Adiponectin and C-reactive protein are positively associated with microalbuminuria in an adult Caucasian population

Objective: Microalbuminuria (MAU) is a marker of early kidney injury and cardiovascular risk. We assessed the association of MAU with plasma adiponectin, leptin and hsCRP, as inflammatory markers, accounting for hypertension, diabetes and obesity. Design and methods: Population based, cross-sectional study in Caucasian subjects aged 35 to 75 years in Lausanne, Switzerland. MAU, measured on spot morning urine, was used either as a continuous (MAU) or dichotomized variable (MA defined as MAU >2.5 and >3.5 mg/mmol creatinine in men and women, respectively). Results: The 2955 women (age 53.3 ± 10.7, mean ± SD years) had mean body mass index (BMI) 24.9 ± 4.5 kg/m. The 2479 men (age 53.1 ± 10.8 years) had mean BMI 27.0 ± 3.9 kg/m². Median hsCRP was 1.3 and 1.3 mg/L, median adiponectin 6.2 and 10.6 mg/mL in men and women, respectively. MA prevalence was 4.9% in women and 9.8% in men. In multivariate regression analysis adjusting for potential confounders (age, sex, hypertension, diabetes, eGFR, BMI, percent fat mass, insulin and smoking), log-transformed MAU was positively associated with hsCRP (P <0.001) and adiponectin (P = 0.002), but not with leptin. The association of adiponectin with MAU was stronger in subjects with low hsCRP, and vice versa (P interaction <0.001). Conclusion: Adiponectin and hsCRP are significant positive determinants of MAU, independently of diabetes, hypertension and fat mass. A negative interaction between hsCRP and adiponectin was found for their effect on MAU. Whether hyperadiponectinemia represents an adequate protective response to vascular stress or has negative causal impact on the development of MAU should be assessed in further studies.

Effects of a whey protein supplementation on intrahepatocellular lipids in obese female patients.

Background & aims: High protein diets have been shown to improve hepatic steatosis in rodent models and in high-fat fed humans. We therefore evaluated the effects of a protein supplementation on intrahepatocellular lipids (IHCL), and fasting plasma triglycerides in obese non diabetic women.Methods: Eleven obese women received a 60 g/day whey protein supplement (WPS) for 4-weeks, while otherwise nourished on a spontaneous diet, IHCL concentrations, visceral body fat, total liver volume (MR), fasting total-triglyceride and cholesterol concentrations, glucose tolerance (standard 75 g OGTT), insulin sensitivity (HOMA IS index), creatinine clearance, blood pressure and body composition (bio-impedance analysis) were assessed before and after 4-week WPS.Results: IHCL were positively correlated with visceral fat and total liver volume at inclusion. WPS decreased significantly IHCL by 20.8 +/- 7.7%, fasting total TG by 15 +/- 6.9%, and total cholesterol by 7.3 +/- 2.7%. WPS slightly increased fat free mass from 54.8 +/- 2.2 kg to 56.7 +/- 2.5 kg, p = 0.005). Visceral fat, total liver volume, glucose tolerance, creatinine clearance and insulin sensitivity were not changed.Conclusions: WPS improves hepatic steatosis and plasma lipid profiles in obese non diabetic patients, without adverse effects on glucose tolerance or creatinine clearance. Trial Number: NCT00870077, ClinicalTrials.gov (C) 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Kinetoplastid membrane protein-11 is present in promastigotes and amastigotes of Leishmania amazonensis and its surface expression increases during metacyclogenesis

Kinetoplastid membrane protein-11 (KMP-11), a protein present in all kinetoplastid protozoa, is considered a potential candidate for a leishmaniasis vaccine. A suitable leishmaniasis vaccine candidate molecule must be expressed in amastigotes, the infective stage for mammals. However, the expression of KMP-11 in Leishmania amastigotes has been a subject of controversy. We evaluated the expression of this molecule in logarithmic and stationary growth phase promastigotes, as well as in amastigotes, of Leishmania amazonensis by immunoblotting, flow cytometry and immunocytochemistry, using a monoclonal antibody against KMP-11. We found that KMP-11 is present in promastigotes and amastigotes. In both stages, the protein was found in association with membrane structures (at the cell surface, flagellar pocket and intracellular vesicles). More importantly, its surface expression is higher in amastigotes than in promastigotes and increases during metacyclogenesis. The increased expression of KMP-11 in metacyclic promastigotes, and especially in amastigotes, indicates a role for this molecule in the parasite relationship with the mammalian host. The presence of this molecule in amastigotes is consistent with the previously demonstrated immunoprotective capacity of vaccine prototypes based on the KMP-11-coding gene and the presence of humoral and cellular immune responses to KMP-11 in Leishmania-infected humans and animals.

Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein.

Natural killer (NK) cells are at the crossroad between innate and adaptive immunity and play a major role in cancer immunosurveillance. NK cell stimulation depends on a balance between inhibitory and activating receptors, such as the stimulatory lectin-like receptor NKG2D. To redirect NK cells against tumor cells, we designed bifunctional proteins able to specifically bind tumor cells and to induce their lysis by NK cells, after NKG2D engagement. To this aim, we used the 'knob into hole' heterodimerization strategy, in which 'knob' and 'hole' variants were generated by directed mutagenesis within the CH3 domain of human IgG1 Fc fragments fused to an anti-CEA or anti-HER2 scFv or to the H60 murine ligand of NKG2D, respectively. We demonstrated the capacity of the bifunctional proteins produced to specifically coat tumor cells surface with H60 ligand. Most importantly, we demonstrated that these bifunctional proteins were able to induce an NKG2D-dependent and antibody-specific tumor cell lysis by murine NK cells. Overall, the results show the possibility to redirect NK cytotoxicity to tumor cells by a new format of recombinant bispecific antibody, opening the way of potential NK cell-based cancer immunotherapies by specific activation of the NKG2D receptor at the tumor site.