Cons��quences r��nales des traitements de l��ob��sit��

Medical or surgical treatments of obesity have demonstrated their efficacy in reducing glomerular hyperfiltration, albuminuria and the risk of chronic kidney disease among obese patients. Hyperprotidic regimens are contraindicated among patients with renal disease because they worsen it. Bypass bariatric surgery increases oxaluria, with a significant risk of renal lithiasis. During treatments of obesity, a multidisciplinary approach including a nephrologist may limit the occurrence of these renal complications.     

Symposium on obesity and asthma �CNovember 2, 2006

Asthma and obesity are frequently associated, and obesity has been considered a factor contributing to both an increase in severity of asthma and to its development. The present document summarizes the proceedings of a symposium held in Montreal, Quebec, on November 2, 2006, under the auspices of the Réseau en santé respiratoire du Fonds de la recherche en santé du Québec in collaboration with the McGill University – Strauss Severe Asthma Program, Université Laval (Quebec City) and Université de Montréal. It includes an overview of the various aspects of the relationships between asthma and obesity with regard to animal models; genetic, hormonal and physiological determinants; influence of comorbidities (eg, sleep apnea syndrome); epidemiology; clinical and psychological features; and management of asthma in the obese population.     

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.     

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??Objective To observe the changes of red cell distribution width ??RDW?? in children with heart failure secondary to dilated cardiomyopathy??DCM????and to explore the correlations between RDW and the common parameters of cardiac function. Methods Totally 68 children with heart failure secondary to DCM were enrolled. According to the modified Ross scoring system??the children were divided into 3 subgroups?? mild??moderate and severe heart failure subgroups. Fifty healthy children were selected as control group. RDW levels were compared among the groups. The correlation analysis was performed between RDW and plasma N-terminal brain natriuretic peptide ??NT-proBNP??as well as left ventricular ejection fraction??LVEF??. Results RDW levels in children with heart failure secondary to DCM were significantly higher than the control group ??P??0.01??.With increasing heart failure grade??NT-proBNP levels were elevated gradually and LVEF were decreased gradually ??both P??0.01????RDW levels had no significant difference among the heart failure groups??P??0.05??. RDM was not correlated with NT-proBNP or LVEF??r??0.144??r??-0.158??P??0.05??. Conclusion In children with DCM??RDW can be used as a new diagnostic marker of heart failure??but it can not reflect the severity of heart failure.     

Impact of laughter on air trapping in severe chronic obstructive lung disease

Static and dynamic hyperinflation is an important factor of exertional dyspnea in patients with severe COPD. This proof-of-concept intervention trial sought to study whether laughter can reduce hyperinflation through repetitive expiratory efforts in patients with severe COPD. For small groups of patients with severe COPD (n = 19) and healthy controls (n = 10) Pello the clown performed a humor intervention triggering regular laughter. Plethysmography was done before and up to 24 hours after intervention. Laughing and smiling were quantified with video-analysis. Real-time breathing pattern was assessed with the LifeShirt™, and the psychological impact of the intervention was monitored with self-administered questionnaires. The intervention led to a reduction of TLC in COPD (p = 0.04), but not in controls (p = 0.9). TLC reduction was due to a decline of the residual volume. Four (22 [CI 95% 7 to 46] %) patients were ≥10% responders. The frequency of smiling and TLC at baseline were independent predictors of TLC response. The humor intervention improved cheerfulness, but not seriousness nor bad mood. In conclusion, smiling induced by a humor intervention was able to reduce hyperinflation in patients with severe COPD. A smiling-derived breathing technique might complement pursed-lips breathing in patients with symptomatic obstruction.     

Structural evolution of the membrane-coating module of the nuclear pore complex

The coatomer module of the nuclear pore complex borders the cylinder-like nuclear pore-membrane domain of the nuclear envelope. In evolution, a single coatomer module increases in size from hetero-heptamer (Saccharomyces cerevisiae) to hetero-octamer (Schizosaccharomyces pombe) to hetero-nonamer (Metazoa). Notably, the heptamer–octamer transition proceeds through the acquisition of the nucleoporin Nup37. How Nup37 contacts the heptamer remained unknown. Using recombinant nucleoporins, we show that Sp-Nup37 specifically binds the Sp-Nup120 member of the hetero-heptamer but does not bind an Sc-Nup120 homolog. To elucidate the Nup37–Nup120 interaction at the atomic level, we carried out crystallographic analyses of Sp-Nup37 alone and in a complex with an N-terminal, ∼110-kDa fragment of Sp-Nup120 comprising residues 1–950. Corroborating structural predictions, we determined that Nup37 folds into a seven-bladed β-propeller. Several disordered surface regions of the Nup37 β-propeller assume structure when bound to Sp-Nup120. The N-terminal domain of Sp-Nup120^1–950 also folds into a seven-bladed propeller with a markedly protruding 6D–7A insert and is followed by a contorted helical domain. Conspicuously, this 6D–7A insert contains an extension of 50 residues which also is highly conserved in Metazoa but is absent in Sc-Nup120. Strikingly, numerous contacts with the Nup37 β-propeller are located on this extension of the 6D–7A insert. Another contact region is situated toward the end of the helical region of Sp-Nup120^1–950. Our findings provide information about the evolution and the assembly of the coatomer module of the nuclear pore complex.     

Radiocarbon dates from the Grotte du Renne and Saint-C��saire support a Neandertal origin for the Chatelperronian

The transition from the Middle Paleolithic (MP) to Upper Paleolithic (UP) is marked by the replacement of late Neandertals by modern humans in Europe between 50,000 and 40,000 y ago. Châtelperronian (CP) artifact assemblages found in central France and northern Spain date to this time period. So far, it is the only such assemblage type that has yielded Neandertal remains directly associated with UP style artifacts. CP assemblages also include body ornaments, otherwise virtually unknown in the Neandertal world. However, it has been argued that instead of the CP being manufactured by Neandertals, site formation processes and layer admixture resulted in the chance association of Neanderthal remains, CP assemblages, and body ornaments. Here, we report a series of accelerator mass spectrometry radiocarbon dates on ultrafiltered bone collagen extracted from 40 well-preserved bone fragments from the late Mousterian, CP, and Protoaurignacian layers at the Grotte du Renne site (at Arcy-sur-Cure, France). Our radiocarbon results are inconsistent with the admixture hypothesis. Further, we report a direct date on the Neandertal CP skeleton from Saint-Césaire (France). This date corroborates the assignment of CP assemblages to the latest Neandertals of western Europe. Importantly, our results establish that the production of body ornaments in the CP postdates the arrival of modern humans in neighboring regions of Europe. This new behavior could therefore have been the result of cultural diffusion from modern to Neandertal groups.     

Anti-CD20 IgA can protect mice against lymphoma development: evaluation of the direct impact of IgA and cytotoxic effector recruitment on CD20 target cells

Background

While most antibody-based therapies use IgG because of their well-known biological properties, some functional limitations of these antibodies call for the development of derivatives with other therapeutic functions. Although less abundant than IgG in serum, IgA is the most abundantly produced Ig class in humans. Besides the specific targeting of its dimeric form to mucosal areas, IgA was shown to recruit polymorphonuclear neutrophils against certain targets more efficiently than does IgG1.

Design and Methods

In this study, we investigated the various pathways by which anti-tumor effects can be mediated by anti-CD20 IgA against lymphoma cells.

Results

We found that polymeric human IgA was significantly more effective than human IgG1 in mediating direct killing or growth inhibition of target cells in the absence of complement. We also demonstrated that this direct killing was able to indirectly induce the classical pathway of the complement cascade although to a lesser extent than direct recruitment of complement by IgG. Recruitment of the alternative complement pathway by specific IgA was also observed. In addition to activating complement for lysis of lymphoma cell lines or primary cells from patients with lymphoma, we showed that monomeric anti-CD20 IgA can effectively protect mice against tumor development in a passive immunization strategy and we demonstrated that this protective effect may be enhanced in mice expressing the human FcαRI receptor on their neutrophils.

Conclusions

We show that anti-CD20 IgA antibodies have original therapeutic properties against lymphoma cells, with strong direct effects, ability to recruit neutrophils for cell cytotoxicity and even recruitment of complement, although largely through an indirect way.Key words: Anti-CD20 IgA, lymphoma, FcαRI     

Early Failure Secondary to Noncoronary Leaflet Prolapse in a Stentless Aortic Bioprosthesis

Structural degeneration is an important long-term disadvantage of biologic prostheses. However, early failure of these prostheses is uncommon and is usually caused by rapid calcification. We report the successful management of a rare case of early failure of a stentless aortic bioprosthesis (within 4 months of implantation). The patient presented with severe noncalcific aortic regurgitation secondary to prolapse of the noncoronary leaflet. In consideration of the acute nature of failure in this new-generation bioprosthesis and its unclear cause, we believe that this report, albeit of a single case, warrants some attention.Key words: Aortic valve insufficiency/surgery, bioprosthesis/failure, complication, disease progression, heart valve prosthesis/failure, reoperationAortic valve replacement using stentless biological prostheses offers the benefits of good hemodynamics,¹ without the requirement of prolonged anticoagulation.² Although their major drawback—structural degeneration in the long term—is well documented,³ bioprostheses rarely fail early, and, when they do, rapid calcification of the valve leaflets is the usual cause.⁴ We report the successful management of a rare case of early failure of a stentless aortic bioprosthesis within 4 months of implantation. The patient presented with severe noncalcific aortic regurgitation secondary to prolapse of the noncoronary leaflet.