Dietary Intake and Nutritional Status in Diabetic and Nondiabetic Patients With Chronic Kidney Disease Stage 4-5 (NutriDiab Study).

OBJECTIVES: The aim of the present study was to assess the dietary intake and nutritional status of patients with chronic kidney disease (CKD) stage 4-5 according to the presence of diabetes. METHODS: This observational and cross-sectional study included adult patients with CKD stage 4-5 referred to a nephrology unit, between October 2018 and March 2019. Daily dietary intake was evaluated by 24-hour dietary inquiry and urine excretion. Nutritional status was assessed by measuring body composition using bioimpedance analysis and muscle function using handgrip strength. Undernutrition was considered using the protein energy wasting score. RESULTS: A total of 75 CKD patients were included, 36 (48%) of whom had diabetes; median age (interquartile range) was 71 (60-80) years. The median weight-adjusted dietary energy intake (DEI) was 22.6 (19.1-28.2) kcal/kg/day and the mean weight-adjusted dietary protein intake (DPI) was 0.86 ± 0.19 g/kg/day. There was no significant difference in DEI and DPI between patients with diabetes and those without, except for weight-adjusted DPI which was significantly lower in diabetic patients (P = .022). In univariate analysis, diabetes was associated with weight-adjusted DPI (coefficient [95% confidence interval] -0.237 [-0.446; -0.004] kcal/kg/day; P = .040), but this association did not remain significant in multivariate analysis. Nutritional status did not differ significantly between diabetic and nondiabetic patients except for lean tissue mass, which was lower in diabetic patients (P = .046). The proportion of patients with protein energy wasting was not significantly different between diabetic and nondiabetic patients (13.9% vs. 10.2%, respectively). CONCLUSIONS: In the present cohort, DPI and DEI were not significantly different between diabetic and nondiabetic CKD patients. Diabetes was not found to be associated with dietary intakes in CKD stage 4-5 patients.

Role of T CD4+ cells, macrophages, C-low threshold mechanoreceptors and spinal Cav 3.2 channels in inflammation and related pain-like symptoms in murine inflammatory models.

BACKGROUND AND PURPOSE: T-type calcium channels, mainly the Cav 3.2 subtype, are important contributors to the nociceptive signalling pathway. We investigated their involvement in inflammation and related pain-like symptoms. EXPERIMENTAL APPROACH: The involvement of Cav 3.2 and T-type channels was investigated using genetic and pharmacological inhibition to assess mechanical allodynia/hyperalgesia and oedema development in two murine inflammatory pain models. The location of Cav 3.2 channels involved in pain-like symptoms was studied in mice with Cav 3.2 knocked out in C-low threshold mechanoreceptors (C-LTMR) and the use of ABT-639, a peripherally restricted T-type channel inhibitor. The anti-oedema effect of Cav 3.2 channel inhibition was investigated in chimeric mice with immune cells deleted for Cav 3.2. Lymphocytes and macrophages from either green fluorescent protein-targeted Cav 3.2 or KO mice were used to determine the expression of Cav 3.2 protein and the functional status of the cells. KEY RESULTS: Cav 3.2 channels contributed to the development of pain-like symptoms and oedema in the two murine inflammatory pain models. Our results provided evidence of the involvement of Cav 3.2 channels located on C-LTMRs and spinal cord in inflammatory pain. Cav 3.2 channels located in T cells and macrophages contribute to the inflammatory process. CONCLUSION AND IMPLICATIONS: Cav 3.2 channels play crucial roles in inflammation and related pain, implying that targeting of Cav 3.2 channels with pharmacological agents could be an attractive and readily evaluable strategy in clinical trials, to relieve chronic inflammatory pain in patients.

Inhibition of Cav 3.2 calcium channels: A new target for colonic hypersensitivity associated with low-grade inflammation.

BACKGROUND AND PURPOSE: Abdominal pain associated with low-grade inflammation is frequently encountered in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) during remission. Current treatments are not very effective and new therapeutic approaches are needed. The role of CaV 3.2 channels, which are important in other chronic pain contexts, was investigated in a murine model of colonic hypersensitivity (CHS) associated with low-grade inflammation. EXPERIMENTAL APPROACH: Low doses of dextran sulfate sodium (DSS; 0.5%) were chronically administered to C57BL/6j mice in drinking water. Their inflammatory state was assessed by systemic and local measures of IL-6, myeloperoxidase, and lipocalin-2 using elisa. Colonic sensitivity was evaluated by the visceromotor responses to colorectal distension. Functional involvement of CaV 3.2 channels was assessed with different pharmacological (TTA-A2, ABT-639, and ethosuximide) and genetic tools. KEY RESULTS: DSS induced low-grade inflammation associated with CHS in mice. Genetic or pharmacological inhibition of CaV 3.2 channels reduced CHS. Cav3.2 channel deletion in primary nociceptive neurons in dorsal root ganglia (CaV 3.2Nav1.8 KO mice) suppressed CHS. Spinal, but not systemic, administration of ABT-639, a peripherally acting T-type channel blocker, reduced CHS. ABT-639 given intrathecally to CaV 3.2Nav1.8 KO mice had no effect, demonstrating involvement of CaV 3.2 channels located presynaptically in afferent fibre terminals. Finally, ethosuximide, which is a T-type channel blocker used clinically, reduced CHS. CONCLUSIONS AND IMPLICATIONS: These results suggest that ethosuximide represents a promising drug reposition strategy and that inhibition of CaV 3.2 channels is an attractive therapeutic approach for relieving CHS in IBS or IBD.

Phenotypic and Molecular Characterization of Brucella microti-Like Bacteria From a Domestic Marsh Frog (Pelophylax ridibundus).

Several Brucella isolates have been described in wild-caught and "exotic" amphibians from various continents and identified as B. inopinata-like strains. On the basis of epidemiological investigations conducted in June 2017 in France in a farm producing domestic frogs (Pelophylax ridibundus) for human consumption of frog's legs, potentially pathogenic bacteria were isolated from adults showing lesions (joint and subcutaneous abscesses). The bacteria were initially misidentified as Ochrobactrum anthropi using a commercial identification system, prior to being identified as Brucella spp. by MALDI-TOF assay. Classical phenotypic identification confirmed the Brucella genus, but did not make it possible to conclude unequivocally on species determination. Conventional and innovative bacteriological and molecular methods concluded that the investigated strain was very close to B. microti species, and not B. inopinata-like strains, as expected. The methods included growth kinetic, antimicrobial susceptibility testing, RT-PCR, Bruce-Ladder, Suis-Ladder, RFLP-PCR, AMOS-ERY, MLVA-16, the ectoine system, 16S rRNA and recA sequence analyses, the LPS pattern, in silico MLST-21, comparative whole-genome analyses (including average nucleotide identity ANI and whole-genome SNP analysis) and HRM-PCR assays. Minor polyphasic discrepancies, especially phage lysis and A-dominant agglutination patterns, as well as, small molecular divergences suggest the investigated strain should be considered a B. microti-like strain, raising concerns about its environmental persistence and unknown animal pathogenic and zoonotic potential as for other B. microti strains described to date.

Optimization of the synthesis of a key intermediate for the preparation of glucocorticoids.

A short and efficient synthesis, based on a one-step double elimination, of a key intermediate in the synthesis of various glucocorticosteroids has been developed. This method can be carried out on large scale for further industrial applications. The synthesis allowed us to identify a novel prednisolone derivative 10 and its anti-inflammatory activity was determined in an in vivo model of inflammation. In order to understand the regioselectivity of the double elimination under various conditions, mechanistic studies were undertaken and confirmed the experimental results. We also propose a mechanism for the formation of the new steroid 10 studied by molecular modeling.