Marine and Agro-Industrial By-Products Valorization Intended for Topical Formulations in Wound Healing Applications

Over the past years, research attention has been focusing more on waste-derived, naturally derived, and renewable materials, in the view of a more sustainable economy. In this work, different topical formulations were obtained from the valorization of marine and agro-industrial by-products and the use of Carbopol 940 as gelling agent. In particular, the combination of extracts obtained from the marine snail, Rapanosa venosa, with Cladophora vagabunda and grape pomace extracts, was investigated for wound healing purposes. Rapana venosa has demonstrated wound healing properties and antioxidant activity. Similarly, grape pomace extracts have been shown to accelerate the healing process. However, their synergic use has not been explored yet. To this aim, four different formulations were produced. Three formulations differed for the presence of a different extract of Rapana venosa: marine collagen, marine gelatin, and collagen hydrolysate, while another formulation used mammalian gelatin as further control. Physico-chemical properties of the extracts as well as of the formulations were analyzed. Furthermore, thermal stability was evaluated by thermogravimetric analysis. Antioxidant capacity and biological behavior, in terms of cytocompatibility, wound healing, and antimicrobial potential, were assessed. The results highlighted for all the formulations (i) a good conservation and thermal stability in time, (ii) a neutralizing activity against free radicals, (iii) and high degree of cytocompatibility and tissue regeneration potential. In particular, collagen, gelatin, and collagen hydrolysate obtained from the Rapana venosa marine snail represent an important, valuable alternative to mammalian products.     

New alternatives for erythropoietin therapy in chronic renal failure

Erythropoietin (EPO) is one of the main cytokines involved in the regulation of erythropoiesis. The main site of EPO production are the kidneys. An altered EPO production leads to pathological conditions such as anemia and polycythaemia. Due to the progressive loss of renal peritubular cells, patients with chronic kidney disease (CKD) have low EPO plasma levels. This decreases erythron stimulation with the direct consequence of developing anemia. Before the introduction in the clinical practice of rHuEpo, in the late 1980s, the only solution for treating this type of anemia were blood transfusions and anabolic steroids. Even rHuEpo has proven to be safe and effective for treatment of anemias, there are some concerns about its cost, the need for frequent parenteral administration, and development of anti-EPO antibodies. These inconveniences prompted the search for novel erythropoiesis stimulating agents. Different strategies lead to isolation or chemical synthesis of such agents as darbepoetin alfa and EPO mimetics. In this review, we present some general aspects of EPO biology, with emphasis on chronic renal failure, and expose some of the alternatives to EPO used for anemia correction.     

Pharmacokinetics and comparative bioavailability of two vinpocetine tablet formulations in healthy volunteers by using the metabolite apovincaminic acid as pharmacokinetic parameter

The objective of this study was to evaluate the pharmacokinetics of apovincaminic acid, the main metabolite of vinpocetine ((3alpha, 16alpha) -eburnamenine-14-carboxylic acid ethyl ester, CAS 42971-09-5), and to assess the average bioequivalence of two immediate release formulations of 10 mg vinpocetine tablets in 24 healthy male volunteers. The relative bioavailability of the test (generic) product (Vimpocetina) with respect to the reference product was determined in a single dose, randomized, crossover study. A simple, rapid specific and reliable high performance liquid chromatographic method coupled with mass spectrometry detection has been developed and validated for vinpocetine and apovincaminic acid. However, only the concentrations of the metabolite could be used for bioequivalence determinations because the concentrations of the parent drug were too low to be accurately measured in the biological matrix. The compartmental analysis of the metabolite's appearance-disappearance in blood shows similarity with first-order kinetics of a drug extravascularly administered. The apparent pharmacokinetic constants were determined. The mean values for the Cmax were 49.5 (+/- 16) ng/ml for test and 51.4 (+/- 14) ng/ml for the reference product. The mean values for the AUC0-infinity were 95 (+/- 29) ng/ml x h for test and 96.9 (+/- 26) ng/ml x h for reference, respectively. The 90 % confidence intervals for test/reference mean ratios of the plasma pharmacokinetic variables Cmax and AUC0-infinity lie between 0.83-1.08 and 0.88-1.08, respectively, which is within the conventional bioequivalence range of 80-125 % (Schuirman test). The difference between Tmax of the test and reference products was statistically non-significant (Friedman test). The test product is therefore bioequivalent to the reference product with respect to the rate and extent of apovincaminic acid pharmacokinetics.     

Value of the intraoperative assessment of the depth of myometrial invasion in endometrial carcinoma

OBJECTIVES: The aim of the study was to evaluate the value of intraoperative assessment of depth of myometrial invasion in patients with FIGO stage I of the endometrial carcinoma. MATERIAL AND METHODS: A total number of 112 patients with FIGO stage I of the endometrial carcinoma undergoing surgery were enrolled in the study. All patients had undergone intraoperative assessment of the depth of myometrial invasion performed by a surgeon. The depth was determined as more or less than 50% of myometrial thickness according to FIGO classification. Gross visual estimation of the depth of myometrial invasion at the time of the operation was compared with the final histopathological report. Sensitivity, specificity and positive and negative predictive values of the method were determined by means of statistical analyses. RESULTS: The depth of the myometrial invasion was accurately determined by the surgeon in 82.1% of cases. Sensitivity and specificity were 68% and 82.1%, respectively. The accurate prediction rate of the myometrial invasion in the group of patients with well differentiated (G1) endometrial carcinoma was higher (88.4%) than in group with moderately and low differentiated tumour (78.3%). CONCLUSIONS: The accuracy of macroscopic evaluation of myometrial invasion is high and reaches up to 82.1%. The accurate determination rate increases if the differentiation of tumour is higher.     

Hydroxyapatite from Natural Sources for Medical Applications

The aim of this work is to study the physical-chemical, mechanical, and biocompatible properties of hydroxyapatite obtained by hydrothermal synthesis, at relatively low temperatures and high pressures, starting from natural sources (Rapana whelk shells), knowing that these properties influence the behavior of nanostructured materials in cells or tissues. Thus, hydroxyapatite nanopowders were characterized by chemical analysis, Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In vitro studies on osteoblast cell lines (cytotoxicity and cell proliferation), as well as preliminary mechanical tests, have been performed. The results showed that the obtained powders have a crystallite size below 50 nm and particle size less than 100 nm, demonstrating that hydrothermal synthesis led to hydroxyapatite nanocrystalline powders, with a Ca:P ratio close to the stoichiometric ratio and a controlled morphology (spherical particle aggregates). The tensile strength of HAp samples sintered at 1100 °C/90 min varies between 37.6–39.1 N/mm². HAp samples sintered at 1300 °C/120 min provide better results for the investigated mechanical properties. The coefficient of friction has an appropriate value for biomechanical applications. The results of cell viability showed that the cytotoxic effect is low for all tested samples. Better cell proliferation is observed for osteoblasts grown on square samples.     

Magnesium—A Potential Key Player in Inflammatory Bowel Diseases?

The altered magnesium status in inflammatory bowel disease (IBD) patients may have a significant clinical imprint considering its role in cell signaling and genomic stability, as well as its involvement in IBD patients’ fatigue. Our study pioneers the investigation of magnesium hair concentration patterns in an adult population of IBD patients. The hair magnesium concentration in IBD patients is compared to healthy controls in order to identify correlations between the magnesium status and relevant parameters related to disease activity, psychological status, and sleep quality. We report a significantly lower hair magnesium concentration within the IBD group compared to healthy controls (95%CI: 0.006–0.062; p = 0.017) and lower levels in CD compared to UC (95%CI: −0.061–−0.002; p = 0.038). We identified a borderline statistical significance between the hair magnesium concentration and UC disease activity (95%CI; −0.679–0.008; p = 0.055) and a significantly lower magnesium concentration in patients who reported increased sleep latency (95%CI −0.65–−0.102; p = 0.011) or decreased sleep duration (95%CI −0.613–−0.041; p = 0.028). Our results advance several hypotheses with substantial clinical impact to be confirmed in future studies. Magnesium levels appear to be modified in IBD patients, which suggests it either plays a primary role in disease pathophysiology or a is result of the disease’s evolution. Magnesium could be used in predictive models for clinical/subclinical disease activity. Moreover, magnesium supplementation may improve IBD evolution and sleep quality for patients with a deficit of this mineral. However, confirmatory evidence-based studies are needed to generate specific dosing, time of supplementation, and optimum monitoring of magnesium status in IBD patients.     

Static and Fatigue Behaviour of Double-Lap Adhesive Joints and Notched Metal Samples Reinforced by Composite Overlays

The use of composite overlays to increase the fatigue life of notched steel samples is discussed in this paper. For such purposes, in the first set of studies, static and fatigue tests as well as the detailed analytical and numerical analyses for samples with double-lap joints were performed. Based on such studies, the shapes of the composite overlays were set. For a better understanding of the failure forms of the investigated adhesive joints, the experimental studies were monitored with the use of digital image correlation. In the second set of experimental studies, the static and fatigue tensile tests were performed for steel samples with a rectangular opening with rounded corners reinforced by composite overlays. The different shapes (square 45 × 45 mm and long stripes 180 × 15 mm) and composite materials (GFRP and CFRP) were used as overlays. The obtained improvement of fatigue life was in the range of 180–270% in the case of the rectangular overlays and 710% in the case of application of the overlays in the form of the long stripes. This was also confirmed by numerical analyses in which a reduction in the stress concentration factor from 2.508 (bare sample) through 2.014–2.183 (square 45 × 45 mm overlays) to 1.366 (overlays in the form of long stripes 180 × 15 mm) was observed.     

A summary-statistics-based approach to examine the role of serotonin transporter promoter tandem repeat polymorphism in psychiatric phenotypes

In genetic studies of psychiatric disorders in the pre-genome-wide association study (GWAS) era, one of the most commonly studied loci is the serotonin transporter (SLC6A4) promoter polymorphism, a 43-base-pair insertion/deletion polymorphism in the promoter region (5-HTTLPR). The genetic association signals between 5-HTTLPR and psychiatric phenotypes, however, have been inconsistent across many studies. Since the polymorphism cannot be tested via available SNP arrays, we had previously proposed an efficient machine learning algorithm to predict the genotypes of 5-HTTLPR based on the genotypes of eight nearby SNPs, which requires access to individual-level genotype and phenotype data. To utilize the advantage of publicly available GWAS summary statistics obtained from studies with very large sample sizes, we develop a GWAS summary-statistics-based approach for testing the variable number of tandem repeat (VNTR) associations with various phenotypes. We first cross-verify the accuracy of the summary-statistics-based approach for 61 phenotypes in the UK Biobank. Since we observed a strong similarity between the predicted individual-level 5-HTTLPR genotype-based approach and the summary-statistics-based approach, we applied our method to the available neurobehavioral GWAS summary statistics data obtained from large-scale GWAS. We found no genome-wide significant evidence for association between 5-HTTLPR and any of the neurobehavioral traits. We did observe, however, genome-wide significant evidence for association between this locus and human adult height, BMI, and total cholesterol. Our summary-statistics-based approach provides a systematic way to examine the role of VNTRs and related types of genetic polymorphisms in disease risk and trait susceptibility of phenotypes for which large-scale GWAS summary statistics data are available.Subject terms: Behavioural genetics, Genetic association study     

A three-dimensional evaluation of microleakage of class V cavities prepared by the very short pulse mode of the erbium:yttrium–aluminium–garnet laser

The aim of this study was to evaluate microleakage along resin restoration in cavities prepared with an erbium:yttrium–aluminium–garnet (Er:YAG) laser, with and without acid etching, and to compare it with that in diamond-drilled cavities. Thirty intact molars were divided into three equal groups. In the teeth in group I, class V cavities were prepared with a diamond drill. Cavities in groups II and III were prepared with an Er:YAG laser (400 mJ/15 Hz for enamel and 250 mJ/10 Hz for dentine). The cavities in groups I and II were acid-etched and adhesive and flowable composite were applied to all cavities. The specimens were first immersed in dye for 24 h and then in 5% nitric acid for 72 h for softening. The fillings were extracted and photographed through a dissecting microscope. The leakage area was measured with specially designed software. The Kruskal–Wallis test showed that the best ranking was group II [mean range (m.r.) = 27.46], followed by group I (m.r. = 33.48) and, lastly, group III (m.r. = 45.15). The differences between groups I and III (P = 0.023) and between groups II and III were statistically significant (P = 0.080). The least microleakage was found in those cavities prepared by Er:YAG laser and subsequently acid-etched, whereas the most leakage was in the lased cavities that had not been etched; the traditional diamond-drilled acid-etched cavities produced medium leakage.