[Initiation of first dialysis and three months quality of life of patients with end stage renal disease in the French territories of Guadeloupe and Guyane]. / Contexte initial de prise en charge et qualité de vie à 3 mois des patients dialysés pour insuffisance rénale chronique terminale dans deux départements français d'Amérique.

End stage renal disease is a major public health problem in the French Departments of Guadeloupe and Guiana because of the high prevalence of both type 2 diabetes and hypertension. We investigated factors associated with an emergency start of dialysis, 3 months' quality of life for patients starting a first replacement therapy in Guadeloupe and French Guiana using the data of the Réseau épidémiologie et information en néphrologie network, completed with data from the quality of life questionnaires SF-36 and KDQoL. A total of 242 patients (184 in Guadeloupe and 58 in Guiana) were included. An emergency start was found for 112 (46.5%) patients (Guiana: 74.1%; Guadeloupe: 37.7%). In the multivariate model, an emergency start was associated with the number of nephrology consultations in the year before dialysis and the creation of an arteriovenous fistula prior to the first dialysis. The quality of life scores did not differ between the groups emergency start or not but were higher than those measured in mainland French studies on dialyzed population. Lack of nephrology consultations and dialysis preparation are the main factors associated with an emergency start of the first dialysis, highlighting the need to adapt the provision of care for chronic kidney disease in these departments.

[High prevalence of proteinuric nephropathy screened in patients with type 2 diabetes consulting community-based general practitioners in French overseas departments and territories. ALBUM study]. / Prévalence elevée de la protéinurie dépistée en médecine générale chez les patients diabétiques de type 2 dans les DOM-TOM. Etude ALBUM.

UNLABELLED: OBJECTIVE, METHOD: Chronic kidney disease is a major public health problem. This observational epidemiological study aimed to evaluate the prevalence of proteinuric nephropathy in patients with type 2 diabetes consulting a community-based general practitioner in French overseas departments and territories (DOM-TOM). Screening was carried out with reagent strips Albustix for proteinuria and, in case of trace amounts or a negative result, Microalbustix for microalbuminuria. RESULTS: 91 general practitioners participated in the study with 402 evaluable patients (54% female, mean age 60.1 +/- 11.2 years). The duration of diabetes was 8.9 +/- 6.6 years and mean HbA1c was 7.3 +/- 1.4% (52.2% with HbA1c < or = 7%). Screening was positive for 45.7% of the patients: 23.6% positive for proteinuria with Albustix [95% CI: 19.5-27.8] and 22.1% with Microalbustix. CONCLUSION: Screening with reagent strips revealed that nearly half the patients had proteinuria or albuminuria, thus confirming the high prevalence of nephropathy in type 2 diabetes patients living in the Dom-Tom and illustrating the need for frequent renal function screening in type 2 diabetics in general medicine for the prevention of chronic kidney disease.

Dual factor pulse pressure: body mass index and outcome in type 2 diabetic subjects on maintenance hemodialysis. A longitudinal study 2003-2006.

BACKGROUND: Inverse associations between risk factors and mortality have been reported in epidemiological studies of patients on maintenance hemodialysis (MHD). OBJECTIVE: The aim of this prospective study was to estimate the effect of the dual variable pulse pressure (PP) - body mass index (BMI) on cardiovascular (CV) events and death in type 2 diabetic (T2D) subjects on MHD in a Caribbean population. METHODS: Eighty Afro-Caribbean T2D patients on MHD were studied prospectively from 2003 to 2006. Proportional-hazard modeling was used. RESULTS: Of all, 23.8% had a high PP (PP > or = 75th percentile), 76.3% had BMI < 30 Kg/m(2), 21.3% had the dual factor high PP - absence of obesity. During the study period, 23 patients died and 13 CV events occurred. In the presence of the dual variable and after adjustment for age, gender, duration of MHD, and pre-existing CV complications, the adjusted hazard ratio (HR) (95% CI) of CV events and death were respectively 2.7 (0.8-8.3); P = 0.09 and 2.4 (1.1-5.9); P = 0.04. CONCLUSIONS: The dual factor, high PP - absence of obesity, is a prognosis factor of outcome. In type 2 diabetics on MHD, a specific management strategy should be proposed in nonobese subjects with wide pulse pressure in order to decrease or prevent the incidence of fatal and nonfatal events.

High pulse pressure associated with cardiovascular events in patients with type 2 diabetes undergoing hemodialysis.

BACKGROUND: The aims of this study were to examine systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) in patients with type 2 diabetes undergoing hemodialysis (HD), and to assess the relationships between these parameters and cardiovascular (CV) events such as coronary heart disease and congestive cardiac failure. METHODS: A total of 80 Afro-Caribbean type 2 diabetic patients undergoing hemodialysis in three centers in Guadeloupe, French West Indies, were included in this cross-sectional study. Pre- and postdialysis BP were recorded. Logistic regression methods and areas under the receiver operating characteristic curves were used. RESULTS: The mean age (+/- standard deviation) was 62.2 years (+/-10.2 years). A total of 24 subjects (30%) had one or more CV events. Sixteen (20%) had coronary disease, 15 (18.8%) cardiac failure, and seven (8.8%) had both. The medians [interquartile ranges] for predialysis PP was higher in patients with CV comorbidity than in patients without a history of CV at 84.5 mm Hg [74.5 to 92.3]v 69.5 mm Hg [61.0 to 79.5], P = .003. Areas under the ROC curves (95% confidence intervals) predialysis were significant only for SBP and PP at 0.70 (0.58 to 0.82) v 0.71 (0.59 to 0.83) without statistical differences. After adjustment for gender, age, body mass index, antihypertensive use, time on hemodialysis (>or=2 years), and hemoglobin rate, the odds ratio was significant only predialysis, and a higher odds ratio was found for PP at 2.25 (1.22 to 4.18), P = .01, than for SBP 1.97 (1.12 to 3.49), P = .02. CONCLUSIONS: Our results suggest that the strongest association of PP with CV morbidities should be considered in therapeutic strategies. These results show the necessity of targeting antihypertensive treatment to patients' predialysis blood pressure values.

Zinc is required for the catalytic activity of the human deubiquitinating isopeptidase T.

Two recombinant human isopeptidase T isoforms, ISOT-S and ISOT-L, differing by an insertion of 23 amino acids in ISOT-L, were previously classified as thiol proteases. Both contain one Zn2+-binding site of high-affinity, which is part of a cryptic nitrilo-triacetate-resistant pocket (site 1). A second Zn2+ site (site 2) was disclosed when both isoforms of the holoenzyme were incubated with an excess of Zn2+. The firmly bound Zn2+ of site 1 could be removed either slowly by dialysis against 1,10-phenanthroline at pH 5.5 or rapidly by treatment at pH 3.0 in the presence of 6 M urea followed by gel filtration at neutral pH. Zn2+ in site 1, but not in site 2, is essential for proteolytic activity because apoproteins were inactive. Inhibition of the catalytic activity was not due to a loss of ubiquitin binding capacity. CD spectra of both isoforms disclosed no major structural differences between the apo- and holoenzymes. The reconstitution of apoenzyme with Zn2+ under nondenaturing conditions at pH 5.5 completely restored enzymatic activity, which was indistinguishable from the reconstitution carried out in urea at pH 3.0. Thus, both human ISOTs are either thiol proteases with a local structural Zn2+ or monozinc metalloproteases that might use in catalysis a Zn2+-activated hydroxide ion polarized by Cys335.

Further characterization of the putative human isopeptidase T catalytic site.

The human isopeptidase T (isoT) is a zinc-binding deubiquitinating enzyme involved in the disassembly of free K48-linked polyubiquitin chains into ubiquitin monomers. The catalytic site of this enzyme is thought to be composed of Cys335, Asp435, His786 and His795. These four residues were site-directed mutagenized. None of the mutants were able to cleave a peptide-linked ubiquitin dimer. Similarly, C335S, D435N and H795N mutants had virtually no activity against a K48-linked isopeptide ubiquitin dimer, which is an isoT-specific substrate that mimics the K48-linked polyubiquitin chains. On the other hand, the H786N mutant retained a partial activity toward the K48-linked substrate, suggesting that the His786 residue might not be part of the catalytic site. None of the mutations significantly affected the capacity of isoT to bind ubiquitin and zinc. Thus, the catalytic site of UBPs could resemble that of other cysteine proteases, which contain one Cys, one Asp and one His.

A novel N(alpha)-acetyl alanine aminopeptidase from Allomyces arbuscula.

An N(alpha)-acetyl alanine aminopeptidase has been purified from the aquatic fungus Allomyces arbuscula. The apparent molecular mass of the enzyme was estimated to be 280 kDa by gel filtration through calibrated Sephacryl S300 column. In SDS-PAGE, the purified enzyme appeared as a single band of M(r) 80 kDa. Catalytic activity of the enzyme was inhibited by specific serine protease inhibitors, 3,4-DCI and APMSF, as well as SH reacting compounds, HgCl(2) and iodoacetate, indicating that the enzyme is a serine protease with some functional SH group(s) involved in the catalytic reaction. 3H-DFP was used to label the reactive serine of the enzyme. When the labeled protein was analyzed in SDS-PAGE, most of the label appeared in the M(r) 80 kDa band, however, a few additional faster migrating minor bands were also seen, probably representing a minor degradation product of the enzyme. The enzyme cleaved mainly N(alpha)-acetlylated alanine, although a small but negligible activity was also obtained with acetylated leucine and phenylalanine. The role of the enzyme in N-end rule proteolysis is discussed.