Human gender differences in fibrinolytic responses to exercise training and their determinants

Endurance exercise training improves fibrinolysis, but this training-induced adaptation may differ somewhat between men and women. We sought to determine whether the potential gender differences in training-induced changes in selected fibrinolysis measures were related to changes in adiposity and/or plasma lipoprotein lipid levels. Seventeen men and 28 women, 50-75 years old, who were generally overweight to obese, were assessed for plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) activity, t-PA antigen and plasma lipoprotein-lipid levels, and body composition before and after 6 months of endurance exercise training while on a low-fat diet. At baseline, there were no differences in fibrinolytic measures between the men and women. Baseline levels of these fibrinolytic markers in both men and women were primarily related to other fibrinolytic measures and body composition, with a smaller contribution from plasma high-density lipoprotein cholesterol (HDL-C) levels. Exercise training reduced t-PA antigen levels in both men and women, but the reduction was significantly greater in men (-1.6 +/- 0.3 versus -0.5 +/- 0.2 ng ml(-1), P = 0.007). Exercise training decreased PAI-1 activity more in men than in women (-2.6 +/- 1.4 versus +0.9 +/- 0.9 IU ml(-1), P = 0.03). Men and women both showed increased t-PA activity with exercise training to the same extent (+0.38 +/- 0.12 versus +0.36 +/- 0.24 U ml(-1)). The changes in fibrinolytic measures with exercise training in men and women were correlated with changes in other fibrinolytic measures, although in men abdominal fat changes were a strong predictor of fibrinolytic changes with training. These findings suggest that training-induced improvements in endogenous fibrinolysis markers are somewhat greater in men compared to women and may be more strongly associated with abdominal obesity in men.     

Effects of intradialytic cycling exercise on daily physical activity,physical fitness,body composition,and clinical parameters in high-volume online hemodiafiltration patients: a pilot randomized-controlled trial

Purpose

The mortality of dialysis patients treated with high-volume online hemodiafiltration (OL-HDF) is better than hemodialysis, but is still higher than healthy population. Low daily physical activity increases cardiovascular mortality. Addition of intradialytic exercise (IDX) program might improve physical activity and health status in OL-HDF patients. This pilot open-labeled randomized-controlled trial was conducted to evaluate the effects of IDX on physical activity and other clinical parameters in OL-HDF patients.

Methods

Twelve OL-HDF patients were randomized into control (n?=?6) or IDX (n?=?6) groups. The subjects in IDX group were trained to exercise using a cycle ergometer for 60 min during each OL-HDF session. Physical activity measured as daily step count using a wrist-worn triaxial accelerometer, physical fitness, or cardiorespiratory fitness assessed by VO₂max and other physical performance tests, lean body mass determined by the Dual-energy X-ray absorptiometry (DXA), quality of life (QOL), and various parameters were compared between baseline and 6 months.

Results

The baseline physical activity status was comparable. Following 6-month IDX, the physical activity was significantly improved in IDX group [+?1048.79 (+?741.50,?+?2792.54) vs. ? 362.06 (? 1626.82, ? 167.47) steps/day, p?=?0.01], while physical fitness and QOL were unchanged. The lean body mass parameters were preserved in the IDX group while seemed to decrease in the control group. Serum albumin was significantly increased in the IDX group (p?=?0.01). The hemoglobin changes were significantly better (p?=?0.01) and the erythropoietin resistance index was significantly lower in the IDX group (p?=?0.03). Phosphate reduction was significantly greater in the IDX group (p?=?0.04).

Conclusions

IDX could improve physical activity and other metabolic parameters in OL-HDF patients and these might contribute to further improvement in clinical and survival outcomes.

Trial registration

ClinicalTrials.gov Registration: NCT03353844.

     

Mechanisms of CNS myelin inhibition: evidence for distinct and neuronal cell type specific receptor systems

Following injury to the adult mammalian central nervous system, regenerative growth of severed axons is very limited. The lack of neuronal repair is often associated with significant functional deficits, and depending on the severity of injury, may result in permanent paralysis distal to the site of injury. A detailed understanding of the molecular mechanisms that limit neuronal growth in the injured spinal cord is an important step toward the development of specific strategies aimed at restoring functional connectivity lost as a consequence of injury. While rapid progress is being made in defining the molecular identity of CNS growth inhibitory constituents, comparatively little is known about their receptors and downstream signaling mechanisms. Emerging new evidence suggests that the mechanisms for myelin inhibition are likely to be complex, involving multiple and distinct receptor systems that may operate in a redundant manner. Furthermore, the relative contribution of a specific ligand-receptor system to bring about growth inhibition may greatly vary among different neuronal cell types. Myelin-associated glycoprotein (MAG), for example, employs different mechanisms to inhibit neurite outgrowth of cerebellar, sensory, and retinal ganglion neurons in vitro. Nogo-A harbors distinct growth inhibitory regions, which employ different signaling mechanisms. The Nogo-66 receptor 1 (NgR1), a shared ligand binding component in a receptor complex for Nogo-66, MAG, and OMgp, participates in neuronal growth cone collapse to acutely presented myelin inhibitors, but is dispensable for longitudinal neurite outgrowth inhibition on substrate-bound Nogo-66, MAG, OMgp, or crude CNS myelin in vitro. Consistent with the idea of cell-type specific mechanisms for myelin inhibition, different types of CNS neurons possess very different regenerative capacities and respond differently to experimental treatment strategies in vivo. We speculate that differences in regenerative axonal growth among different fiber systems are a reflection of their intrinsic ability to elongate axons and their distinct cell surface receptor profiles to respond to the growth inhibitory extracellular milieu. The existence of cell type specific mechanisms to impair regenerative axonal growth in the CNS may have important implications for the development of treatment strategies. Depending on the fiber tract injured, different ligand-receptor systems may need to be targeted in order to elicit robust and long-distance regenerative axonal growth.     

Automated implant segmentation in cone-beam CT using edge detection and particle counting

Purpose

To develop a fully automated, accurate and robust segmentation technique for dental implants on cone-beam CT (CBCT) images.

Methods

A head-size cylindrical polymethyl methacrylate phantom was used, containing titanium rods of 5.15 mm diameter. The phantom was scanned on 17 CBCT devices, using a total of 39 exposure protocols. Images were manually thresholded to verify the applicability of adaptive thresholding and to determine a minimum threshold value \(({T}_{\mathrm{min}})\) . A three-step automatic segmentation technique was developed. Firstly, images were pre-thresholded using \({T}_{\mathrm{min}}\) . Next, edge enhancement was performed by filtering the image with a Sobel operator. The filtered image was thresholded using an iteratively determined fixed threshold \(({T}_{\mathrm{edge}})\) and converted to binary. Finally, a particle counting method was used to delineate the rods. The segmented area of the titanium rods was compared to the actual area, which was corrected for phantom tilting.

Results

Manual thresholding resulted in large variation in threshold values between CBCTs. After applying the edge-enhancing filter, a stable \({T}_{\mathrm{edge}}\) value of 7.5 % was found. Particle counting successfully detected the rods for all but one device. Deviations between the segmented and real area ranged between \(-\) 2.7 and + \(14.4\,\hbox {mm}^{2}\) with an average absolute error of \(2.8\,\hbox {mm}^{2}\) . Considering the diameter of the segmented area, submillimeter accuracy was seen for all but two data sets.

Conclusion

A segmentation technique was defined which can be applied to CBCT data for an accurate and fully automatic delineation of titanium rods. The technique was validated in vitro and will be further tested and refined on patient data.     

Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration

Citrate which chelates ionized calcium can be used as regional anticoagulation in continuous venovenous hemofiltration (CVVH). This is the first study conducted to examine the potentially additive benefit effect of regional citrate anticoagulation (RCA) on polymorphonuclear (PMN) cell degranulation of myeloperoxidase (MPO) and cytokines production in patients with critically acute kidney injury (AKI) undergoing CVVH treatment. This prospective randomized controlled trial was conducted in 20 critically ill patients with AKI who underwent CVVH. The patients were randomized into regional citrate group (n=10) and heparin group (n=10). The pre-dilution CVVH with polyethersulfone dialyzers were utilized in both groups. The levels of pre-filter and post-filter MPO as well as inflammatory and anti-inflammatory cytokines were measured at baseline, 6h, and 24 h after initiating CVVH. In the heparin group, the post-filter serum MPO levels were significantly higher than the pre-filter (median 49.0 vs. 60.5 ng/mL, P<0.05) at 6 h. There were no significant differences between pre- and post-dialyzer MPO levels in the citrate group. Citrate could significantly decrease systemic pre-filter serum MPO levels from baseline at 6 h (median 43.5 vs. 17.3 ng/mL, P<0.01) as well as IL-8 levels (P<0.05) whereas heparin provided only significant TNF-α reduction (P<0.05). The CVVH circuit survival in the citrate group was longer than the heparin group. In conclusion, citrate, utilized as a regional anticoagulant in CVVH, can reduce both membrane bioincompatibility-induced and systemic oxidative stress and inflammation, and can prolong CVVH circuit survival time.     

Halogenated benzoate derivatives of altholactone with improved anti-fungal activity

Altholactone exhibited the anti-fungal activity with a high MIC value of 128 μg ml^?1 against Cryptococcus neoformans and Saccharomyces cerevisiae. Fifteen ester derivatives of altholactone 1–15 were modified by esterification and their structures were confirmed by spectroscopic methods. Most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-Bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentration (MIC) values against C. neoformans at 16 μg ml^?1_, while the 4-bromo-, 4-iodo-, and 1-bromo-3-chlorobenzoates (11–13) displayed potent activity against S. cerevisiae with MIC values of 1 μg ml^?1. In conclusion, this analysis indicates that the anti-fungal activity of altholactone is enhanced by addition of halogenated benzoyl group to the 3-OH group.     

Chromosome Abnormalities and Absolute Telomere Lengths of Leukocytes from Silk Weavers with Emphasis on Potential Genotoxicity and Mutagenicity of Silk Dyes

Objectives: This study is aimed to assess the possible genotoxicity and mutagenicity of silk dyes on silk weavers.Methods: Peripheral blood leukocytes were obtained from 24 silk weavers and 24 age- and sex-matched controls innortheastern Thailand. After mitogen stimulation in culture, chromosome abnormalities were examined using Giemsabanding and the absolute telomere length (aTL) was measured with SYBR green qRT-PCR. To confirm genotoxic andmutagenic effects of silk dyes, leukocytes from one each of healthy male and female volunteers were cultured withvarious concentrations of 3 dark red silk dyes under the presence of mitogen. Chromosome abnormalities and thetelomere length were determined as above. Results: The proportion of normal metaphase in the silk weaving workerswas significantly lower than that in controls. The frequency of chromosome aberrations was higher in the silk weaversthan in control group. Polyploidy was detected only in the silk weavers. The aTL was significantly shorter in the silkweavers than in control group (p < 0.05). When leukocytes from normal volunteers were stimulated with mitogen underthe presence of various concentrations of 3 silk dyes, suppressed the mitotic index (MI) and normal metaphase, whereasthe proportion of prophase and the incomplete chromosome forming increased significantly. All dyes induced polyploidy.Dye #CA5 induced structural changes in male leukocytes, whereas #30 induced the changes in female leukocytes.The #CA5 increased aTL of normal leukocytes in a dose-dependent manner. Conclusions: All dyes, especially #CA5,have high genotoxicity and mutagenicity to induce chromosome aberrations and telomeric instability. Taken all thoseresults together, regular health checking of silk weavers who have been exposed to those dyes is critically necessaryto prevent various chemical-induced carcinogenesis.     

Comparison of conventional and TACT (Tuned Aperture Computed Tomography) digital subtraction radiography in detection of pericrestal bone-gain

Tuned Aperture Computed Tomography or TACT is a relatively new technique that transforms correlated two-dimensional images into a three-dimensional display. Associating TACT with digital subtraction radiography (TACT-DSR) may enhance its use in the detection of diseases. This study aims to assess observer performance in the task of detecting simulated bone-gain in periodontal defects, comparing conventional and TACT DSR. Buccal, lingual and proximal pericrestal bony defects in a human dry skull were imaged with and without increments of crushed-bone and wax mixtures using standardized vertical bitewing projections, acquired with an intraoral digital receptor in a tomographic X-ray machine. One hundred and twenty pairs of baseline and follow-up images were obtained for each imaging modality. Post-acquisition processing including image-registration, density-correction and subtraction operation were applied to both transmission images and TACT-slices. Eight calibrated observers evaluated the presence or absence of pericrestal bone-gain using a 5-point confidence scale. Details about the location of periodontal defects and the amount of bone-gain for each subtracted image were recorded and used in the statistical analysis. Observer performance and study design factors were analyzed by means of receiver operating characteristic (ROC) curve analysis and ANOVA. Mean values of areas under ROC curves for bone-gain detection performance were 0.82 for conventional DSR and 0.90 for TACT-DSR. TACT-DSR provided statistically superior detection performance of simulated periodontal bone-gain over conventional DSR for tooth-obscured defects (p = 0.001) and for the smallest bone mass (p = 0.024). The findings support TACT-DSR's potential to provide greater sensitivity and technique flexibility in detecting periodontal bone-gain than standard DSR.     

N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis

AIM To evaluate attenuating properties of N-acetylcysteine (NAC) on oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis (NASH).METHODS Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 8) was free accessed to regular dry rat chow (RC) for 6 wk.Group 2 (NASH, n = 8) was fed with 100% fat diet for 6 wk. Group 3 (NASH NAC20, n = 9) was fed with 100% fat diet plus 20 mg/kg per day of NAC orally for 6 wk. All rats were sacrificed to collect blood and liver samples at the end of the study.RESULTS The levels of total glutathione (GSH)and hepatic malondialdehyde (MDA) were increased significantly in the NASH group as compared with the control group (GSH; 2066.7 ± 93.2 vs 1337.5 ± 31.5 μmol/L and MDA; 209.9± 43.9 vs 3.8 ±1.7 μmol/g protein, respectively, P ＜ 0.05). Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation.NAC treatment improved the level of GSH (1394.8 ± 81.2 μmol/L, P ＜ 0.05), it did not affect MDA (150.1 ± 27.0 μmol/g protein), but led to a decrease in fat deposition and necroinflammation.CONCLUSION NAC treatment could attenuate oxidative stress and improve liver histology in rats with NASH.