The association of endothelin-1 gene polymorphism and its plasma levels with hypertension and coronary atherosclerosis

IntroductionEndothelin-1 (ET-1) is the most potent among all vasoconstrictors, and its association with cardiovascular diseases has been reported before. Our aim was to investigate the association of ET-1 plasma level and its gene polymorphisms (rs5370 and rs10478694) with hypertension and coronary atherosclerosis (CA).Material and methodsThis study was carried out on 128 women and 132 men, who were divided into 4 groups: hypertensive without atherosclerosis (H+A–); hypertensive with atherosclerosis (H+A+); non-hypertensive with atherosclerosis (H–A+); and non-hypertensive without atherosclerosis (control group). Endothelin-1 plasma levels were measured by ELISA, and gene polymorphisms were detected by polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) methods. Coronary artery diseases (CAD) were then defined based on angiography data.ResultsThe ET-1 plasma level was significantly higher in the H+A+ group in comparison with the other groups, especially H+A–. Comparing people with CA and those without it, the highest frequency level of the T allele of rs5370 was found in people with CA. Significantly higher frequencies of the 3A allele were detected in hypertensive patients in comparison with non-hypertensive individuals, when analyzing rs10478694.ConclusionsEndothelin-1 plasma level shows a direct association with the risk of CA development. The T allele of rs5370 can be regarded as a risk factor for CA development. The 3A allele of rs10478694 can be associated with the risk of hypertension; therefore, it can be concluded that ET-1 and its gene polymorphisms play an important role in CA development and hypertension observed in the south-eastern populations of Iran.     

Silicone Additive Manufactured Indices Performed from a Virtual Diagnostic Waxing for Direct Composite Diastema Closure Combined with Resin Infiltration Technique on White Spot Lesions: A Case Report

The present article describes the resin infiltration technique to address white spots lesions presented on anterior and premolar teeth of a young patient after orthodontic treatment and the digital workflow for planning a diastema closure on the maxillary anterior teeth using facial photographs, an intraoral scanner, a facially driven diagnostic waxing using a dental computer‐aided design (CAD) software, and 3‐piece additive manufactured (AM) clear silicone indices. The virtual design of the silicone indices was completed using an open‐source CAD software and included a flexible clear buccal piece, flexible clear lingual piece, and rigid clear custom tray. The unique 3‐piece index design allows a horizontal path of insertion, controlled uniform thickness of the indices, flexible and rigid material properties combination, accurate translation of the diagnostic waxing into the patient´s mouth, and digital storage of the designs.     

Histopathological changes of gastric mucosa following oral administration of fumonisin B1 in mice

Fumonisin B1 is a common secondary metabolite produced by Fusarium moniliforme that occurs in corn and corn-based foods. This mycotoxin is toxic to many species of laboratory and domestic animals and is known to induce a variety of diseases such as hepatic cancer and renal and hepatic dysfunction. The structure of fumonisin B1 (FB1) resembles sphingolipids so it can inhibit synthesis of ceramide, an enzyme in the sphingolipid biosynthetic pathway. This inhibition leads to the disruption of sphingolipid metabolism and increased levels of sphinganine and sphingosine (sphingoid bases) in the serum of treated animals. It is believed that the toxicity effect of fumonisin B1 is the result of these sphingoid bases. In the present research, mice were treated with FB1 to determine its pathological effects on gastric gland and gastric mucosa in the treated mice. For this purpose, the mice were randomly assigned into two groups, namely, control (n?=?14) and treatment (n?=?15). The treatment group was fed with prepared food containing FB1 (150 mg/kg) for a period of 4 months. One day after the last treatment, all animals in both groups were euthanized and their stomach were sampled and prepared for microscopic analysis. Histopathological analysis revealed a significant decrease in parietal cell number and a significant increase in the number of inflammatory cells in gastric mucosa. Also, atrophy of gastric glands was observed. The study confirmed that FB1 poisoning can have toxicopathological effects such as gastric gland atrophy and gastritis on mice gastric tissue.     

Safety of ESWL in elderly: Evaluation of independent predictors and comorbidity on stone‐free rate and complications

Aim: Urinary stone disease affects people of all ages. With its satisfactory efficacy ranges in all age groups and lack of side‐effects, extracorporeal shock wave lithotripsy (ESWL) has become the preferred treatment modality for uncomplicated renal and proximal calculi ≤20 mm. In the present study, we aimed to assess the safety and efficacy of the ESWL treatment in elderly patients. Methods: A retrospective study was carried out on patients aged over 65 years who underwent shock wave lithotripsy at our Department from 2009 to 2011, with a Siemens Lithostar electromagnetic shockwave lithotripter. A total of 231 patients (157 males, 74 females) out of 1694 (13.6%) were studied. The patients were divided into two groups (group 1 = 65–70; group 2 >70). The effect of age and other possible predicting factors (sex, stone localization and stone size) were investigated. Concomitant diseases and related complications were also evaluated. Results: An overall stone‐free rate (SFR) of 82.2% was found. The influence of sex on SFR was non‐significant. There was no significant difference when comparing SFR between the age groups. When patients were divided into those with renal and ureteral stones, the SFR were 94.4% and 67.6% (P < 0.01), respectively. The SFR of the stone size groups, ≤10 mm and >10 mm were 80% and 84.4%, respectively. Comorbidity was present in 148 patients. Complications were noted in 56 of 231 patients. Of 56 patients, 43 had minor complications and 13 major complications. Conclusion: ESWL seems to be an effective first‐line treatment choice for urinary stones in elderly patients with careful patient selection and personalized preparation. Geriatr Gerontol Int 2012; 12: 413–417.     

Tri-layered elastomeric scaffolds for engineering heart valve leaflets

Tissue engineered heart valves (TEHVs) that can grow and remodel have the potential to serve as permanent replacements of the current non-viable prosthetic valves particularly for pediatric patients. A major challenge in designing functional TEHVs is to mimic both structural and anisotropic mechanical characteristics of the native valve leaflets. To establish a more biomimetic model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning and microfabrication techniques. These constructs were fabricated by assembling microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone) (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic mechanical properties similar to the mechanical characteristics of the native heart valves. The engineered scaffolds supported the growth of valvular interstitial cells (VICs) and mesenchymal stem cells (MSCs) within the 3D structure and promoted the deposition of heart valve extracellular matrix (ECM). MSCs were also organized and aligned along the anisotropic axes of the engineered tri-layered scaffolds. In addition, the fabricated constructs opened and closed properly in an ex vivo model of porcine heart valve leaflet tissue replacement. The engineered tri-layered scaffolds have the potential for successful translation towards TEHV replacements.     

Silica vesicles as nanocarriers and adjuvants for generating both antibody and T-cell mediated immune resposes to Bovine Viral Diarrhoea Virus E2 protein

Bovine Viral Diarrhoea Virus (BVDV) is widely distributed in cattle industries and causes significant economic losses worldwide annually. A limiting factor in the development of subunit vaccines for BVDV is the need to elicit both antibody and T-cell-mediated immunity as well as addressing the toxicity of adjuvants. In this study, we have prepared novel silica vesicles (SV) as the new generation antigen carriers and adjuvants. With small particle size of 50 nm, thin wall (∼6 nm), large cavity (∼40 nm) and large entrance size (5.9 nm for SV-100 and 16 nm for SV-140), the SV showed high loading capacity (∼ 250 μg/mg) and controlled release of codon-optimised E2 (oE2) protein, a major immunogenic determinant of BVDV. The in vivo functionality of the system was validated in mice immunisation trials comparing oE2 plus Quil A (50 μg of oE2 plus 10 μg of Quil A, a conventional adjuvant) to the oE2/SV-140 (50 μg of oE2 adsorbed to 250 μg of SV-140) or oE2/SV-140 together with 10 μg of Quil A. Compared to the oE2 plus Quil A, which generated BVDV specific antibody responses at a titre of 10⁴, the oE2/SV-140 group induced a 10 times higher antibody response. In addition, the cell-mediated response, which is essential to recognise and eliminate the invading pathogens, was also found to be higher [1954-2628 spot forming units (SFU)/million cells] in mice immunised with oE2/SV-140 in comparison to oE2 plus Quil A (512–1369 SFU/million cells). Our study has demonstrated that SV can be used as the next-generation nanocarriers and adjuvants for enhanced veterinary vaccine delivery.     

Autologous cartilage grafts enhanced by a novel transplant medium using fibrin sealant and fibroblast growth factor

OBJECTIVE: To introduce and assess a system for the delivery of fibroblast growth factor to autologous cartilage grafts using fibrin sealant and analyze whether this "enhancement" results in reduced rates of cartilage resorption and greater preservation of normal architectural features compared with "unenhanced" cartilage grafts. METHODS: Auricular cartilage segments measuring 1 cm(2) were harvested from 12 New Zealand white rabbits, morselized, and implanted into the subcutaneous dorsum of the upper back for 3 months. The conditions included (1) cartilage alone; (2) cartilage + fibrin sealant; (3/4) cartilage + acidic or basic fibroblast growth factor (aFGF or bFGF); and (5/6) cartilage + fibrin sealant + aFGF or bFGF. Subsequent to graft harvest, gross and microscopic assessments were performed to assess size, structural integrity, and architectural features, with comparisons performed between each of the conditions. RESULTS: The mean areas of the harvested cartilage grafts treated with fibrin sealant + aFGF or bFGF were 1.23 cm(2) and 1.19 cm(2), respectively, while the corresponding value for the untreated (ie, cartilage alone) specimens was 1.03 cm(2). The percentage of decrease in size was 45% for the untreated specimens and 0% for the specimens treated with fibrin sealant + aFGF or fibrin sealant + bFGF. Cartilage treated with fibrin sealant + bFGF had the greatest quantity of elastin fibers of the 6 conditions. Cartilage grafts treated with fibrin sealant alone demonstrated the most intense ground substance staining on a computerized measure of pixel intensity. CONCLUSIONS: Our findings demonstrated significant improvements in graft quality using fibroblast growth factor and fibrin sealant or even fibrin sealant alone. These findings may justify changes in how cartilage grafts are prepared and delivered for facial augmentation procedures to reduce graft resorption and maintain the structural integrity of the cartilage. Further trials will be performed to elucidate the optimal growth factor concentrations for maximum structural and architectural benefits.     

Sudden unexpected death in childhood associated with cardiac rhabdomyoma, involuting adrenal ganglioneuroma, and megalencephaly: another expression of tuberous sclerosis?

We report a 9-year-old, previously healthy girl who died suddenly and unexpectedly and was found at postmortem examination to have a cardiac rhabdomyoma, megalencephaly, and an involuting adrenal ganglioneuroma. Her death was possibly caused by a fatal cardiac arrhythmia resulting from interference of the ventricular septal rhabdomyoma with the cardiac conduction fibers. Her extended family history included a variety of disorders, including cleft lip and palate and ill-defined cardiac and neurologic diseases. The constellation of her autopsy findings suggested a diagnosis of tuberous sclerosis, for which there are gene defects that can be identified in surviving family members.