Effect of L-ascorbic add supplementation on testicular oxidative stress and endocrine disorders in mature male rats exposed to intensive swimming exercise

In order to investigate the ameliorative potential of L-ascorbic acid on intensive swimming exercise induced testicular oxidative stress, 18 Wistar male rats (age: 3 months, weight: 127.5 ± 5.3 g) were randomly divided into the following groups: (i) control group (CG,n = 6); (ii) experimental group (EG,n = 6); and (iii) supplemented group (SG,n = 6). An exercise protocol of 3 h swimming per day, five days per week was followed for 6 weeks in EG and SG with no exercise in CG. In SG, L-ascorbic acid was supplied orally at a dose of 25-mg/kg of bodyweight each day for 6 weeks. A significant decrease (P < 0.05) was noted in paired testicular weights, epididymal sperm count, testicular Δ⁵, 3β-hydroxyseroid dehydrogenase, 17β-hydroxyseroid dehydrogenase, plasma levels of testosterone luteinizing hormone, follicle stimulating hormone, prolactin, the numbers of preleptotine spermatocytes, midpachytene spermatocytes and stage 7 spermatids of stage VII seminiferous epithelium cycle in EG when compared with CG. A significant elevation (P < 0.05) in plasma corticosterone and testicular content of malondialdehyde along with a significant reduction (P < 0.05) in glutathione, ascorbic acid, α-tocopherol, superoxide dismutase, catalase and glutathione-peroxidase, and glutathione-S-transferase were noted in testes of EG compared with CG. No significant change was noted in final bodyweight or numbers of spermatogonia-A among the groups. Furthermore, L-ascorbic acid supplementation restored the above parameters to the control level. Conclusion  It can be concluded that intensive swimming exercise induced oxidative stress causes dysfunctions in the male reproductive system, which can be protected by L-ascorbic acid.     

Therapy for minimal residual tumor disease: β‐Galactosylceramide inhibits the growth of recurrent HPV16‐associated neoplasms after surgery and chemotherapy

Natural killer T (NKT) cells are potent modulators of antitumor immunity. Their protective effects can be achieved upon their activation by glycolipid ligands presented in the context of the CD1d molecule. These CD1d‐binding glycolipid antigens have been described as potent therapeutic agents against tumors, infections, as well as autoimmune diseases. Immunoregulatory and therapeutic effects of glycolipid ligands depend on their structure and modes of administration. Therefore, more studies are needed for optimization of the particular therapeutic settings. This study was focused on the tumor‐inhibitory effects of 12 carbon acyl chain β‐galactosyl ceramide (C12 β‐D ‐Galactosyl Ceramide; β‐GalCer(C12)) on the growth of human papillomavirus type 16 (HPV16)‐associated neoplasms transplanted in syngeneic mice. Treatment of tumor‐bearing mice with β‐GalCer(C12) 3–14 days after tumor cell transplantation significantly inhibited the growth of the major histocompatability complex (MHC) Class I‐positive (TC‐1), as well as MHC Class I‐deficient (TC‐1/A9) HPV16‐asssociated tumors. Moreover, administration of β‐GalCer(C12) after surgical removal of TC‐1 tumors inhibited the growth of tumor recurrences. Similar results were obtained in the treatment of tumors after chemotherapy. β‐GalCer(C12) treatment turned out to be also synergistic with immunotherapy based on administration of IL‐12‐producing cellular vaccines. These results suggest that β‐GalCer(C12), whose antitumor effects have so far not been studied in detail, can be effective for the treatment of minimal residual tumor disease as well as an adjuvant for cancer immunotherapy.     

Multi-Objective Optimization of Process Parameters during Micro-Milling of Nickel-Based Alloy Inconel 718 Using Taguchi-Grey Relation Integrated Approach

This research investigates the machinability of Inconel 718 under conventional machining speeds using three different tool coatings in comparison with uncoated tool during milling operation. Cutting speed, feed rate and depth of cut were selected as variable machining parameters to analyze output responses including surface roughness, burr formation and tool wear. It was found that uncoated and AlTiN coated tools resulted in lower tool wear than nACo and TiSiN coated tools. On the other hand, TiSiN coated tools resulted in highest surface roughness and burr formation. Among the three machining parameters, feed was identified as the most influential parameter affecting burr formation. Grey relational analysis identified the most optimal experimental run with a speed of 14 m/min, feed of 1 μm/tooth, and depth of cut of 70 μm using an AlTiN coated tool. ANOVA of the regression model identified the tool coating parameter as most effective, with a contribution ratio of 41.64%, whereas cutting speed and depth of cut were found to have contribution ratios of 18.82% and 8.10%, respectively. Experimental run at response surface optimized conditions resulted in reduced surface roughness and tool wear by 18% and 20%, respectively.     

Bovine Polyomavirus-1 (Epsilonpolyomavirus bovis): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans

Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the “cytopathic-inflammatory pathology pattern” proposed in the pathogenesis of Human polyomavirus-1-associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin–Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed.     

Mixed Infection of Blackcurrant with a Novel Cytorhabdovirus and Black Currant-Associated Nucleorhabdovirus

A virome screen was performed on a new breeding line, KB1, of blackcurrant. Rhabdovirus-like particles were observed by electron microscopy in ultrathin sections of flower stalks, and the complete genome sequence of a novel virus, provisionally named blackcurrant rhabdovirus 2 (BCRV2), was determined and verified using high-throughput sequencing. The genomic organization of BCRV2 was characteristic of cytorhabdoviruses (family Rhabdoviridae) and included seven genes: 3′-N-P′-P-P3-M-G-L-5′. BLASTP analysis revealed that the putative L protein had the highest amino acid sequence identity (75%) with strawberry virus 2. BCRV2 was detected in Cryptomyzus galeopsidis, but efficient transmission by this aphid was not confirmed. Of note, we observed coinfection of the KB1 line with blackcurrant-associated rhabdovirus (BCaRV) by RT-PCR. This is likely the first evidence of the presence of a cyto- and a nucleorhabdovirus in a single host.     

Neurophysiological Markers for Monitoring Exercise and Recovery Cycles in Endurance Sports

The current study analyzes the suitability and reliability of selected neurophysiological and vegetative nervous system markers as biomarkers for exercise and recovery in endurance sport. Sixty-two healthy men and women, endurance trained and moderately trained, performed two identical acute endurance tests (running trial 1 and running trial 2) followed by a washout period of four weeks. Exercise protocol consisted of an acute running trial lasting 60 minutes. An intensity corresponding to 95% of the heart rate at individual anaerobic threshold for 40 minutes was followed by 20 minutes at 110%. At pre-exercise, post-exercise, three hours post-exercise and 24 hours post-exercise, experimental diagnostics on Brain-derived neurotrophic factor (BDNF), heart rate variability (HRV), Stroop Color and Word Test (SCWT), and Short-Form McGill Pain Questionnaire (SF-MPQ) were performed. Significant changes over time were found for all parameters (p < .05). Furthermore, there was an approached statistical significance in the interaction between gender and training status in BDNF regulation (F₍₃₎ = 2.43; p = 0.06), while gender differences were found only for LF/HF-ratio (3hPoEx, F₍₃₎ = 3.40; p = 0.002). Regarding the reliability, poor ICC-values (< 0.5) were found for BDNF, Stroop sensitivity and pNN50, while all other parameters showed moderate ICC-values (0.5-0.75). Plasma-BDNF, SCWT performance, pain perception and all HRV parameters are suitable exercise-sensitive markers after an acute endurance exercise. Moreover, pain perception, SCWT reaction time and all HRV parameters show a moderate reliability, others rather poor. In summary, a selected neurophysiological and vegetative marker panel can be used to determine exercise load and recovery in endurance sports, but its repeatability is limited due to its vaguely reliability. Key points

• Pain perception and the Stroop test have moderate reliability in the use of exercise and recovery markers after two identical exercise loads in endurance sports
• Markers of heart rate variability also show moderate reliability as biomarkers after intense endurance exercise under identical conditions.
• There are associations between neurophysiological markers and inflammatory blood markers after endurance exercise that are partially associated with gender and training status

Key words: NNervous system, monitoring training, biomarkers, reliability, executive function, heart rate variability     

Treatment with Paracetamol Can Interfere with the Intradialytic Optical Estimation in Spent Dialysate of Uric Acid but Not of Indoxyl Sulfate

Optical online methods are used to monitor the haemodialysis treatment efficiency of end stage kidney disease (ESKD) patients. The aim of this study was to analyse the effect of the administration of UV-absorbing drugs, such as paracetamol (Par), on the accuracy of optical monitoring the removal of uremic toxins uric acid (UA) and indoxyl sulfate (IS) during standard haemodialysis (HD) and haemodiafiltration (HDF) treatments. Nine patients received Par in daily dosages 1–4 g for 30 sessions. For 137 sessions, in 36 patients the total daily dosage of UV-absorbing drugs was less than 500 mg, and for 6 sessions 3 patients received additional UV-absorbing drugs. Par administration slightly affected the accuracy of optically assessed removal of UA expressed as bias between optically and laboratory-assessed reduction ratios (RR) during HD but not HDF employing UV absorbance of spent dialysate (p < 0.05) at 295 nm wavelength with the strongest correlation between the concentration of UA and absorbance. Corresponding removal of IS based on fluorescence at Ex280/Em400 nm during HD and HDF was not affected. Administration of UV-absorbing drugs may in some settings influence the accuracy of optical assessments in spent dialysate of the removal of uremic solutes during haemodialysis treatment of ESKD patients.