUSION: Hyperferritinemia in elite road cyclists accounted for increased body iron stores caused by and persisting after cessation of excessive iron supplementation. Even when mild, iron excess may expose to long-term complications and should be removed, at least at the time when professional cyclists retire. To prevent iatrogenic iron overload, supplementation with iron must be done according to serum ferritin follow-up and not either blindly or on the basis of serum iron determination only.     

HIV-1 subtypes and recombinants in the Republic of Congo.

To document the actual genetic diversity of HIV-1 strains in the Republic of Congo, 114 HIV-1 positives persons were sampled in 2003 and 2004 after their informed consent. They were attending the teaching hospital, the reference health center in Makelekele, Brazzaville and the regional hospital centers in Pointe-Noire, Gamboma and Ouesso. A total of 104 samples were genetically characterized by direct sequencing of the p24 gag region and 80 were also subtyped in the V3-V5 env region. The genetic subtype distribution of the Congolese strains showed the predominance of subtype A (36.5% and 32.5% in gag and env, respectively) and G (30.8% and 21.25%), whereas subtype D strains represented 12.5% and 15%. Subtypes C, F, H, J, K and the CRFs-01, -02, -05 -06, and also the recently characterized CRF18 were seen at lower rates. Finally, 4.8% (gag) and 6.25% (env) of the strains could not be classified. Moreover, a high intra-subtype diversity was observed in our study. Among 70 strains which have been characterized in the two genomic regions, 14 (20%) appeared to be unique recombinants. These data show a high genetic variability in the Republic of Congo, where all the subtypes have been documented together with certain subsubtypes and several CRFs.     

Effects of diclofenac on experimental streptococcal necrotizing fasciitis (NF) in rabbit

Abstract Aggravation of necrotizing fasciitis (NF) by the administration of non-steroidal antiinflammatory drugs (NSAIDs) has recently been suggested. A rabbit model of streptococcal NF was used to study the effects of parenteral administration of an NSAID on NF evolution and outcome. Of 16 rabbits inoculated with a Streptococcus pyogenes suspension together with staphylococcal alpha toxin, 8 were treated with two doses of 4 mg/kg diclofenac on day 1 after inoculation. Clinical, bacteriological and histological studies were performed until day 10. Under our experimental conditions, NSAID treatment significantly limited NF extension. A specific inverse relationship between the extent of inflammation and bacterial density in NF lesions was observed on day 1 after inoculation in the treated group suggesting that the greater severity of NF in humans treated with an NSAID could be due to the therapeutic delay induced by the misleading clinical effects of the NSAID, and not to inhibition of antibacterial defence. Received: 23 October 1997 / Received after revision: 23 June 1998 / Accepted: 30 July 1998     

Arteriosclerosis, vascular calcifications and cardiovascular disease in uremia

PURPOSE OF REVIEW: Arterial calcification in chronic kidney disease (CKD) is associated with increased cardiovascular risk. The mechanisms responsible for arterial calcification include alterations of mineral metabolism and expression of mineral-regulating proteins. RECENT FINDINGS: Arterial calcification is similar to bone formation, involving differentiation of vascular smooth muscle cells (VSMCs) into phenotypically distinct osteoblast-like cells. Elevated phosphate and/or calcium trigger a concentration-dependent increase of calcium precipitates in VSMC in vitro. The calcification is initiated by VSMC release of membrane-bound matrix vesicles and formation of apoptotic bodies. The presence of serum prevents these changes, indicating the presence of calcification inhibitors. Arterial calcification occurs in two sites: the tunica intima and tunica media. Intimal calcification is a marker of atherosclerotic disease and is associated with arterial stenotic lesions. Medial calcification influences outcome by promoting arterial stiffening whose principal consequences are left-ventricular hypertrophy and altered coronary perfusion. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in CKD patients. Age, duration of dialysis, smoking and diabetes are risk factors for the development of arterial calcification in end-stage renal disease. Oversuppression of parathyroid hormone and low bone turnover potentiate the development of arterial calcification. SUMMARY: Arterial disease in CKD patients is characterized by extensive calcification. Evidence has accumulated pointing to the active and regulated nature of the calcification process. Elevated phosphate and calcium may stimulate sodium-dependent phosphate cotransport involving osteoblast-like changes in cellular gene expression. Arterial calcification is responsible for stiffening of the arteries with increased left-ventricular afterload and abnormal coronary perfusion as the principal clinical consequences.     

Starting Block Performance in Sprinters: A Statistical Method for Identifying Discriminative Parameters of the Performance and an Analysis of the Effect of Providing Feedback over a 6-Week Period

The purpose of this study was twofold: (a) to examine if kinetic and kinematic parameters of the sprint start could differentiate elite from sub-elite sprinters and, (b) to investigate whether providing feedback (FB) about selected parameters could improve starting block performance of intermediate sprinters over a 6-week training period. Twelve male sprinters, assigned to an elite or a sub-elite group, participated in Experiment 1. Eight intermediate sprinters participated in Experiment 2. All athletes were required to perform three sprint starts at maximum intensity followed by a 10-m run. To detect differences between elite and sub-elite groups, comparisons were made using t-tests for independent samples. Parameters reaching a significant group difference were retained for the linear discriminant analysis (LDA). The LDA yielded four discriminative kinetic parameters. Feedback about these selected parameters was given to sprinters in Experiment 2. For this experiment, data acquisition was divided into three periods. The first six sessions were without specific FB, whereas the following six sessions were enriched by kinetic FB. Finally, athletes underwent a retention session (without FB) 4 weeks after the twelfth session. Even though differences were found in the time to front peak force, the time to rear peak force, and the front peak force in the retention session, the results of the present study showed that providing FB about selected kinetic parameters differentiating elite from sub-elite sprinters did not improve the starting block performance of intermediate sprinters.

Key Points

• The linear discriminative analysis allows the identification of starting block parameters differentiating elite from sub-elite athletes.
• 6-week of feedback does not alter starting block performance in training context.
• The present results failed to confirm previous studies since feedback did not improve targeted kinetic parameters of the complex motor task in real-world context.

Key words: Feedback, kinetic, kinematic, performance, sprint     

Therapeutic failure of cinacalcet in a renal transplant patient presenting hyperparathyroidism with severe hypercalcaemia

Sir, In our experience, 10% of renal allograft recipients developsustained hyperparathyroidism and hypercalcaemia during thefirst year following renal transplantation. Persistent hypercalcaemiausually requires parathyroidectomy, which represents the onlydefinitive treatment currently available. Cinacalcet, a calcimimeticdrug, represents from now on an alternative     

A new potential cyclooxygenase-2 inhibitor, pyridinic analogue of nimesulide

In this paper, the binding mode of original pyridinic compounds structurally related to nimesulide, a preferential cyclooxygenase (COX)-2 inhibitor, is analyzed by docking simulations in order to understand structure-activity relationships of this family. Structural modifications are proposed to reverse the selectivity of the more active inhibitor of the series characterized by a preferential activity on COX-1. On the basis of these modifications, a new compound with a bromo substituent was designed and showed a COX-2 selective inhibition.     

Effect of mutating the two cysteines required for HBe antigenicity on hepatitis B virus DNA replication and virion secretion

Hepatitis B virus (HBV) variants with impaired expression of e antigen (HBeAg) frequently arise at the chronic stage of infection, as exemplified by precore and core promoter mutants. Since an intramolecular disulfide bond maintains the secondary structure of HBeAg, we explored effect of missense mutations of either cysteine codon. Consistent with earlier reports, substitution of each cysteine rendered HBeAg nearly undetectable. With underlying nucleotide changes at the loop of pregenome encapsidation signal, the C-7 mutants were severely impaired in pregenomic RNA packaging and hence DNA replication. Although none of the missense mutations at C61 reduced DNA replication, replacement with arginine, but not alanine, aspartic acid, phenylalanine, or serine, blocked virion secretion. Consistent with the detection of C61R genome from a patient serum, secretion block of the C61R mutant could be overcome by co-expression of wild-type core protein. In conclusion, point mutations of the C61 codon may generate viable HBeAg-negative variants.     

Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes

Doublecortin (DCX) is a microtubule-associated protein involved in neuronal migration, which causes X-linked lissencephaly and subcortical laminar heterotopia (SCLH) when mutated. Here we show that DCX interacts with the ubiquitin-specific protease Drosophila fat facets related on X chromosome (DFFRX). This interaction was confirmed by targeted mutagenesis, colocalization, and immunoprecipitation studies. DFFRX is thought to deubiquitinate specific substrates including beta-catenin, preventing their degradation by the proteasome. Interestingly, unlike beta-catenin, no ubiquitinated forms of DCX could be detected, and indeed we show that DCX interacts with a novel recognition domain in DFFRX, located outside of its catalytic site. We also show that DFFRX associates with microtubules at specific subcellular compartments, including those enriched in DCX. These results thus suggest that in addition to vesicular trafficking, DCX may play a role in the regulation of cell adhesion via its interaction with DFFRX in migrating and differentiating neurons.