Development of HLA-matched vascular grafts utilizing decellularized human umbilical artery

Worldwide, there is a great need of small diameter vascular grafts that can be used in human disorders such as cardiovascular and peripheral vascular disease. Until now, severe adverse reactions are caused from the use of synthetic or animal derived grafts, while the use of autologous vessels is restricted only in a small number of patients. The limited availability of the vessels might be resolved by the use of HLA-matched vascular grafts utilizing the decellularized human umbilical arteries. In this study, human umbilical arteries were decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype of the repopulated grafts, analyzed by Next Generation Sequencing technology, indicated their successful production. The HLA-matched vascular grafts could be generated efficiently and might be used in personalized medicine.     

Altered long chain fatty acids composition in Duchenne muscular dystrophy erythrocytes

BACKGROUND: Biochemical abnormalities, increased efflux of soluble enzymes and muscle proteins, and altered permeability of muscle membranes imply the presence of a disorganized erythrocyte membrane in Duchenne muscular dystrophy (DMD). The purpose of the present study was to investigate this hypothesis of a generalized membrane defect. MATERIALS AND METHODS: Twenty-five patients with the disease were analyzed for their erythrocyte lipid composition and for alterations in their fatty acid content compared to twenty-five healthy subjects. RESULTS: DMD patients showed a decreased concentration of total phospholipids compared to healthy volunteers, with striking fluctuations in concentrations of erythrocyte long chain fatty acids. Specifically, the unsaturated fatty acids such as oleic, linoleic and arachidonic acids were significantly decreased in the disease, whereas the saturated fatty acid, palmitic acid was increased in DMD patients compared to healthy controls. CONCLUSION: Our findings suggest an abnormal fatty acid composition and disorganization of erythrocyte membrane in patients with DMD associated with possible functional alterations.     

Structure elucidation and conformational study of V8: a novel synthetic non peptide AT(1) antagonist

AT₁ antagonists constitute the most recent class of antihypertensive drugs which act through the Renin Angiotensin System (RAS). In an effort to comprehend their stereoelectronic features, a study was initiated to compare the conformational properties of drugs already marketed for the treatment of hypertension with synthetic ones, possessing common structural characteristics. In this study, the synthetic AT₁ antagonist V8 is structurally elucidated and its conformational properties are studied through a combination of NMR spectroscopy and computational analysis. Its conformational properties are compared with those of the structurally similar prototype AT₁ antagonist losartan.     

Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system

BACKGROUND: CKS257 (Salmonella typhimurium SL1344 DeltaphoP/phoQDelta aroA Deltaasd DeltastrA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag. METHODS: HIV Gag was expressed as a fusion protein of a Salmonella Type III secretion system protein SopE, from a balanced lethal asd-based plasmid. Eighteen healthy adults were given single escalating oral doses of 5 x 10(6) to 1 x 10(10)CFU of CKS257 and were monitored for clinical events, shedding and immune responses. RESULTS: Adverse events were mild except at the highest dose. Volunteers shed the organism an average of 5.1 days (range 0-13 days). Eighty-three percent (15/18) of subjects had a mucosal immune response to Salmonella LPS and flagella by IgA ELISPOT assay. Seventy-two percent (13/18) of subjects seroconverted to Salmonella antigens. No volunteer had a response to recombinant Gag as measured by serology, IgA ELISPOT, or immediate ex vivo gamma-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving >or=5 x 10(8)CFU had a response to HIV peptides in a cultured gamma-interferon ELISPOT assay. CONCLUSIONS: Although immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development.     

Evaluation of spiral computed tomography versus ventilation/perfusion scanning in patients clinically suspected of pulmonary embolism

OBJECTIVE: To prospectively evaluate the diagnostic accuracy of spiral computed tomography (CT) versus ventilation/perfusion (V/Q) scanning in the examination of patients clinically suspected of having pulmonary embolism (PE). PATIENTS AND METHODS: Sixty-three patients, presenting to the emergency department and departments of radiology and nuclear medicine of a large hospital, highly suspected of having PE, underwent sequential imaging testing with V/Q scanning and contrast-enhanced spiral CT, in addition to other clinical and laboratory tests. RESULTS: PE was diagnosed in 42 (66.7%) of the 63 patients. Thirty-nine of these 42 patients had positive findings in their CT scans, while 18 of the remaining 21 patients without PE had negative findings in their spiral CT [sensitivity, 92.9%, specificity, 85.7% Positive Predictive Value (PPV), 92.9%, Negative Predictive Value (NPV), 85.7%]. V/Q scans showed high-probability of PE in 24 of the 42 patients with PE and were negative in 9 of the remaining 21 patients without PE (sensitivity, 571%, specificity, 42.9%, PPV, 66.7%, NPV, 33.3%). There were statistically significant differences in specificity and sensitivity favoring spiral CT among men and women patients or patients > 50 years old. Fifty-four patients (85.7%) rated their satisfaction towards spiral CT as 'good' or 'very good', whereas the respective rate for V/Q scanning was only 14.3%. CONCLUSION: Spiral CT has an excellent sensitivity, specificity, PPV and NPV for the diagnosis of PE and it could be used as the first-line imaging modality in patients suspected of PE.     

Poly(N,N‐dimethylacrylamide)‐block‐Poly(L‐lysine) Hybrid Block Copolymers: Synthesis and Aqueous Solution Characterization

Four poly(N,N‐dimethylacrylamide)‐block‐poly(L ‐lysine) (PDMAM‐block‐PLL) hybrid diblock copolymers and two PLL homo‐polypeptides are prepared via ROP of ε‐trifluoroacetyl‐L ‐lysine N‐carboxyanhydride initiated by primary amino‐terminated PDMAM and n‐hexylamine respectively. The PLL blocks render the copolymers a multi‐responsive behavior in aqueous solution due to their conformational transitions from random coil to α‐helix with increasing pH, and from α‐helix to β‐sheet upon heating. The random coil‐to‐α‐helix transition is found to depend on the PLL length: the longer the peptide segment, the more readily the transition occurred. The same trend was observed for the α‐helix‐to‐β‐sheet transition, which was found to be inhibited for short polypeptides unless conjugated with the PDMAM block.

     

A Systematic Review of Bisphenol A from Dietary and Non-Dietary Sources during Pregnancy and Its Possible Connection with Fetal Growth Restriction: Investigating Its Potential Effects and the Window of Fetal Vulnerability

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is increasingly hypothesized to be a factor contributing to changes in fetal growth velocity. BPA exposure may be environmental, occupational, and/or dietary, with canned foods and plastic bottles contributing significantly. Our systematic review aims to evaluate the current literature and to investigate the role of BPA in abnormal fetal growth patterns. A search was conducted in the PubMed and Cochrane databases. A total of 25 articles met the eligibility criteria and were included in this systematic review. Eleven of them failed to show a clear relationship between BPA and abnormal fetal growth. The majority of the remaining studies (9/14) found an inverse association of BPA with indicators of fetal growth, whereas three studies suggested increased fetal growth, and two studies produced contradictory findings. Of note, both of the studies that collected a sample (amniotic fluid) directly reflecting BPA concentration in the fetus during the first half of pregnancy revealed an inverse association with birth weight. In conclusion, there is mounting evidence that combined exposure to BPA from dietary and non-dietary sources during pregnancy may contribute to abnormal fetal growth; a tendency towards fetal growth restriction was shown, especially when exposure occurs during the first half.     

Effect of exogenous catecholamines on tumor necrosis factor alpha, interleukin-6, interleukin-10 and beta-endorphin levels following severe trauma

Cytokines and endogenous opioids are mediators of the post traumatic inflammatory response. The aim of this study was to determine the effect of exogenous catecholamines on tumor necrosis factor alpha (TNFa), interleukin-6 (IL-6), interleukin-10 (IL-10) and beta(beta)-endorphin levels in patients with severe trauma, during the first 24 h after injury. Forty four traumatized patients with haemorrhage class III and IV were included in the study. Patients were divided in two groups: Group 1 (adrenergic, n=22) and Group 2 (non adrenergic, n=22), depending on the use of exogenous catecholamines. Blood samples were collected at 0, 2, 4 and 24 h time points. Baseline values were different between the two groups, but an altered pattern of release was observed for TNFa, IL-6, IL-10 and beta-endorphin levels in patients treated with catecholamines. ICU stay was longer for the adrenergic group, while survival after 1 month was significantly lower. Findings support an altered pattern of cytokine release during the early phase after trauma, probably due to catecholamine presence.