Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis.

Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed

Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers.

In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDA <sub>EBC</sub> generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter

Laparoscopic herniorrhaphy in children with acute inflammatory diseases of the abdominal cavity

Institutul de Cercetări științifice în Chirurgia Pediatrică, Universitatea Națională de Cercetări Medicale „N.Pirogov”, Moscova, Rusia, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Prezența unui proces inflamator-distructiv acut în cavitatea abdominală este pe larg considerată ca o contraindicație pentru herniorafia laparoscopică simultană. Material și metode: În perioada 2010-2012, 240 de copii cu vîrsta 5-14 ani, au fost spitalizați cu manifestările clinice ale abdomenului acut și au fost supuși intervențiilor chirurgicale urgente. În timpul laparoscopiei la 29 pacienți (18 băieți și 11 fete) a fost depistat processus vaginalis persistent (PVP): în 25 de cazuri unilateral și în 4 cazuri - bilateral. Nouăsprezece copii din acest lot au fost diagnosticați cu formele distructive ale apendicitei acute (în 6 cazuri complicate cu peritonită locală), 5 – cu pelvioperitonită, 4 – cu limfadenită mezenterică acută și 1 copil – cu apoplexie ovariană. La toți pacienții au fost efectuate intervenții simultane – asanarea focarului inflamator și ligaturarea subcutanată endo-asistată (SEAL) a PVP. Rezultate: Nu a fost înregistrat nici un caz de conversie. După intervenția de asanare a focarului inflamator (apendicectomie, rezecție de ovar, etc.) a fost efectuată SEAL conform metodei modificate de autori. Durata SEAL nu a depășit 6 minute pentru hernia unilaterală și 9 minute în cazuri bilaterale. Postoperator toți copii au primit un tratament standard. În toate cazurile evoluția postoperatorie a fost favorabilă. Complicații abdominale sau la nivelul canalului inghinal nu au fost înregistrate. Examenul ultrasonor și testele de laborator au confirmat rezolvarea completă a procesului inflamator. Toți pacienții au fost externați complet recuperați. Concluzii: Herniorafia laparoscopică simultană la copiii cu procese acute inflamatorii în cavitatea abdominală nu este urmată de elevarea riscului complicațiilor postoperatorii.Introduction: The presence of an acute inflammatory and destructive process in the abdominal cavity is commonly a contraindication to the one-stage laparoscopic herniorrhaphy. Material and methods: From 2010 to 2012, 240 children, 5-14 years of age, were admitted to hospital with a clinical picture of acute abdomen and all of them were urgently operated on. During laparoscopy in 29 patients (18 boys and 11 girls) a persisted processus vaginalis (PPV) was found: unilateral in 25 cases and bilateral in 4 cases. In 19 children from this group destructive forms of acute appendicitis (in 6 cases complicated by local peritonitis) were diagnosed as well as 5 – pelvioperitonitis, 4 – acute mesenteric lymphadenitis, and 1 – ovarian apoplexy. All patients underwent simultaneous procedures – both inflammatory focus treatment and subcutaneous endo-assisted ligation (SEAL) of PPV. Results: There was no conversion in any case. After the intervention for treatment of inflammatory focus (appendectomy, ovarian resection, etc.) the SEAL was performed according to our modification. SEAL duration was not more than 6 minutes for unilateral hernia and 9 minutes for bilateral. Postoperatively, all children received a standard therapy. In all cases the postoperative period was favorable. Complications in abdominal cavity or inguinal canals were not registered. Ultrasound examination and blood tests confirmed a complete relief of the inflammatory process. All patients were discharged with full recovery. Conclusions: Simultaneous laparoscopic herniorrhaphy in children with acute inflammation in the abdominal cavity does not increase the risk of postoperative complications

Repeated surgery for reccurent varicocele in children

The frequency of varicocele recurrences after surgery is an extremely variable quantity (0,5-35%). Most studies show that microsurgical inguinal or subinguinal ligation of veins provides significantly fewer relapses (0,5-3,7%). During the period 2009 - 2016, we treated 14 patients 12,5-17 years age with recurrent varicocele. At 4 ones previously produced retroperitoneal ligation of testicular veins by open access, 9 - laparoscopic ligation. In 13 cases, laparoscopic ligation of residual testicular vein was performed. In 1 patient relapse was occurred after an open ligation of testicular vein. Based on angiography results with measurement of venous pressure in the left renal vein we had decided to hold subinguinal microsurgical ligation veins. 4 months after that operation varicocele grade 3 relapsed again. We performed laparoscopic revision and clipping of the residual veins and simultaneous microsurgical ligation of expanded venous plexus in the scrotum by skrototomy through the Vesling`s line. Follow-up of 14-42 months demonstrate an absence of recurrence. In 2 patients in the development of a hydrocele occurred in the earl postoperative period, which disappeared after 4.5 and 8 months spontaneously. Another patient after repeated laparoscopic procedure suggests decrease of volume of the left testis by 35% relative to the right. Conclusion. According our experience we can recommend laparoscopic ligation of residual testicular veins as good choice in children with relapse of varicocele

Malondialdehyde and anion patterns in exhaled breath condensate among subway workers.

Underground transportation systems can contribute to the daily particulates and metal exposures for both commuter and subway workers. The redox and metabolic changes in workers exposed to such metal-rich particles have yet to be characterized. We hypothesize that the distribution of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) are modified depending on exposures. Particulate number and size as well as mass concentration and airborne metal content were measured in three groups of nine subway workers (station agents, locomotive operators and security guards). In parallel, pre- and post-shift EBC was collected daily during two consecutive working weeks. In this biological matrix, malondialdehyde, lactate, acetate, propionate, butyrate, formate, pyruvate, the sum of nitrite and nitrate (ΣNO <sub>x</sub> ) and the ratio nitrite/nitrate as well as metals and nanoparticle concentrations was determined. Weekly evolution of the log-transformed selected biomarkers as well as their association with exposure variables was investigated using linear mixed effects models with the participant ID as random effect. The professional activity had a strong influence on the pattern of anions and malondialdehyde in EBC. The daily number concentration and the lung deposited surface area of ultrafine particles was consistently and mainly associated with nitrogen oxides variations during the work-shift, with an inhibitory effect on the ΣNO <sub>x</sub> . We observed that the particulate matter (PM) mass was associated with a decreasing level of acetate, lactate and ΣNO <sub>x</sub> during the work-shift, suggestive of a build-up of these anions during the previous night in response to exposures from the previous day. Lactate was moderately and positively associated with some metals and with the sub-micrometer particle concentration in EBC. These results are exploratory but suggest that exposure to subway PM could affect concentrations of nitrogen oxides as well as acetate and lactate in EBC of subway workers. The effect is modulated by the particle size and can correspond to the body's cellular responses under oxidative stress to maintain the redox and/or metabolic homeostasis

Urinary Malondialdehyde (MDA) Concentrations in the General Population-A Systematic Literature Review and Meta-Analysis.

Oxidative stress has been associated with various inflammation-related human diseases. It is defined as an imbalance between the production and elimination of reactive oxygen species (ROS). ROS can oxidize proteins, lipids, and DNA, and some of these oxidized products are excreted in urine, such as malondialdehyde (MDA), which is considered a biomarker for oxidative damage of lipids. To interpret changes of this biomarker as a measure of oxidative species overproduction in humans, a background range for urinary MDA concentration in the general population is needed. We sought to establish urinary MDA concentration ranges for healthy adult populations based on reported values in the available scientific literature. We conducted a systematic review and meta-analysis using the standardized protocol registered in PROSPERO (CRD42020146623). EMBASE, PubMed, Web of Science, and Cochrane library databases were searched from journal inception up to October 2020. We included 35 studies (divided into 47 subgroups for the quantitative analysis). Only studies that measured creatinine-corrected urinary MDA with high-performance liquid chromatography (HPLC) with mass spectrometry (MS), fluorescence detection, or UV photometry were included. The geometric mean (GM) of urinary MDA concentration was 0.10 mg/g creatinine and 95% percentile confidence interval (CI) 0.07-0.12. Age, geographical location but not sex, and smoking status had a significant effect on urinary MDA concentrations. There was a significant increasing trend of urinary MDA concentrations with age. These urinary MDA values should be considered preliminary, as they are based on mostly moderate to some low-quality evidence studies. Although urinary MDA can reliably reflect excessive oxidative stress in a population, the influence of physiological parameters that affect its meaning needs to be addressed as well as harmonizing the chemical analytical methods

Producers of Engineered Nanomaterials-What Motivates Company and Worker Participation in Biomonitoring Programs?

Production and handling of engineered nanomaterials (ENMs) can yield worker exposure to these materials with the potential for unforeseen negative health effects. Biomonitoring enables regular exposure and health assessment and an effective risk management. We aimed to identify factors influencing biomonitoring acceptance according to hierarchical positions of ENM producers. Managers and workers were invited to complete an online questionnaire. Forty-three companies producing or handling ENMs such as titanium dioxide (61%) and multi-walled carbon nanotubes (44%) participated. The majority of managers (72%) and all workers responded positively to participating in biomonitoring studies. The main reasons for refusing participation included concerns about data confidentiality and sufficient knowledge about ENM health and safety. Acquisitions of individual study results, improvement of workers' safety, and help to the development of ENM-specific health and safety practice were among the most valuable reasons for positively considering participation. All workers indicated feeling comfortable with biomonitoring procedures of exhaled air sampling-about half were similarly comfortable with exhaled breath condensate, urine, and buccal cell sampling. The majority of both workers and managers stated that participation in a biomonitoring program should take place during working hours. Although our survey only had limited participation, our results are useful in designing appropriate biomonitoring programs for workers exposed to ENMs

Associating Air Pollution with Cytokinesis-Block Micronucleus Assay Parameters in Lymphocytes of the General Population in Zagreb (Croatia).

Air pollution is recognized as one of the most serious public health issues worldwide and was declared to be a leading environmental cause of cancer deaths. At the same time, the cytokinesis-block micronucleus (CBMN) assay serves as a cancer predictive method that is extensively used in human biomonitoring for populations exposed to environmental contamination. The objective of this cross-sectional study is two-fold: to evaluate genomic instability in a sample (N = 130) of healthy, general population residents from Zagreb (Croatia), chronically exposed to different levels of air pollution, and to relate them to air pollution levels in the period from 2011 to 2015. Measured frequencies of CBMN assay parameters were in agreement with the baseline data for the general population of Croatia. Air pollution exposure was based on four factors obtained from a factor analysis of all exposure data obtained for the examined period. Based on the statistical results, we did not observe a significant positive association between any of the CBMN assay parameters tested and measured air pollution parameters for designated time windows, except for benzo(a)pyrene (B[a]P) that showed significant negative association. Our results show that measured air pollution parameters are largely below the regulatory limits, except for B[a]P, and as such, they do not affect CBMN assay parameters' frequency. Nevertheless, as air pollution is identified as a major health threat, it is necessary to conduct prospective studies investigating the effect of air pollution on genome integrity and human health

Air Pollution and Primary DNA Damage among Zagreb (Croatia) Residents: A Cross-Sectional Study.

More than eight million premature deaths annually can be attributed to air pollution, with 99% of the world's population residing in areas below recommended air quality standards. Hence, the present study aimed to examine the association between primary DNA damage and air pollution data among 123 participants enrolled between 2011 and 2015 in Zagreb, Croatia. While most measured air pollutants adhered to regulatory limits, benzo[a]pyrene concentrations bound to PM <sub>10</sub> exceeded them. Factorial analysis narrowed down air pollution data to four exposure factors (particulate matter, two metal factors, and other pollutants). Despite the absence of significant positive associations between modeled air pollution exposure factors and comet assay descriptors (tail length, tail intensity, tail moment, and highly damaged nuclei), the critical health implications of air pollution warrant further investigations, particularly with biomarkers of exposure and different biomarkers of effect in populations facing air pollution exposure

РОССИЙСКО-БРИТАНСКИЙ СЕМИНАР МОЛОДЫХ УЧЕНЫХ «БИОЛОГИЧЕСКАЯ ОБРАТНАЯ СВЯЗЬ В КОРРЕКЦИИ ДИСФУНКЦИИ ТАЗОВОГО ДНА У ДЕТЕЙ». Москва, 24–25 октября 2017 г.

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