A colloidal nano-immunosensor based on gold nanoparticles covered in their surface with protein A and the immunoglobulin anti-kidney injury molecule-1 was prepared and tested in human urine to ...identify a biomarker that diagnose acute kidney injury. The urine was obtained from patients with cancer treated with cisplatin, diagnosed with acute kidney injury, and from healthy individuals. Fourier-transform infrared spectroscopy analysis showed important spectral differences between both types of groups, primarily for the intervals from 1750 to 1500 cm
−1
and from 1000 to 891 cm
−1
where the amide I group (C = O) and the glycosylated functional groups of this protein absorb. The principal component analysis applied to the vibrational signals obtained with the nano-immunosensor allows adequate discrimination of urine from patients with acute kidney injury from samples from healthy individuals. The simplicity of the proposed method, from the preparation of the nano-immunosensor to the spectral and chemometric analysis, may make this method an interesting alternative to practically diagnose acute kidney injury using a small volume of urine.
Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had ...been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney).
Proximal tibiofibular instability is a rare condition for which treatment is poorly codified. A 21-year-old patient, a leisure sportswoman, presented a post-traumatic anterolateral instability of the ...proximal tibiofibular articulation without cartilage lesion. We propose an original surgical technique based on a review of the literature that combines an anatomical ligamentoplasty of the proximal tibiofibular joint and a proximal fibular diaphyseal osteotomy to reduce the distal tibiofibular mechanical stresses. This original technique allows a favorable evolution with recovery of professional and sports activities at 6 months.
Bile acids regulate glucose homeostasis and lipid metabolism. Further, the levels of bile acids can be influenced by the intake of dairy products. Although the serum proteome can provide information ...on the biological pathways associated with different metabolites, it is unknown whether the intake of dairy modifies such associations between bile acids and the proteome. The objectives of this study were to examine plasma bile acid profiles, find the correlations between bile acids and lipid as well as glycemic markers, and to uncover the correlation between bile acids and proteins after high dairy (HD) and adequate dairy (AD) intake among 25 overweight individuals with hyperinsulinemia. In this randomized crossover-trial study, hyperinsulinemia adults were randomized to both HD (≥4 servings/day) and AD (≤2 servings/day) for 6 weeks. Measurements and analyses were performed on before- as well as after- AD and HD conditions. The results indicated that plasma 7α-hydroxy-4-cholesten-3-one (7AC4) increased after HD in comparison with before HD intake (p = 0.03). After adjusting for BMI, age, and sex, 7AC4 positively correlated with triglyceride levels in the pre-AD (r = 0.44; p = 0.03) and post-HD (r = 0.42; p = 0.04). Further, 7AC4 correlated positively with proteins associated with high-density lipoprotein particle remodeling pathway and reverse cholesterol transport only after HD consumption. Thus, the consumption of higher dairy intake modifies the association between 7AC4—a biomarker for bile acid synthesis—and serum proteins involved in cholesterol clearance. Overall, higher dairy consumption may have a positive effect on cholesterol metabolism in subjects at risk of type 2 diabetes.
Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake ...preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects.
The current evolution of surgical practices is increasingly trending toward hyper-specialization. For military surgeons, their practice in France does not differ from their civilian counterparts. In ...contrast, in external operations, they have to deal with specific war injuries in austere conditions. They are also required to take care of local populations. Therefore, specific training is necessary, and the French Military Health Service Academy (Ecole du Val-de-Grâce) Paris has set up a specific training called Advanced Course for Deployment Surgery (ACDS) in 2007. The aim of this study is to assess the relevance of this teaching regarding pathologies encountered during current conflicts.
The activity of deploying orthopedic surgeons during the three recent major external operations (Afghanistan, Mali, and Central African Republic) has been retrospectively recorded in terms of global volume, types of trauma, status of patients who had been operated on, and indications. These data have been compared with teaching during the ACDS.
Our study found a high variability in terms of operating volume, types of trauma, patients' statuses, and types of operations performed depending on the operation theaters. The volume of surgical activity carried out within Role 3 is much more important than that in Role 2 with more than half of the surgeries performed as scheduled surgery to the benefit of the local population. Within advanced Role 2 surgical structures deployed in Mali and Central Africa, more than 70% of the activity was performed as emergencies. Surgical indications were varied, ranging from emergency surgery to limb reconstructive surgery. A lot of non-orthopedic procedures such as vascular repairs and decompressive craniotomies were also performed. All of the encountered pathologies were taught during ACDS.
The large variety and technical nature of the performed operations requires the training of highly qualified military orthopedic surgeons with both experience in war surgery and management of after-effects and complications. Orthopedists are also required to carry out procedures dealing with neurosurgery, general, and/or vascular surgery on missions. These data highlight the complexity of military surgeons' training along with the hyper-specialization of the civilian medical world. For more than 10 yr, French military surgeons have benefited from a training program called ACDS to meet these objectives. This initial training seems to be appropriated adapted in view of the managed pathologies.
Cadmium (Cd
) in the environment is a significant health hazard. Chronic low Cd
exposure mainly results from food and tobacco smoking and causes kidney damage, predominantly in the proximal tubule. ...Blood Cd
binds to thiol-containing high (e.g., albumin, transferrin) and low molecular weight proteins (e.g., the high-affinity metal-binding protein metallothionein, β2-microglobulin, α1-microglobulin and lipocalin-2). These plasma proteins reach the glomerular filtrate and are endocytosed at the proximal tubule via the multiligand receptor complex megalin:cubilin. The current dogma of chronic Cd
nephrotoxicity claims that Cd
-metallothionein endocytosed via megalin:cubilin causes renal damage. However, a thorough study of the literature strongly argues for revision of this model for various reasons, mainly: (i) It relied on studies with unusually high Cd
-metallothionein concentrations; (ii) the
of megalin for metallothionein is ~10
-times higher than (Cd
)-metallothionein plasma concentrations. Here we investigated the uptake and toxicity of ultrafiltrated Cd
-binding protein ligands that are endocytosed via megalin:cubilin in the proximal tubule. Metallothionein, β2-microglobulin, α1-microglobulin, lipocalin-2, albumin and transferrin were investigated, both as apo- and Cd
-protein complexes, in a rat proximal tubule cell line (WKPT-0293 Cl.2) expressing megalin:cubilin at low passage, but is lost at high passage. Uptake was determined by fluorescence microscopy and toxicity by MTT cell viability assay. Apo-proteins in low and high passage cells as well as Cd
-protein complexes in megalin:cubilin deficient high passage cells did not affect cell viability. The data prove Cd
-metallothionein is not toxic, even at >100-fold physiological metallothionein concentrations in the primary filtrate. Rather, Cd
-β2-microglobulin, Cd
-albumin and Cd
-lipocalin-2 at concentrations present in the primary filtrate are taken up by low passage proximal tubule cells and cause toxicity. They are therefore likely candidates of Cd
-protein complexes damaging the proximal tubule via megalin:cubilin at concentrations found in the ultrafiltrate.
Bile acid (BA) metabolism is tightly controlled by nuclear receptor signaling to coordinate regulation of BA synthetic enzymes and transporters. Here we reveal a molecular cascade consisting of the ...antiapoptotic protein BCL2, nuclear receptor Shp, and long non-coding RNA (lncRNA) H19 to maintain BA homeostasis. Bcl2 was overexpressed in liver of C57BL/6J mice using adenovirus mediated gene delivery for two weeks. Hepatic overexpression of Bcl2 caused drastic accumulation of serum BA and bilirubin levels and dysregulated BA synthetic enzymes and transporters. Bcl2 reactivation triggered severe liver injury, fibrosis and inflammation, which were accompanied by a significant induction of H19. Bcl2 induced rapid SHP protein degradation via the activation of caspase-8 pathway. The induction of H19 in Bcl2 overexpressed mice was contributed by a direct loss of Shp transcriptional repression. H19 knockdown or Shp re-expression largely rescued Bcl2-induced liver injury. Strikingly different than Shp, the expression of Bcl2 and H19 was hardly detectable in adult liver but was markedly increased in fibrotic/cirrhotic human and mouse liver. We demonstrated for the first time a detrimental effect of Bcl2 and H19 associated with cholestatic liver fibrosis and an indispensable role of Shp to maintain normal liver function.
The proximal tubule (PT) is the major target of cadmium (Cd
) nephrotoxicity. Current dogma postulates that Cd
complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated ...endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney. Nevertheless, there is evidence that the distal parts of the nephron are also sensitive to damage induced by Cd
. In rodent kidneys, another receptor for protein endocytosis, the 24p3 receptor (24p3R), is exclusively expressed in the apical membranes of distal tubules (DT) and collecting ducts (CD). Cell culture studies have demonstrated that RME and toxicity of CdMT and other (metal ion)-protein complexes in DT and CD cells is mediated by 24p3R. In this study, we evaluated the uptake of labeled CdMT complex through 24p3R after acute kidney injury (AKI) induced by gentamicin (GM) administration that disrupts PT function. Subcutaneous administration of GM at 10 mg/kg/day for seven days did not alter the structural and functional integrity of the kidney's filtration barrier. However, because of PT injury, the concentration of the renal biomarker Kim-1 increased. When CdMT complex coupled to FITC was administered intravenously, both uptake of the CdMT complex and 24p3R expression in DT increased and also colocalized after PT injury induced by GM. Although megalin decreased in PT after GM administration, urinary protein excretion was not changed, which suggests that the increased levels of 24p3R in the distal nephron could be acting as a compensatory mechanism for protein uptake. Altogether, these results suggest that PT damage increases the uptake of the CdMT complex through 24p3R in DT (and possibly CD) and compensate for protein losses associated with AKI.
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