Factors associated with chronic kidney disease in patients with diabetes in French Guiana.

Introduction: With over half of the population living under the poverty threshold, the social and health context in French Guiana is more difficult than in mainland France. The prevalence of diabetes is twice as great and end-stage renal failure is 45% higher than in mainland France. Objective: Our objective was to describe the profile of diabetic patients with chronic kidney disease in French Guiana and search for possible risk factors. Method: We conducted a multicenter cross-sectional observational study based on the CODIAM cohort (Cohort of Diabetes in French Amazonia). We analyzed 1,287 patients followed up between May 2019 and June 2021 at Cayenne Hospital, Saint Laurent Hospital, and delocalized health centers. Results: In our cohort, chronic kidney disease was present after an average of 12 years of diabetes. Compared with the French population, 41% of diabetic patients had chronic kidney disease (i.e., 12% more), and had an average age of 56 years (i.e., 10 years younger). Forty-eight per cent of these patients were obese (i.e., 7% more). Seventy-four per cent of patients were precarious and 45% were foreigners but neither was associated with chronic kidney disease, contrary to countries where the health system is not universal. Conclusion: Screening of patients with chronic kidney disease among diabetics in French Guiana remains a real challenge. Patients were younger and more obese than in other French territories. In this cohort, precariousness and immigration were not associated with the presence of chronic kidney disease. However, particular attention should be paid to hypertensive patients and those over 65 years of age, which are, with diabetes itself, the two most obvious risk factors for developing chronic kidney disease among diabetic patients in our territory.

Impact of Lipoprotein(a) on Macrovascular Complications of Diabetes in a Multiethnic Population in the French Amazon.

Background and Aims: In French Guiana, the prevalence of diabetes is around 10%, and cardio and neurovascular pathologies are the first medical cause of early mortality. Lipoprotein(a) (Lp(a)) is described in the literature as a risk factor independent of other cardiovascular risk factors, but there are important interindividual differences, especially according to ethnicity. The objective of this study was to investigate the association of Lp(a) and macrovascular complications in a multiethnic population of patients with diabetes in the French Amazon. Materials and Methods: Since May 2019, 1243 patients were screened 806 of whom had Lp(a) determination. We compared the prevalence of macrovascular complications in three groups according to Lp(a) concentration: between 0 and 75 mg/mL, between 76 and 300 mg/mL, and >300 mg/mL. Results: 712 patients in the study had type 2 diabetes (88.34% of the sample). A history of hypertension was significantly associated with greater Lp(a) levels. Lp(a) concentration was greater among Creole ethnic groups. No association was found between Lp(a) levels and macrovascular complications in the Lp(a) > 300 mg/mL group. Conclusions: These results do not replicate findings in mostly Caucasian populations suggesting that the Lp(a) threshold for, or the link with, cardiovascular risk may be different given the predominantly African origin of the French Guianese population. Further studies should study genetic polymorphisms in our population.

Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage.

Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 µm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.

Disparate impact of oxidative host defenses determines the fate of Salmonella during systemic infection in mice.

Reactive oxygen and nitrogen species function in host defense via mechanisms that remain controversial. Pathogens might encounter varying levels of these species, but bulk measurements cannot resolve such heterogeneity. We used single-cell approaches to determine the impact of oxidative and nitrosative stresses on individual Salmonella during early infection in mouse spleen. Salmonella encounter and respond to both stresses, but the levels and impact vary widely. Neutrophils and inflammatory monocytes kill Salmonella by generating overwhelming oxidative stress through NADPH oxidase and myeloperoxidase. This controls Salmonella within inflammatory lesions but does not prevent their spread to more permissive resident red pulp macrophages, which generate only sublethal oxidative bursts. Regional host expression of inducible nitric oxide synthase exposes some Salmonella to nitrosative stress, triggering effective local Salmonella detoxification through nitric oxide denitrosylase. Thus, reactive oxygen and nitrogen species influence dramatically different outcomes of disparate Salmonella-host cell encounters, which together determine overall disease progression.

Calcium phosphate mineralization beneath monolayers of poly(n-butylacrylate)-block-poly(acrylic acid) block copolymers.

Amphiphilic poly(acrylic acid)-block-poly(n-butylacrylate) block copolymer films at the air-water interface have been mineralized with calcium phosphate. The polymers form stable monolayers at the free surface. Their stability is virtually independent of ion strength or pH changes in the subphase. The outcome of calcium phosphate crystallization depends on the calcium and phosphate concentrations, the stirring rate of the subphase, and the subphase pH. At low calcium and phosphate concentrations (2 mM), uniform polymer-calcium phosphate hybrid films form. Higher calcium and phosphate concentrations yield less ordered films, which often contain large blocks of material beneath the polymer monolayer. Occasionally, also filaments similar to samples described by Peytcheva et al. (Colloid Polym. Sci., 2002, 280, 218) are observed. Films mineralized at pH values below ca. 6 contain particles that are a few nanometers apart and the resulting films retain some flexibility. Films grown above pH 6 have a higher degree of mineralization. They are stiff and tend to break upon mechanical stress. Overall, the paper illustrates that low calcium phosphate supersaturation in the subphase and a well-defined (but not crystalline) interface are crucial for controlling calcium phosphate mineralization. As a result, the current study could serve as a model for biological mineralization which is more closely related to Nature than films made from e.g. detergents or low molecular mass compounds.

Antioxidant nanoreactor based on superoxide dismutase encapsulated in superoxide-permeable vesicles.

We designed and tested an antioxidant nanoreactor based on encapsulation of Cu,Zn superoxide dismutase in amphiphilic copolymer nanovesicles, the membranes of which are oxygen permeable. The nanovesicles, made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline), successfully encapsulated the protein during their self-assembling process, as proved by confocal laser-scanning microscopy and fluorescence-correlation spectroscopy. Electron paramagnetic resonance spectroscopy and circular dichroism analyses showed that no structural changes appeared in the protein molecules once inside the inner space of the nanovesicles. The function of this antioxidant nanoreactor was tested by pulse radiolysis, which demonstrated that superoxide dismutase remains active inside the nanovesicles and detoxifies the superoxide radical in situ. The membrane of our triblock copolymer nanovesicles plays a double role, both to shield the sensitive protein and to selectively let superoxide and dioxygen penetrate to its inner space. This simple and robust hybrid system provides a selective shielding of sensitive enzymes from proteolytic attack and therefore a new direction for developing drug delivery applications.