Mechanical properties of native and decellularized aortic wall after long-term storage in biocide solutions

Objective: to determine the optimal method for long-term wet storage of donor material (50 days after collection), with maximum ability to preserve the original mechanical characteristics.Materials and methods. Porcine aortic wall fragments were used as objects of study. Half of the original material underwent detergent-based decellularization. The entire material (native and processed) was placed for 50 days in biocidal solutions: complex alcohol solution; ethanol and glycerol mixture; antibiotics mixture. Then the tests for mechanical strength of native and decellularized samples were carried out by the method of uniaxial longitudinal and circumferential stress.Results. Storage of native material in all media resulted in a significant increase in tensile strength. In the «complex alcohol solution», «ethanol and glycerol mixture», and «antibiotic mixture» group, tensile strength increased by 1.38-, 1.72- and 1.62-fold compared to the native control in circumferential tension. Also, in the «complex alcohol solution» group, the decellularized material was 1.57-fold stronger than the native in circumferential tension. In the «antibiotic mixture» group, the decellularized material was 1.33-fold less strong than the native in longitudinal tension. According to elongation to rupture data, significantly greater plasticity was noted in the «ethanol-glycerol» storage group for the decellularized aortic wall compared to the control group (1.5-fold). Young’s modulus did not reliably differ from those of control in all experimental groups regardless of the stress direction. Notably, decellularized specimens clearly tended to be stiffer under circumferential stress.Conclusion. Detergent-based decellularization of the porcine aortic wall and subsequent storage of these samples in our chosen experimental solutions for 50 days does not significantly affect the elastic properties of the material. Our proposed treatment methods partially increase the stiffness of the material after storage in alcohol-containing solutions.

The efficacy and safety of citrate mixture vs sodium bicarbonate on urine alkalization in Chinese primary gout patients with benzbromarone: a prospective, randomized controlled study

Objectives To compare the efficacy and safety of citrate mixture and sodium bicarbonate on urine alkalization in gout patients under benzbromarone treatment. Methods A prospective, randomized, parallel controlled trial was conducted among 200 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. The participants were randomly divided into two groups (1:1), sodium bicarbonate group (3 g/day) and citrate mixture group (7 g/day). All patients were prescribed with 25 mg/day benzbromarone at initiation and maintained at a dose of 50 mg/day. Clinical and biochemical data were collected at each follow-up time point (baseline, weeks 2, 4, 8 and 12). Results A total of 182 patients completed the 12-week urine alkalization study. The urine pH value of both groups increased significantly from the baseline to the final follow-up time point (sodium bicarbonate group, 5.50–6.00, P < 0.05; citrate mixture group, 5.53–5.93, P < 0.05). While the comparisons regarding urine pH between treatment groups showed no significant differences for each time point. The estimated glomerular filtration rate (eGFR) dropped significantly after 12 weeks’ trial in the sodium bicarbonate group (P < 0.01), while it was comparable between baseline and the last follow-up (P > 0.05) in the citrate mixture group. Results of urine analysis showed that the incident rate of occult blood in the sodium bicarbonate group was higher than that in the citrate mixture group (38 vs 24%, P < 0.05), accompanied by a similar occurrence of kidney stones. After 12-week follow-up, the frequency of twice gout flare in the citrate mixture group was significantly lower than that in sodium bicarbonate group (4 vs 12%, P = 0.037). No treatment-emergent adverse events occurred. Conclusion The efficacy of citrate mixture on urine alkalization is comparable to sodium bicarbonate under benzbromarone treatment without significant adverse events. Citrate mixture is superior to sodium bicarbonate in lowering the incidence of urine occult blood and the frequency of gout attacks. Trial registration Registered with ChiCTR (http://www.chictr.org.cn), No. ChiCTR1800018518.

A phase II randomized clinical trial and mechanistic studies using improved probiotics to prevent oral mucositis induced by concurrent radiotherapy and chemotherapy in nasopharyngeal carcinoma.

e18568 Background: Earlier evidence has proven that probiotic supplements can reduce radiochemotherapy (CCRT) -induced oral mucositis (OM) in nasopharyngeal cancer (NPC). We have recently modified the ingredient of the probiotics by combining Bifidobacterium animalis, Lactobacillus plantarum, Lactobacillus rhamnosus and Lactobacillus acidophilus. This report includes the Phase II clinical trial to evaluate the effect of the modified probiotics along with mechanistic studies. Methods: We enrolled 85 patients with locally advanced NPC who were undergoing CCRT. The patients were randomized (1:1) to receive either probiotic mixture or placebo. The incidence of severe OM (grade 3 or higher) was the primary endpoint to document. We utilized a rat model. We collected rat’s samples from the tongue, blood and fecal and proximal colon tissues on a various days following treatment and tested for the mechanism of probiotics mixture on OM. Results: We found that patients taking the probiotic mixture showed significantly reduced OM. The incidences for Grade 0, 1, 2, 3 and 4 OM in the placebo group and the probiotic mixture group were 0%, 14.7%, 38.2%, 32.4%, and 14.7% and 13.9%, 36.1%, 25%, 22.2%, and 2.8%, respectively. Furthermore, patients in the probiotic mixture group showed lower reduction rate in CD3+ T cells (75.5% vs 81%, P < 0.01), CD4+ T cells (64.53% vs 79.53%, P < 0.01), and CD8+ T cells (75.59% vs 62.36%, P < 0.01) compared with the placebo group. In the rat model, the control group rats showed more severe mucositis, increased histologic changes of the oral mucosa on the 7th, 14th and 21th day, with the 14th day most significant. CCRT also caused an enhanced inflammation response and cell apoptosis in tongue in the control group. Moreover, CCRT increased the intestinal permeability through reducing the zonula occludens-1(ZO-1) and Claudin-1 expression in colon tissues and increasing the inflammation factors in bloods. The structure of gut microbiota was also disturbed in the control group mainly with the increasing abundance of Bacteroidetes and decreasing abundance of Firmicutes. However, probiotics mixture ameliorated the severity of OM, decreased the inflammation response, cell apoptosis, intestinal permeability, and restored the structure of gut microbiota to normal. Conclusions: The modified probiotic mixture significantly reduces the severity of OM through enhancing the immune response of patients and modifying structure of gut microbiota. Clinical trial information: NCT03112837.

Treatment efficacy of tolterodine versus belladonna mixture in children with idiopathic overactive bladder

ObjectivesChildren with symptoms of urinary urgency, frequency and incontinence are common in the clinic. The aim of the present study was to compare the tolerability and efficacy of tolterodine, a bladder-selective muscarinic receptor antagonist, with belladonna mixture, a traditional anticholinergic drug, in the treatment of idiopathic overactive bladder in children.MethodsChildren aged 5–10 years with a history of diurnal urgency, frequency and incontinence were randomly divided into two groups. Participants in group 1 were given tolterodine 1 mg twice a day for 14 days. If the results were found to be mildly ineffective, after the first 14 days of therapy, prolonged course with 2 mg twice a day was given. In group 2, the children were treated with belladonna mixture 5 mL twice a day for 14 days. Anticholinergic side effects were recorded during the therapy and efficacy was evaluated with voiding diary recorded by the parents at the beginning and end of therapy.ResultsA total of 668 cases were included in this study and 334 for each 25 group (496 boys and 172 girls). Evident anticholinergic side effects which could cease the therapy, such as dry mouth, constipation, mood changes, irritability, and so on, exhibited only on 2% of participants in the tolterodine group but 69% in the belladonna mixture group (p≤0.05). The symptoms of detrusor overactivity disappeared or significantly improved in 80% of children in the tolterodine group and 37% in the belladonna mixture (p≤0.05) group.ConclusionsTolterodine had better tolerability and efficacy than belladonna mixture in treating overactive bladder in children.

Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney

Background: Cadmium and lead are widespread and non-biodegradable pollutants of great concern to human health. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and it is therefore of paramount importance to assess their toxicity. In this study, we investigated the toxicity of Cd and Pb alone and as a mixture in an animal model of acute exposure. Methods: Experimental groups received a single treatment of aqueous solution of Cd-chloride (15 and 30 mg/kg body weight (b.w.) and Pb-acetate (150 mg/kg b.w.), while the mixture group received 15 mg Cd/kg b.w. and 150 mg Pb/kg b.w. Toxic effects of individual metals and their mixture were investigated on hematological and biochemical parameters, and the redox status in the plasma, liver, and kidneys of treated Wistar rats. Results: Tissue-specific changes were recorded in various parameters of oxidative damage, while the accumulation of metals in tissues accompanied the disturbances of both hematological and biochemical parameters. It was observed that the level of toxic metals in tissues had a different distribution pattern after mixture and single exposure. Conclusions: Comprehensive observations suggest that exposure to Cd and Pb mixtures produces more pronounced effects compared to the response observed after exposure to single metal solutions. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic metals in the organisms.

Effect of Proparacaine 0.375%-Sodium Fluorescein 0.25% Eye Drop Mixture and Fluorescein Strip on Anterior Segment Parameters

Purpose. To determine the effect of proparacaine 0.375%-sodium fluorescein 0.25% eye drop mixture and fluorescein strip on anterior segment parameters commonly used in routine ophthalmology practice. Methods. 115 healthy volunteers without any systemic or ocular disease were divided into two groups. 57 volunteers were in the proparacaine 0.375%-sodium fluorescein 0.25% eye drop mixture group, and 58 volunteers were in the fluorescein strip group. Measurements (CCT (central corneal thickness), topographic pupil diameter, AD (aqueous depth), ACV (anterior chamber volume), ICA (iridocorneal angle), LLD (limbus-limbus distance), and CV (corneal volume)) were taken before and at 1, 5, 15, and 30 minutes after application. Results. 59 (51.3%) participants were female, and 56 (48.7%) were male. The mean age of the drop application group was 26.88 ± 8.03, and the mean age of the strip application group was 26.33 ± 7.28. The mean CCT was 556 ± 32 μm before drop application and 569 ± 30 μm in the 1st minute, 560 ± 32 μm in the 5th minute, and 559 ± 31 μm in the 15th minute. The change was statistically significant (p<0.001, p=0.005, and p=0.013, resp.). Before the strip application, mean CCT was 552 ± 36 μm, while it increased to 556 ± 36 μm at the 1st minute, and this change was statistically significant (p=0.002). The mean CV before dropping was 59.29 ± 3.53 mm3 and 60.62 ± 3.53 mm3 at the 1st minute and 59.66 ± 3.70 mm3 at the 5th minute, which was statistically significant (p<0.001 and p=0.034). Mean topographic pupil diameters at the 1st, 5th, 15th, and 30th minute after application of drops and strips were not significantly changed compared to the preapplication values in the AD, ACV, ICA, and LLD measurements. Conclusions. Proparacaine 0.375%-sodium fluorescein 0.25% eye drop mixture and fluorescein strip application lead to a temporary change in CCT and CV of the anterior segment parameters. Anterior segment measurements with the Scheimpflug camera have to be done before topical fluorescein application.

SYNERGISTIC EFFECT OF GINGER, PROPOLIS ADDED TO CONCENTRATED DIET ON SOME PRODUCTION AND PHYSIOLOGICAL CHARACTERISTICS OF THE AWASSI EWES

This study was aimed to find out the synergistic effect of ginger and propolis some productivity and physiological traits of Awassi ewes. The study was conducted in field the Department of Animal Production - College of Agriculture, University of Baghdad Al-Jaderia, during 14/01/2016 - 03/27/2016, using 12 Awassi ewes with ages from 9 -11 months old ,average weight of 31 kg, The results showed a significant increase in the glucose for concentration (P <0. 05) in the ginger group compared with other groups where .significant increase in the concentration of blood sugar(81.0 mg / 100 ml of blood) in the first month and continued to the second month,The level of cholesterol increase (65.90) in the second month of the group of ginger, triglycerides, Low-density lipid had significant increase in the group ginger , significant increase in propolis group with high density lipid (54.00) , total protein , albumin and GPT enzyme shows significant increased effect on the contrary GOT enzyme was increased significant in mixture group in the second month (13.00IU / liter), while the level of hemoglobin and the Packed cells volume and the total count of white blood cells and red blood cells did not show any significant differences(normal value ) , It can be conclude from this study that the addition of 25 g ginger to concentrated diet / head / day is the best treatment.

Lutein, zeaxanthin and meso-zeaxanthin content of eggs laid by hens supplemented with free and esterified xanthophylls

The xanthophyll carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) are found at the macula, the central part of the retina, where they are referred to as macular pigment (MP). MP is studied in human subjects because of its proven role in enhancing visual function and its putative role in protecting against age-related macular degeneration. These benefits are probably due to the antioxidant and short-wavelength filtering properties of MP. It is known that eggs are a dietary source of L and Z. This experiment was designed to measure the egg yolk carotenoid response to hen supplementation with L, Z and MZ. A total of forty hens were used in the trial and were divided into eight groups of five hens. Each group was supplemented (with about 140 mg active xanthophylls/kg feed) with one of the following oil-based carotenoid formulations for 6 weeks: unesterified L (group 1); L diacetate (group 2); unesterified Z (group 3); Z diacetate (group 4); unesterified MZ (group 5); MZ diacetate (group 6); L–MZ (1:1) diacetate mixture (group 7); L–MZ diacetate (1:3) mixture (group 8). Yolk carotenoid content was analysed weekly (in four randomly selected eggs) by HPLC. We found that hens supplemented with Z diacetate and MZ diacetate produced eggs with significantly greater carotenoid concentrations than their free form counterparts. This finding potentially represents the development of a novel food, suitable to increase MP and its constituent carotenoids in serum.

Overcoming Allelic Specificity by Immunization with Five Allelic Forms of Plasmodium falciparum Apical Membrane Antigen 1

ABSTRACTApical membrane antigen 1 (AMA1) is a leading vaccine candidate, but the allelic polymorphism is a stumbling block for vaccine development. We previously showed that a global set of AMA1 haplotypes could be grouped into six genetic populations. Using this information, six recombinant AMA1 proteins representing each population were produced. Rabbits were immunized with either a single recombinant AMA1 protein or mixtures of recombinant AMA1 proteins (mixtures of 4, 5, or 6 AMA1 proteins). Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), and purified IgG from each rabbit was used for growth inhibition assay (GIA) with 12 different clones of parasites (a total of 108 immunogen-parasite combinations). Levels of antibodies to all six AMA1 proteins were similar when the antibodies were tested against homologous antigens. When the percent inhibitions in GIA were plotted against the number of ELISA units measured with homologous AMA1, all data points followed a sigmoid curve, regardless of the immunogen. In homologous combinations, there were no differences in the percent inhibition between the single-allele and allele mixture groups. However, all allele mixture groups showed significantly higher percent inhibition than the single-allele groups in heterologous combinations. The 5-allele-mixture group showed significantly higher inhibition to heterologous parasites than the 4-allele-mixture group. On the other hand, there was no difference between the 5- and 6-allele-mixture groups. These data indicate that mixtures with a limited number of alleles may cover a majority of the parasite population. In addition, using the data from 72 immunogen-parasite combinations, we mathematically identified 13 amino acid polymorphic sites which significantly impact GIA activities. These results could be a foundation for the rational design of a future AMA1 vaccine.