Preparation and characterization of collagen-based ADSC-carrier sheets for cardiovascular application

The use of scaffolds composed of natural biodegradable matrices represents an attractive strategy to circumvent the lack of cell engraftment, a major limitation of stem cell therapy in cardiovascular diseases. Bovine-derived non-porous collagen scaffolds with different degrees of cross-linking (C0, C2, C5 and C10) were produced and tested for their mechanical behavior, in vitro biocompatibility with adipose-derived stem cells (ADSCs) and tissue adhesion and inflammatory reaction. Uniaxial tensile tests revealed an anisotropic behavior of collagen scaffolds (2 × 0.5 cm) and statistically significant differences in the mechanical behavior between cross-linked and non-cross-linked scaffolds (n = 5). In vitro, ADSCs adhered homogenously and showed a similar degree of proliferation on all four types of scaffolds (cells × 10³ cm^?2 at day 7: C0: 94.7 ± 37.1; C2: 91.7 ± 25.6; C5: 88.2 ± 6.8; C10: 72.8 ± 10.7; P = n.s.; n = 3). In order to test the in vivo biocompatibility, a chronic myocardial infarction model was performed in rats and 1.2 × 1.2 cm size collagen scaffolds implanted onto the heart 1 month post-infarction. Six animals per group were killed 2, 7 and 30 days after transplant. Complete and long-lasting adhesion to the heart was only observed with the non-cross-linked scaffolds with almost total degradation 1 month post-transplantation. After 7 and 30 days post-implantation, the degree of inflammation was significantly lower in the hearts treated with non-cross-linked scaffolds (day 7: C0: 10.2 ± 2.1%; C2: 16.3 ± 2.9%; C5: 15.9 ± 4.8%; C10: 17.4 ± 4.1%; P < 0.05 vs. C0; day 30: C0: 1.3 ± 1.3%; C2: 9.4 ± 3.0%; C5: 7.0 ± 2.1%; C10: 9.8 ± 2.5%; P < 0.01 vs. C0). In view of the results, the non-cross-linked scaffold (C0) was chosen as an ADSC-carrier sheet and tested in vivo. One week post-implantation, 25.3 ± 7.0% of the cells transplanted were detected in those animals receiving the cell-carrier sheet whereas no cells were found in animals receiving cells alone (n = 3 animals/group).We conclude that the biocompatibility and mechanical properties of the non-cross-linked collagen scaffolds make them a useful cell carrier that greatly favors tissue cell engraftment and may be exploited for cell transplantation in models of cardiac disease.     

Complexes leucoplaquettaires en tant que marqueur d’activation dans les concentrés plaquettaires standards

ObjectivesSeveral in vitro laboratory tests to assess the quality control of platelet concentrates (PC) are available. Some of them have a good correlation with the platelet recovery index. To assess the quality control of standard PC prepared in our blood bank, we measured the blood gas and the degree of platelet activation.Materials and methodsSPC were prepared by the PRP method. Fifty-five SPC (45 SPC at day one of storage and 20 SPC at day five of storage) were analysed. Blood gas (pH, PO₂, PCO₂ and bicarbonate concentration) in the SPC were measured by blood gas automate. Platelet activation profile were determined by measuring the percentage of platelet expressing the CD62p (% CD62) and the percentage of platelet-leukocyte aggregate (% PLA).ResultsThe pH values of all studied SPC were comprised between 7.0 and 7.6. SPC at day 1 of storage have a significantly higher pH than those at day 5 of storage (7.5 ± 0.05 versus 7.3 ± 0.14; p < 0.001). The % CD62p were higher in SPC at day five compared to the SCP at day one without reaching a statistical significance (28.4 ± 15% versus 24.3 ± 9.7%, p = 0.052). The percentage of PLA were higher in SPC at day one compared to SCP at day five although this difference is not statistically significant (22.2 ± 7.5% versus 17.9 ± 8.0%; p = 0.23).ConclusionPreparation and storage procedure adopted in our centre did not significantly affect the quality SPC. Our study is the first to assess the PLA in PC. Studies assessing the PLA are warranted to appreciate the clinical impact of this parameter.     

Alpha-mannosidase activity in goats fed with Sida carpinifolia

Human α-mannosidosis results from α-mannosidase deficiency and progressive accumulation of mannose-rich oligosaccharides in lysosomes. Two days before Saanen goats were fed with Sida carpinifolia, α-mannosidase activity in leukocytes was 128±28 nmoles 4-MU/h/mg protein (first trial) and 104±6 nmoles 4-MU/h/mg protein (second trial). At day 5, after the introduction of S. carpinifolia diet, the α-mannosidase activity in leukocytes was significantly increased, both in the first (288±13 nmoles 4-MU/h/mg protein) and in the second trial (303±45 nmoles 4-MU/h/mg protein), and it returned to normal levels 2 days after the withdrawal of the plant from the diet (114±7 nmoles 4-MU/h/mg protein in first trial, and 108±25 nmoles 4-MU/h/mg protein in the second one). Plasma α-mannosidase activity decreased significantly 4 days after animal exposure to the S. carpinifolia diet (769±167 nmoles 4-MU/h/ml) and returned to normal values 10 days after the withdrawal of the plant from the diet (1289±163 nmoles 4-MU/h/ml). Thin-layer chromatography showed an abnormal excretion of oligosaccharides in urine as of day 2 after diet exposure, which persisted until one day after the withdrawal of the plant. Animals presented neurological clinical signs beginning at day 37 (in the first trial) and at day 25 (in the second trial) after being fed with the plant. The results obtained herein suggest that oligosaccharides observed in urine are a result of a decrease in α-mannosidase activity in plasma. S. carpinifolia seems to have other compounds that act on α-mannosidase enzyme in leukocytes in a competitive manner with swainsonine. The increase in α-mannosidase enzyme in leukocytes could be attributed to one of these compounds present in S. carpinifolia.     

Continuous monitoring of electromyography (EMG), mechanomyography (MMG), sonomyography (SMG) and torque output during ramp and step isometric contractions

In this study we simultaneously collected ultrasound images, EMG, MMG from the rectus femoris (RF) muscle and torque signal from the leg extensor muscle group of nine male subjects (mean ± SD, age = 30.7 ± .4.9 years; body weight = 67.0 ± 8.4 kg; height = 170.4 ± 6.9 cm) during step, ramp increasing, and decreasing at three different rates (50%, 25% and 17% MVC/s). The muscle architectural parameters extracted from ultrasound imaging, which reflect muscle contractions, were defined as sonomyography (SMG) in this study. The cross-sectional area (CSA) and aspect ratio between muscle width and thickness (width/thickness) were extracted from ultrasound images. The results showed that the CSA of RF muscles decreased by 7.25 ± 4.07% when muscle torque output changed from 0% to 90% MVC, and the aspect ratio decreased by 41.66 ± 7.96%. The muscle contraction level and SMG data were strongly correlated (R² = 0.961, P = 0.003, for CSA and R² = 0.999, P < 0.001, for width/thickness ratio). The data indicated a significant difference (P < 0.05) in percentage changes for CSA and aspect ratio among step, ramp increasing, and decreasing contractions. The normalized EMG RMS in ramp increasing was 8.25 ± 4.00% higher than step (P = 0.002). The normalized MMG RMS of step contraction was significantly lower than ramp increasing and decreasing, with averaged differences of 12.22 ± 3.37% (P = 0.001) and 12.06 ± 3.37% (P = 0.001), respectively. The results of this study demonstrated that the CSA and aspect ratio, i.e., SMG signals, can provide useful information about muscle contractions. They may therefore complement EMG and MMG for studying muscle activation strategies under different conditions.     

Mesenchymal stem cell proliferation and differentiation on an injectable calcium phosphate – Chitosan composite scaffold

Calcium phosphate cement (CPC) can be molded or injected to form a scaffold in situ, has excellent osteoconductivity, and can be resorbed and replaced by new bone. However, its low strength limits CPC to non-stress-bearing repairs. Chitosan could be used to reinforce CPC, but mesenchymal stem cell (MSC) interactions with CPC-chitosan scaffold have not been examined. The objective of this study was to investigate MSC proliferation and osteogenic differentiation on high-strength CPC-chitosan scaffold. MSCs were harvested from rat bone marrow. At CPC powder/liquid (P/L) mass ratio of 2, flexural strength (mean ± sd; n = 5) was (10.0 ± 1.1) MPa for CPC-chitosan, higher than (3.7 ± 0.6) MPa for CPC (p < 0.05). At P/L of 3, strength was (15.7 ± 1.7) MPa for CPC-chitosan, higher than (10.2 ± 1.8) MPa for CPC (p < 0.05). Percentage of live MSCs attaching to scaffolds increased from 85% at 1 day to 99% at 14 days. There were (180 ± 37) cells/mm² on scaffold at 1 day; cells proliferated to (1808 ± 317) cells/mm² at 14 days. SEM showed MSCs with healthy spreading and anchored on nano-apatite crystals via cytoplasmic processes. Alkaline phosphatase activity (ALP) was (557 ± 171) (pNPP mM/min)/(μg DNA) for MSCs on CPC-chitosan, higher than (159 ± 47) on CPC (p < 0.05). Both were higher than (35 ± 32) of baseline ALP for undifferentiated MSCs on tissue-culture plastic (p < 0.05). In summary, CPC-chitosan scaffold had higher strength than CPC. MSC proliferation on CPC-chitosan matched that of the FDA-approved CPC control. MSCs on the scaffolds differentiated down the osteogenic lineage and expressed high levels of bone marker ALP. Hence, the stronger CPC-chitosan scaffold may be useful for stem cell-based bone regeneration in moderate load-bearing maxillofacial and orthopedic applications.     

Bone mineral density in pediatric survivors of Hodgkin and non-Hodgkin lymphomas

PurposeTo assess skeletal mass in survivors of childhood Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) 1–5 years after treatment, and to identify potential risk factors influencing bone mineral density (BMD).Patients/methodsThis cross-sectional study was conducted in a cohort of 43 survivors (HD = 31; NHL = 12); mean age: 16.21 ± 4.4. Total body bone mineral content (TBMC) and density (TBBMD), and lumbar spine density (LSBMD) were determined using dual-energy X-ray absorptiometry.ResultsThree of all 43 patients developed low BMD. No significant differences in height, weight, and/or BMD Z-scores were found between HD and NHL survivors, children who received and did not receive radiotherapy, and the groups with different chemotherapeutic blocks. No differences were noted between the Z-scores of BMC (mean ± SD: 0.31 ± 1.29 vs. −0.089 ± 0.61, p = 0.165), TBBMD (mean ± SD: −0.32 ± 1.21 vs. −0.27 ± 0.91, p = 0.76), or the LSBMD (mean ± SD: −0.183 ± 1.54 vs. −0.17 ± 0.87, p = 0.637) in subgroups, in accordance with time after therapy (subgroup I < 2 years and subgroup II > 2 years after treatment). In HD survivors, age at diagnosis only affected the TBBMD Z-score (a decrease of 0.127 in total BMD Z-score per each year, R² = 0.999, p < 0.001).ConclusionsChildhood lymphoma survivors demonstrate no significant deficits in bone mass and tend to maintain their BMD within the normal range when presenting during one to five years’ follow-up. However, this specific group requires longitudinal investigation to assess the pattern of peak bone mass achievement and the risk of future bone loss.     

Protective effect of lactofermented beetroot juice against aberrant crypt foci formation and genotoxicity of fecal water in rats

The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. N-Nitroso-N-methylurea (MNU) was used as carcinogen, which was administrated intragastrically at a dose of 50 mg/kg on the 23rd and 26th day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco 2 cell line, evaluated by MTT/NRU tests and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization and DAPI staining. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and MNU treatment, and basal diet supplemented with FBJ and MNU treatment. FBJ significantly reduced the number of ACF in MNU-treated rats (from 55 ± 18 to 21 ± 6). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 45 ± 21 to 7 ± 4. Fecal water obtained from rats fed with an MNU-containing diet induced pronounced cytotoxic and genotoxic effects in Caco 2 cells, but FBJ supplementation of the diet abolished these effects. The presence of FBJ in the diet significantly increased the count of bacteria, including Lactobacillus/Enterococcus, adhered to colonic epithelium. In conclusion, supplementation of the diet with lactofermented beetroot juice may provide protection against precancerous aberrant crypt formation and reduce the cytotoxic and genotoxic effects of fecal water.     

Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery

We have previously reported the initial clinical feasibility with our small diameter tissue engineered blood vessel (TEBV). Here we present in vitro results of the mechanical properties of the TEBVs of the first 25 patients enrolled in an arterio-venous (A-V) shunt safety trial, and compare these properties with those of risk-matched human vein and artery. TEBV average burst pressures (3490 ± 892 mmHg, n = 230) were higher than native saphenous vein (SV) (1599 ± 877 mmHg, n = 7), and not significantly different from native internal mammary artery (IMA) (3196 ± 1264 mmHg, n = 16). Suture retention strength for the TEBVs (152 ± 50 gmf) was also not significantly different than IMA (138 ± 50 gmf). Compliance for the TEBVs prior to implantation (3.4 ± 1.6%/100 mmHg) was lower than IMA (11.5 ± 3.9%/100 mmHg). By 6 months post-implant, the TEBV compliance (8.8 ± 4.2%/100 mmHg, n = 5) had increased to values comparable to IMA, and showed no evidence of dilation or aneurysm formation. With clinical time points beyond 21 months as an A–V shunt without intervention, the mechanical tests and subsequent lot release criteria reported here would seem appropriate minimum standards for clinical use of tissue engineered vessels.     

Comparison of the pedalling performance induced by magnetic and electrical stimulation cycle ergometry in able-bodied subjects

The purpose of the study was to compare the mechanical power and work generated by able-bodied subjects during functional magnetic stimulation (FMS) vs. functional electrical stimulation (FES) induced ergometer training conditions. Both stimulation methods were applied at a 30 Hz frequency to the quadriceps muscles of 22 healthy able-bodied subjects to induce cycling for 4× four minutes or until exhaustion. FMS was performed via large surface, cooled coils, while FES was applied with a typical stimulation setup used for cycling. Significantly more (p < 10⁻³) muscular power was generated by FMS (23.8 ± 9.1 W [mean ± SD]) than by FES (11.3 ± 11.3 W). Additionally, significantly more (p < 10⁻⁶) work was produced by FMS than by FES (4.413 ± 2.209 kJ vs. 0.974 ± 1.269 kJ). The increase in the work was paralleled by a significant prolongation of time to cycling failure (181.8 ± 33.4 s vs. 87.0 ± 54.0 s, respectively, p < 10⁻⁵). Compared to FES, FMS can produce more intense and longer cycling exercise in able-bodied subjects. The differing dynamic behaviour of FMS and FES in the presented measurement setup might be related to stimulation induced pain and fatigue mechanisms of the neuromuscular system.     

Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance

BackgroundGenetic variation in the perilipin (PLIN) gene may play a role in the etiology and treatment of obesity.ObjectiveTo examine different polymorphisms in the PLIN gene in relation to body-weight regulation.Methods118 subjects followed a 6 wk VLCD, followed by 1 year weight maintenance. Body-weight (BW), body-composition, leptin concentration, and polymorphisms of the PLIN gene: PLIN1:rs2289487, PLIN4:rs894160, PLIN6:rs1052700, PLIN5:rs2304795 and PLIN7:rs 2304796 were determined.ResultsBW loss during VLCD was 7.0 ± 3.1 kg (p < 0.05), and BW regain was 3.7 ± 1.4 kg (p < 0.05), including changes in body mass index (BMI), waist-circumference, body-composition and leptin concentrations (p < 0.05).Linkage disequilibria were observed between PLIN1 and PLIN4: D' > 0.9, r² = 0.72; PLIN5 and PLIN7: D' > 0.9, r² = 0.85.In men, body weight, BMI, waist circumference, body fat, leptin concentrations were significantly lower for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). In women weight loss and loss of fat mass were larger for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). For PLIN6 genotypes body weight and body fat were lower for homozygotes of the minor allele (T/T) in the men; in the women leptin concentrations were lower.The haplotype of PLIN5 and PLIN7 consisting of A/G and G/G of PLIN5 and A/A of PLIN7 showed a reduction in FM: 5.9 ± 0.6 kg vs 3.1 ± 0.4 kg, % body fat: 5.5 ± 0.6% vs 2.2 ± 0.2%, and leptin: 20.5 ± 10.8 ng/ml vs 12.9 ± 6.7 ng/ml over time in the women (p < 0.05).ConclusionSince the haplotype of the minor alleles PLIN1–4, PLIN5–7 and PLIN6, was related to body-weight regulation at a lower level of body-weight in the men as well in the women we conclude that the PLIN1–4, 6, and 5–7 locus appears as a genetic influencer of obesity risk in humans.     

Nutrition education in postmenopausal women: Changes in dietary and cardiovascular indices

ObjectiveThe aim of the current study was to examine whether a diet rich in dairy products followed by a nutrition education program for the prevention of osteoporosis could have any adverse effect on certain cardiovascular disease (CVD) risk factors over a 5-month intervention period.MethodsA total sample of 82 women (55–65 years old) was randomized to a dietary intervention group (IG: n = 42), attending biweekly nutrition education program and provided with low-fat, fortified dairy products and to a control group (CG: n = 40). Changes in dietary, biochemical and clinical indices related to CVD were determined at the end of the 5-month intervention period.ResultsThe IG was found to have a higher decrease in the percentage of energy intake derived from total fat and a higher increase in the intake of calcium, phosphorus, magnesium and potassium compared to the CG (p < 0.05). Furthermore, the IG subjects were found to have a lower increase in BMI (0.7 ± 0.1 versus 1.4 ± 0.2 Kg/m², p = 0.011) and systolic blood pressure (SBP) (2.5 ± 2.9 versus 7.8 ± 2.2 mmHg, p = 0.040) and a higher decrease in serum total cholesterol (−5.2 ± 3.3 versus 6.9 ± 5.1 mg/dl, p = 0.042) and LDL-cholesterol levels (−20.0 ± 2.6 versus −12.4 ± 4.2 mg/dl, p = 0.034) compared to the CG.ConclusionsThe findings of the current study indicate that a dietary intervention aiming to minimize the risk for osteoporosis did not have any adverse effects on CVD risk factors. On the contrary, it has induced favourable changes in BMI, serum lipids and SBP.     

Linear and non-linear analysis of heart rate variability in master athletes and healthy middle-aged non-athletes

The present study examined the autonomic cardiac modulation of veteran athletes by the use of traditional and modern methods of heart rate variability (HRV) analysis. Twenty-nine healthy male master soccer players were divided into two groups; group A consisted of fourteen participants (age 48.9 ± 5.8 years), who were engaged to regular aerobic exercise and group B of fifteen sedentary ones (age 50.8 ± 5.7 years). Sixteen age-matched non-athletes formed control group C. All participants underwent ambulatory 24-h continuous electrocardiogram monitoring for the calculation of time and frequency domain HRV indices. Additionally, Poincaré analysis SD₁ and SD₂ as well as multiresolution wavelet analysis σ_wav(16) and σ_wav(32) markers were calculated. Time-domain indices were significantly increased in group A compared to groups B and C. Group A presented greater values of SD₁ (by 43%, p < 0.01 and 34.4%, p < 0.05 than groups B and C respectively) and SD₂ (by 26% compared to B and by 34.1% to C, p < 0.05). Index σ_wav(16) was higher in group A than in B and C by 35.6% (p < 0.01) and 23.5% (p < 0.05) respectively and so did σ_wav(32) by 22% (p < 0.05) and 24% (p < 0.05). Strong correlations were reported among indices. In conclusion, physically active master athletes attain better cardiac autonomic activity than sedentary counterparts, as proved by the application of Poincaré and multiresolution wavelet analyses, which can be useful research tools of cardiac autonomic modulation in sports cardiology.     

Effects of a continuous-combined regimen of low-dose hormone therapy (oestradiol and norethindrone acetate) and tibolone on the quality of life in symptomatic postmenopausal women: A double-blind,randomised study

ObjectiveThis study compared the effects of a continuous-combined regimen of low-dose hormone therapy (LD-HT) versus tibolone and supplemental calcium/vitamin D3 (control) on quality of life (QoL) in symptomatic postmenopausal women.DesignThis study was a prospective, randomised, double-blind, comparative trial with a control group.SettingThe study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora, Brazil.PopulationA total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited. These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy.InterventionsThe patients were randomised into three groups: (1) daily treatment with 2.5 mg tibolone (n = 64), (2) 50 mg calcium carbonate + 200 IU vitamin D3 (Ca/Vit D3, n = 54) or (3) 1 mg oestradiol + 0.5 mg norethindrone acetate (E2/NETA, n = 56) for 12 weeks.Primary outcome measuresThe primary outcome was the evaluation of QoL using the Women's Health Questionnaire (WHQ) in all subjects at baseline and after 4, 8 and 12 weeks of treatment.ResultsA total of 130 women in the following groups completed the study: tibolone (n = 42), Ca/Vit D3 (n = 44) and E2/NETA (n = 44). An improved QoL based on the WHQ was observed at T0 (80.12 ± 14.04, 77.73 ± 15.3, 77.45 ± 15.4) and T12 (57.0 ± 15.5, 55.7 ± 16.7, 58.4 ± 12.6) for the tibolone, E2 + NETA and Ca/Vit D3 groups, respectively (p values <0.05). The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms. The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups (4.2 ± 26, 5.6 ± 2.8, 5.4 ± 2.8, respectively, p values <0.05). LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms (3.2 ± 1.5, 4.0 ± 1.8, 4.3 ± 2.0, respectively, p values <0.05). Adverse effects were few and mild.ConclusionsAn improved QoL was observed in the three study groups. Tibolone primarily improved sexual function, and E2/NETA exhibited a superior response for vasomotor symptoms.     

Serum paraoxonase 1 activity and oxidant/antioxidant status in Saudi women with polycystic ovary syndrome

Oxidative stress is considered to be implicated in the pathophysiology of polycystic ovary syndrome (PCOS). This study was designed to evaluate the paraoxonase 1 (PON1) activity and oxidant/antioxidant status in Saudi women with PCOS and its contribution to the risk of atherosclerosis.Lipid profile, hormonal parameters, serum PON1 activity and oxidant (malondialdehyde)/antioxidant (total antioxidant capacity (TAC) levels were analyzed in 35 patients with PCOS and 30 healthy controls using a spectrophotometric method; correlation analysis was made between these variables. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR).Women with PCOS had significantly higher fasting insulin, HOMA-IR and LH levels than controls. Lipid profiles and free androgen index (FAI) were significantly higher in women with PCOS when compared with controls. Serum PON1 activity was lower in the PCOS group (161.2 ± 6.1 U/l vs. 217.6 ± 9.3 U/l, p < 0.001) compared with controls, whereas malondialdehyde levels were higher in the PCOS group (4.26 ± 0.18 nmol/ml vs. 1.37 ± 0.12 nmol/ml, p < 0.001) compared with controls. Total antioxidant capacity was lower in the PCOS group (0.88 ± 0.10 mmol Trolox/l vs. 1.63 ± 0.17 mmol Trolox/l, p < 0.001) compared with controls. In PCOS group, serum PON1 was positively correlated with HDL-C (r = 0.425, p < 0.05) and TAC (r = 0.582, p < 0.01) but inversely correlated with HOMA-R (r = ?0.54, p < 0.01), testosterone (r = ?0.672, p < 0.01), FAI (r = ?0.546, p < 0.01) and malondialdehyde (r = ?0.610, p < 0.01).In conclusion, our data indicate that PON1 activity and antioxidant status were significantly decreased in Saudi women with PCOS. Lower serum PON1 activity might contribute to the increased susceptibility for the development of atherosclerosis risk in Saudi women with PCOS. Therefore, measurement of serum PON1 activity may be of value in assessment of women at higher risk for development of atherosclerosis risk in PCOS. However, further studies with larger sample size are needed to verify these results, and to assess the efficacy of antioxidant therapy on these patients.     

Sonographic evaluation of endothelial function in letrozole and tamoxifen users

ObjectivesStudies have shown that women previously treated for breast cancer present fewer cardiovascular events, indicating a possible protective effect of tamoxifen treatment. The effects of these aromatase inhibitors on cardiovascular protection remain controversial. The aim of this study was to compare some cardiovascular risk markers among breast cancer survivors following treatment with tamoxifen group (TMXg), letrozole group (LTZg) or no endocrine treatment group (NETg).MethodsA total of 103 breast cancer survivors: 35 using TMXg, 34 using letrozole group (LTZg) and 34 using no endocrine treatment group (NETg) were evaluated. Ultrasonographic evaluation of brachial artery flow-mediated dilation (FMD), carotid intima–media thickness (IMT) and stiffness index (β); blood total cholesterol, HDL and triglycerides were assessed.ResultsAll three groups presented similar values of HDL and IMT. TMXg showed the lowest total cholesterol (219.29 ± 36.31 mg/dL vs. 250.59 ± 38.37 mg/dL vs. 245.09 ± 35.35 mg/dL; TMXg vs. LTZg vs. NETg, respectively; p < 0.01—ANOVA), the highest triglycerides (139.34 ± 41.82 mg/dL vs. 111.35 ± 28.22 mg/dL vs. 122.09 ± 33.42 mg/dL; p < 0.01), the highest FMD (6.32 ± 2.33% vs. 4.10 ± 2.06% vs. 4.66 ± 2.52%; p < 0.01) and the lowest stiffness index (β) (5.08 ± 1.68 vs. 6.28 ± 1.75 vs. 5.99 ± 1.86; p = 0.01). LTZg did not differ significantly from NETg on any evaluated parameter.ConclusionsWe did not observe any effect of LTZg on the evaluated cardiovascular risk parameters compared to NETg. As such, the observed difference on lipid values, stiffness index (β) and FMD between women receiving tamoxifen and letrozole might be best attributed to the beneficial effect of tamoxifen than to a detrimental effect of letrozole.     

Acellular vascular grafts generated from collagen and elastin analogs

Tissue-engineered vascular grafts require long fabrication times, in part due to the requirement of cells from a variety of cell sources to produce a robust, load-bearing extracellular matrix. Herein, we propose a design strategy for the fabrication of tubular conduits comprising collagen fiber networks and elastin-like protein polymers to mimic native tissue structure and function. Dense fibrillar collagen networks exhibited an ultimate tensile strength (UTS) of 0.71 ± 0.06 MPa, strain to failure of 37.1 ± 2.2% and Young’s modulus of 2.09 ± 0.42 MPa, comparing favorably to a UTS and a Young’s modulus for native blood vessels of 1.4–11.1 MPa and 1.5 ± 0.3 MPa, respectively. Resilience, a measure of recovered energy during unloading of matrices, demonstrated that 58.9 ± 4.4% of the energy was recovered during loading–unloading cycles. Rapid fabrication of multilayer tubular conduits with maintenance of native collagen ultrastructure was achieved with internal diameters ranging between 1 and 4 mm. Compliance and burst pressures exceeded 2.7 ± 0.3%/100 mmHg and 830 ± 131 mmHg, respectively, with a significant reduction in observed platelet adherence as compared to expanded polytetrafluoroethylene (ePTFE; 6.8 ± 0.05 × 10⁵ vs. 62 ± 0.05 × 10⁵ platelets mm^–2, p < 0.01). Using a rat aortic interposition model, early in vivo responses were evaluated at 2 weeks via Doppler ultrasound and CT angiography with immunohistochemistry confirming a limited early inflammatory response (n = 8). Engineered collagen–elastin composites represent a promising strategy for fabricating synthetic tissues with defined extracellular matrix content, composition and architecture.     

Effect of vitamin C in reducing the toxicity of endosulfan in liver in rabbits

In this study, the effect of endosulfan, an organochlorine pesticide, and the ameliorating effect of vitamin C on the livers of New Zealand white rabbits were studied. Livers of the rabbits were examined grossly and histopathologically, and caspase-3 activity was detected by immunohistochemical methods. A total of twenty-four rabbits were divided into four groups (n=6). Rabbits in Group I (END) were daily given a sublethal dose of endosulfan (1 mg/kg bw) in corn oil by oral gavage for 6 weeks. Group II (END+C) received the same dose of endosulfan and additionally Vit C (20 mg/kg bw) every other day during this period. Group III (OIL+C) received corn oil daily by oral gavage and vitamin C every other day for 6 weeks. Group IV (OIL), the control group, received only corn oil daily, by oral gavage throughout the experiment. The concentration of α-endosulfan in the END group was higher in livers (0.102±0.012 ppb) than the β-endosulfan (0.072±0.001 ppb). Decreased accumulation of α and β endosulfan was observed in the END+C group (0.025±0.003 and 0.016±0.002 ppb, respectively) (p<0.0001). The most prominent gross findings at the necropsy were seen in the END group, in which swollen and pale livers were commonly observed. Hemorrhages, degenerations, necrosis, and in some rabbits bile duct hyperplasia were the marked histopathological findings of the END group. Caspase-3 positive reaction was more severe in this group than in the others. An ameliorating effect of Vit C on gross, histopathological and immunohistochemical findings was observed in the END+C group. The results revealed that endosulfan is highly toxic for rabbit livers. However, toxicity was decreased by Vit C treatment, which reduced the accumulation of endosulfan in livers four-fold.     

Teaching clinicians practical genomic medicine: 7 years’ experience in a tertiary care center

PurposeIncreased implementation of complex genetic technologies in clinical practice emphasizes the urgency of genomic literacy and proficiency for medical professionals. We evaluated our genomic education model.MethodsWe assessed the 5-day, extended format program, encompassing lectures, videos, interactive tests, practice cases, and clinical exercises. Pre- and post questionnaires assessed knowledge change, using t-tests to compare groups. Satisfaction on program completion and after 3 years were evaluated. Implementation in other centers determined acceptability.ResultsDuring 2012–2018, 774 clinicians from multiple disciplines and career stages attended 35 programs; 334 (43%) attended the 5-day extended format. Evaluations showed significant improvement of genomic literacy (mean 15.05/100 points, p < 0.001). Residents initially had higher scores than specialists (pre: 66.3 ± 17.3 vs. 58.7 ± 16.6, respectively, p = 0.002); both significantly improved, with specialists “catching up” (post: 79.1 ± 17.2 vs. 75.7 ± 15.9, nonsignificant (NS)); there was a similar trend between fellows and subspecialists (pre: 70 ± 18 vs. 59.4 ± 16.4, respectively, p = 0.007; post: 78.6 ± 16.4 vs. 73.2 ± 17.7, respectively, NS). Younger specialists (≤10 years residency) had significantly higher pre- and post scores. Absolute improvement in scores did not depend on medical specialties.ConclusionOur program is effective in improving genomics literacy for clinicians, irrespective of career length or expertise, and could be a model for improving skills in practical genomics for all medical professionals.     

Mechanical characterisation of unidirectional and cross-directional multilayered urinary bladder matrix (UBM) scaffolds

Multilayered biological scaffolds derived from mammalian extracellular matrix (ECM) have shown promising long-term clinical results when reconstructing damaged tissues and organs. Despite their established clinical applicability, experimental studies that describe the effects of alternate manufacturing protocols on an ECM's mechanical properties are lacking. In the present study the mechanical properties of multilayered ‘unidirectional’ porcine urinary bladder matrix (UBM) scaffolds were determined in favour of its longitudinal and circumferential axes. The scaffold's unidirectional mechanical properties were then compared with ‘cross-directional’ UBM scaffolds. The results showed significant variations when alternate manufacturing protocols for multilayered UBM were applied. Unidirectional longitudinal UBM remained the strongest biomaterial on a consistent basis. Its failure strength occurred at 4.79 ± 0.85 MPa compared to 3.36 ± 0.53 MPa for unidirectional circumferential and 2.91 ± 1.05 MPa for cross-directional UBM respectively (p < 0.0001). Distensibility was greatest in unidirectional circumferential UBM with failure extension occurring at 14.77 ± 1.66 mm. In comparison, failure extension occurred at 12.88 ± 0.94 mm and 13.04 ± 4.35 mm for unidirectional longitudinal and cross-directional UBM respectively (p = 0.0024). The present study demonstrates that predefined manufacturing protocols for UBM should be considered when reconstructing anatomical structures with specific mechanical requirements.