Biodegradation of polyurethane acrylate with acrylated epoxidized soybean oil blend elastomers by Chaetomium globosum

This paper studies the biodegradation features of a novel blend of polyurethane acrylate-acrylated epoxidized soybean oil-based cross-linked polyurethane elastomers in the presence of the soft-rot fungus Chaetomium globosum. After the specimens were incubated at 28 °C for 90 and 130 days, the degree of fungal damage was measured by analysis of weight loss and mechanical properties. The biodegradation of the films was also evidenced by SEM and FTIR spectroscopic studies. After fungal attack, the FTIR spectra indicate a degradation of urethane and ester groups of the polyurethane and especially of the ester groups from the modified soybean oil part. The polyurethane blend films exposed to fungal attack suffered a loss in strength of up to 55% and a loss in elongation of up to 80%, depending on the content of acrylated epoxidized soybean oil. The biodegradation of the blends was also confirmed by SEM analyses. The biodegradation results show that samples with a high content of acrylated epoxidized soybean oil are more biodegradable than mere polyurethane acrylate. These biodegradable polymer blends present an optimum balance of physical properties and biodegradable properties with the potential for application as eco-friendly biomaterials.     

Vitamin D Deficiency—Prognostic Marker or Mortality Risk Factor in End Stage Renal Disease Patients with Diabetes Mellitus Treated with Hemodialysis—A Prospective Multicenter Study

BackgroundEnd stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.MethodsOur prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than12 ng/mL.ResultsPatients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.ConclusionsESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.     

Proximal Tubule Dysfunction Is Associated with Podocyte Damage Biomarkers Nephrin and Vascular Endothelial Growth Factor in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study

Background

There is an ongoing debate as to whether early diabetic nephropathy in Type 2 diabetes mellitus may be attributed to the glomerulus or to the proximal tubule. Urinary excretion of nephrin and vascular endothelial growth factor may increase even in the normoalbuminuria stage. In the course of diabetic nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin and vascular endothelial growth factor.

Materials and Methods

Two groups of consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric) and 21 healthy subjects were enrolled in a cross-sectional study and evaluated concerning the relation of proximal tubule dysfunction with the podocyte biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation end-products on this relation was also queried.

Results

Urinary alpha₁-microglobulin and kidney injury molecule-1 correlated with urinary albumin:creatinine ratio (R² = 0.269; p<0.001; R² = 0.125; p<0.001), nephrinuria (R² = 0.529; p<0.001; R² = 0.203; p<0.001), urinary vascular endothelial growth factor (R² = 0.709; p<0.001; R² = 0.360; p<0.001), urinary advanced glycation end-products (R² = 0.578; p<0.001; R² = 0.405; p<0.001), serum cystatin C (R² = 0.130; p<0.001; R² = 0.128; p<0.001), and glomerular filtration rate (R² = 0.167; p<0.001; R² = 0.166; p<0.001); nephrinuria and urinary vascular endothelial growth factor correlated with urinary albumin:creatinine ratio (R² = 0.498; p<0.001; R² = 0.227; p<0.001), urinary advanced glycation end-products (R² = 0.251; p<0.001; R² = 0.308; p<0.001), serum cystatin C (R² = 0.157; p<0.001; R² = 0.226; p<0.001), and glomerular filtration rate (R² = 0.087; p = 0.007; R² = 0.218; p<0.001).

Conclusions

In Type 2 diabetes mellitus there is an association of proximal tubule dysfunction with podocyte damage biomarkers, even in the normoalbuminuria stage. This observation suggests a potential role of the proximal tubule in urinary nephrin and urinary vascular endothelial growth factor processing in early diabetic nephropathy, a fact which could be related to advanced glycation end-products intervention. Podocyte damage and proximal tubule dysfunction biomarkers could be validated as a practical approach to the diagnosis of early diabetic nephropathy by further studies on larger cohorts.     

Effect of Cross-Linking Methods on Structure and Properties of Poly(ε-caprolactone) Stabilized Hydrogels Containing Biopolymers

Different dense and porous biodegradable matrices based on solely atelocollagen, or with different atelocollagen and hyaluronic acid derivative ratios, were obtained by varying feeding formulations, cross-linking reaction parameters, and preparative protocols. The compositions and methods for forming hydrogels through a combination of physical and chemical cross-linking processes are provided. The chemical cross-linking was mainly mediated by a synthetic component, a poly(ε-caprolactone) reactive derivative, aiming the development of new hybrid hydrogels with tailored characteristics by an appropriate use of the advantages offered by the included natural and synthetic components and the selection of the preparative procedure. The structure and morphology of the 3D hybrid materials were comparatively investigated by means of Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and environmental scanning electron microscopy (ESEM). FTIR and XRD analysis showed no signs of collagen denaturation during the formation of 3D structures. The influence of various factors, such as the chemical composition of the resulted hydrogels and their morphology, on water uptake and water vapor sorption, mechanical behavior, as well as on in vitro degradation characteristics, was systematically investigated. The experimental results point on the advantage offered by the high and modular physicochemical stability of the ternary hydrogels cross-linked by combined approaches. All newly developed materials show no hemolytic effect, which recommends them for potential biomedical applications.     

Ethanol-induced dysfunction of hepatocytes and leukocytes in patients without liver failure

The repeated intake of a great amount of ethanol is followed by functional and organic changes in the body. The intestinal absorption of alcohol is accompanied by an increased absorption of Gram negative bacteria endotoxins in the portal blood. In the liver, endotoxins stimulate CD14 receptors on the membrane of Kupffer cells, with a secondary inflammatory liver response, consisting in the secretion of proinflammatory cytokines and acute phase proteins. Simultaneously, alcohol metabolism in the hepatocytes by alcohol dehydrogenase, microsomal enzymes and catalase pathways determines a large production of ROS (reactive oxygen species), with secondary oxidative aggression on all liver cells: hepatocytes, Kupffer cells, endothelial sinusoidal cells, hepatic stellate cells and liver s lymphocytes. The oxidative aggression, as well as the intermediary products of the alcohol metabolism, cause a structural change of the antigenic structures of the liver and of the released proteins, that induces an immune response on the both pathways (humoral and cellular). The pathophysiological mechanisms and the paraclinical characteristics of the ethanol-induced liver failure are well known, so we were interested to study the patients with chronic alcoholism, but no clinical or paraclinical sign of liver failure, in order to describe the liver's protective mechanisms. For this reason, 153 patients with chronic alcoholism were divided into four test lots, in order to determine: the activity and the serum level of ceruloplasmin, plasma level of MDA (malondialdehyde), lactic and pyruvic acids, serum level of transferrin, alpha1-antitrypsin, CRP (C reactive protein), C3 fraction of the complement, IgA, IgG, IgM, IL-1beta, IL-6 and IL-8, cytosolic level of the cytochrome c in the circulating leukocytes. An immunophenotype study (as normal markers) on the peripheral blood lymphocytes was performed, too. The results demonstrate an important oxidative aggression induced by three sources: the alcohol metabolism in the hepatocytes, activated Kupffer cells and activated neutrophils that have infiltrated the liver, due to the chemoattractant effect of IL-8. This aggression induces apoptosis and necrosis of the liver cells. The major liver protective factor is, in our opinion, IL-6, due to its important antioxidant, antiapoptotic and proregenerative demonstrated actions. This protective effect of IL-6 is accompanied by antioxidant and antiprotease actions of ceruloplasmin, alpha1-antitrypsin and transferrin. We consider that an increased serum level of IL-6 accompanied by a decreased level of IL-1beta signify that antiapoptotic, antioxidant and proregenerative liver mechanisms prevail against proapoptotic and necrotic mechanisms. On the other hand, the ethanol-induced apoptosis of leukocytes (especially of the B cells) is very important, probably due to the absence of IL-6 protective action on these cells. The apoptosis of the circulating leukocytes is proved by their significant increase of the cytochrome c cytosolic level. The ethanol-induced liver immune response is predominantly cellular, as proved by the decreased ratio T helper (CD4+)/T cytotoxic (CD8+) in the peripheral blood. It is very important to observe that these significant immunologic changes appear before clinical or paraclinical signs of hepatic failure start. All these parameters were investigated in three groups of patients: chronic alcoholics, chronic alcoholics in the first 24 hours of the withdrawal and chronic alcoholics with acute alcohol intoxication, so the aggression types and the protective mechanisms were measured and differentiated in each "ethanolic status".     

Neurotrophin-3, TNF-alpha and IL-6 relations in serum and cerebrospinal fluid of ischemic stroke patients

Pro-inflammatory cytokines and neurotrophins in the central nervous system (CNS) have been recognized as mediators of both neurodegenerative and neuroprotective mechanisms in a number of CNS pathologies. A rapid, sustained elevation of these molecules was recently reported after traumatic and ischemic brain injury. Inflammatory mechanisms and immune activation have been hypothesized to play a role in the pathogenesis of cerebral ischemia. Stroke is the third largest cause of death next to heart disease and cancer in the world, and it is an important cause of death and disability in developed countries. Role of excitatory amino acids receptors activation, calcium overload, nitric oxide and oxidative stress in the pathogenesis of ischemic brain damage is well established. Stroke may modulate peripheral neurotrophic factors levels. In experimental animal models, neurotrophin-3 (NT-3) has been shown to be produced by glial cells as an adaptability response to hypoxia. In spite of substantial research and significant number of neuroprotective drugs that have been developed to limit ischemic brain damage and to improve the outcome for stroke patients, no specific therapy for stroke is available. The neurotrophins have been proposed as therapeutic agents for the treatment of neurodegenerative disorders and ischemic injury. In the present work, we investigated the possible correlation of NT-3 with tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the serum and cerebrospinal fluid (CSF) from patients with ischemic stroke (IS).