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Background: Photodynamic antimicrobial chemotherapy (PACT) is a promising modality for eradication of microorganisms from the wound. This study aimed to investigate the effectiveness of PACT using indocyanine green (ICG) for reduction of bacterial load of oral ulcers in rats and its impact on the healing process., Methods: In this experimental study, 50 adult male Sprague Dawley rats were recruited. Oral ulcers were surgically made on the left cheek mucosa, and animals were randomly assigned into five groups (n = 10). Wound site in groups 1, 2, and 3 was irrigated with the sterile saline (0.9%), chlorhexidine (CHX; 0.2%), and ICG solutions (1 mg/mL), respectively. Group 4 was exposed to laser irradiation using 810 nm diode laser on continuous-wave mode for 30 seconds (fluence: 55 J/cm 2 , power: 300 mW, spot size: 4.5 mm). In group 5, PACT was performed using topical application of ICG followed by laser irradiation in the same way as the previous group. Bacterial load of oral ulcers was assessed before and after each treatment modality. Besides, rats were sacrificed on the 5th day post ulceration and histological features of healing were evaluated., Results: Bacterial load was significantly reduced merely in the PACT-ICG-treated group by one log (P < .0001). Animals in the PACT-ICG-treated group also showed an accelerated healing in comparison with others on the 5th day of an experiment., Conclusion: Photodynamic antimicrobial chemotherapy using topical application of ICG has a potential to reduce the bacterial load of oral ulcers and accelerate wound repair. Therefore, it can be considered as an alternative to currently available modalities for wound management., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Intrathoracic fat volume, more specifically, epicardial fat volume, is an emerging imaging biomarker of adverse cardiovascular events. The purpose of this work is to show the feasibility and reproducibility of intrathoracic fat volume measurement applied to contrast-enhanced multidetector computed tomography images. A retrospective cohort study of 62 subjects free of cardiovascular disease (55% females, age = 49 ± 11 years) conducted from 2008 to 2011 formed the study group. Intrathoracic fat volume was defined as all fat voxels measuring -50 to -250 Hounsfield Unit within the intrathoracic cavity from the level of the pulmonary artery bifurcation to the heart apex. The intrathoracic fat was separated into epicardial and extrapericardial fat by tracing the pericardium. The measurements were obtained by 2 readers and compared for interrater reproducibility. The fat volume measurements for the study group were 141 ± 72 cm 3 for intrathoracic fat, 58 ± 27 cm 3 for epicardial fat, and 84 ± 50 cm 3 for extrapericardial fat. There was no statistically significant difference in intrathoracic fat volume measurements between the 2 readers, with correlation coefficients of 0.88 ( P = .55) for intrathoracic fat volume and -0.12 ( P = .33) for epicardial fat volume. Voxel-based measurement of intrathoracic fat, including the separation into epicardial and extrapericardial fat, is feasible and highly reproducible from multidetector computed tomography scans., Competing Interests: Conflict of Interest: None reported.

Exposure to diesel exhaust particles (DEP) via the gastrointestinal route may impose risk of cancer in the colon and liver. We investigated the effects of DEP given in the diet to Big Blue rats by quantifying a panel of markers of DNA damage and repair, mutation, oxidative damage to proteins and lipids, and antioxidative defence mechanisms in colon mucosa cells, liver tissue and the blood compartment. Seven groups of rats were fed a diet with 0, 0.2, 0.8, 2, 8, 20 or 80 mg DEP/kg feed for 21 days. DEP induced a significant increase in DNA strand breaks in colon and liver. There was no effect on oxidative DNA damage (8-oxodG) in colon or liver DNA or in the urine. However, the mRNA expression of OGG1, encoding an enzyme involved in repair of 8-oxodG, was increased by DEP in both liver and colon. DNA adduct levels measured by 32P-post-labelling were elevated in colon and liver, and the expression of ERCC1 gene was affected in liver, but not in colon. In addition to these effects, DEP exposure induced apoptosis in liver. There was no significant change in mutation frequency in colon or liver. The levels of oxidative protein modifications (oxidized arginine and proline residues) were increased in liver accompanied by enhanced vitamin C levels. In plasma, we found no significant effects on oxidative damage to proteins and lipids, antioxidant enzymes or vitamin C levels. Our data indicate that gastrointestinal exposure to DEP induces DNA adducts and oxidative stress resulting in DNA strand breaks, enhanced repair capacity of oxidative base damage, apoptosis and protein oxidation in colon mucosa cells and liver.

The potential beneficial or adverse affect of prolonged dietary administration of moderate to high doses (1-100 mg/kg diet) of the antioxidants, lycopene, quercetin and resveratrol or a mixture of lycopene and quercetin was investigated in male F344 rats. Selected markers for toxicity and defense mechanisms were assayed in blood, liver and colon and the impact of the antioxidant administrations on putative preneoplastic changes in liver and colon was assessed. The dietary carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (200 mg/kg diet) served as a pro-oxidant, genotoxicity and general toxicity control. IQ increased the levels of protein and DNA oxidation products in plasma, the area of glutathione S-transferase-placental form positive (GST-P) foci in the liver as well as the number of colonic aberrant crypt foci (ACF). All antioxidants and the antioxidant combination significantly increased the level of lymphocytic DNA damage, to an extent comparable with the effect induced by IQ. In contrast to the control group where no GST-P foci were detected, GST-P foci were detected in animals exposed to quercetin, lycopene and the combination of the two. However, the increase in the volume of GST-P foci did not reach statistical significance. The present results indicate that moderate to high doses of common dietary antioxidants can damage lymphocyte DNA and induce low levels of preneoplastic liver lesions in experimental animals. Long-term exposure to moderate to high doses of antioxidants may thus via pro-oxidative mechanisms and non-oxidative mechanisms modulate carcinogenesis.

Artichoke (Cynara scolymus L.), an edible vegetable from the Mediterranean area, is a good source of natural antioxidants such as vitamin C, hydroxycinnamic acids, and flavones. The antioxidant activity of aqueous-organic extracts of artichoke were determined using three methods: (a) free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) scavenging, (b) ferric-reducing antioxidant power (FRAP), and (c) inhibition of copper(II)-catalyzed in vitro human low-density lipoprotein (LDL) oxidation. In addition, the present study was performed to investigate the ability of the edible portion of artichoke to alter in vivo antioxidative defense in male rats using selected biomarkers of antioxidant status. One gram (dry matter) had a DPPH(*) activity and a FRAP value in vitro equivalent to those of 29.2 and 62.6 mg of vitamin C and to those of 77.9 and 159 mg of vitamin E, respectively. Artichoke extracts showed good efficiency in the inhibition in vitro of LDL oxidation. Neither ferric-reducing ability nor 2,2'-azinobis(3-ethylbenzothiazolin-6-sulfonate) radical scavenging activity was modified in the plasma of the artichoke group with respect to the control group. Among different antioxidant enzymes measured (superoxide dismutase, gluthatione peroxidase, gluthatione reductase, and catalase) in erythrocytes, only gluthatione peroxidase activity was elevated in the artichoke group compared to the control group. 2-Aminoadipic semialdehyde, a protein oxidation biomarker, was decreased in plasma proteins and hemoglobin in the artichoke-fed group versus the control group. In conclusion, the in vitro protective activity of artichoke was confirmed in a rat model.

The health effects of diesel exhaust particles (DEP) are thought to involve oxidative damage. We have investigated the effect of intratracheal DEP instillation to guinea pigs in three groups of 12 animals each given 0, 0.7, or 2.1 mg. Five days later guinea pigs exposed to DEP had increased levels of oxidized amino acids (gamma-glutamyl semialdehyde), DNA strand breaks, and 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in the lung. Bulky DNA ad- ducts were not significantly elevated in the lung. The antioxidant enzyme activity of glutathione reductase was increased in the lung of DEP-exposed guinea pigs, whereas glutathione peroxidase and superoxide dismutase enzyme activities were unaltered. There was no difference in DNA strand breaks in lymphocytes or urinary excretion of 8-oxodG at the two doses tested. Protein oxidations in plasma and in erythrocytes were not altered by DEP exposure. The concentrations of ascorbate in liver, lung, and plasma were unaltered by the DEP exposure. The results indicate that in guinea pigs DEP causes oxidative DNA damage rather than bulky DNA adducts in the lung. Guinea pigs, which are similar to humans with respect to vitamin C metabolism, may serve as a new model for the study of oxidative damage induced by particulate matter.

Ambient particulate air pollution assessed as outdoor concentrations of particulate matter less than or equal to 2.5 micro m in diameter (PM(2.5)) in urban background has been associated with cardiovascular diseases at the population level. However, the significance of individual exposure and the involved mechanisms remain uncertain. We measured personal PM(2.5) and carbon black exposure in 50 students four times in 1 year and analyzed blood samples for markers of protein and lipid oxidation, for red blood cell (RBC) and platelet counts, and for concentrations of hemoglobin and fibrinogen. We analyzed protein oxidation in terms of gamma-glutamyl semialdehyde in hemoglobin (HBGGS) and 2-aminoadipic semialdehyde in hemoglobin (HBAAS) and plasma proteins (PLAAS), and lipid peroxidation was measured as malondialdehyde (MDA) in plasma. Median exposures were 16.1 micro g/m(3) for personal PM(2.5) exposure, 9.2 micro g/m(3) for background PM(2.5) concentration, and 8.1 X 10(-6)/m for personal carbon black exposure. Personal carbon black exposure and PLAAS concentration were positively associated (p < 0.01), whereas an association between personal PM(2.5) exposure and PLAAS was only of borderline significance (p = 0.061). A 3.7% increase in MDA concentrations per 10 micro g/m(3) increase in personal PM(2.5) exposure was found for women (p < 0.05), whereas there was no significant relationship for the men. Similarly, positive associations between personal PM(2.5)exposure and both RBC and hemoglobin concentrations were found only in women (p < 0.01). There were no significant relationships between background PM(2.5) concentration and any of the biomarkers. This suggests that exposure to particles in moderate concentrations can induce oxidative stress and increase RBCs in peripheral blood. Personal exposure appears more closely related to these biomarkers potentially related to cardiovascular disease than is ambient PM(2.5) background concentrations.

Administration of apple juice, black currant juice, or a 1:1 combination of the two juices significantly decreased the level of the lipid peroxidation biomarker malondialdehyde in plasma of female rats, whereas the protein oxidation biomarker 2-amino-adipic semialdehyde, was significantly increased following administration of orange juice, black currant juice, or the 1:1 combination of apple and black currant juice. A significant increase in 2-amino-adipic semialdehyde was also observed in control rats given sucrose, fructose, and glucose in the drinking water at concentrations approximating the average carbohydrate levels in the employed fruit juices. None of the fruit juices were found to affect the activities of antioxidant enzymes in red blood cells or hepatic glutathione S-transferase. Hepatic quinone reductase activity, on the other hand, was significantly increased by grapefruit juice, apple juice, and black currant juice. The total daily intake of a selected subset of flavonoid aglycones ranged from 0.2 to 4.3 mg, and quercetin was found to be a minor constituent of all the juices investigated. In a parallel study, rats were fed quercetin at doses ranging from 0.001 to 10 g/kg of diet. However, no effects were observed on hepatic glutathione S-transferase or quinone reductase activities, plasma redox status, or the activity of red blood cell antioxidant enzymes. Overall, the results of the present study suggest that commonly consumed fruit juices can alter lipid and protein oxidation biomarkers in the blood as well as hepatic quinone reductase activity, and that quercetin may not be the major active principle. The observation that natural carbohydrates are capable of mediating oxidative stress in vivo warrants further studies due to the central role refined and unrefined carbohydrates play in human nutrition.

The contribution of oxidative stress, different types of DNA damage and expression of DNA repair enzymes in colon and liver mutagenesis induced by 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) was investigated in four groups of six Big Blue rats fed diets with 0, 20, 70, and 200 mg IQ/kg for 3 weeks. There were dose-response relationships of DNA adducts ((32)P-postlabeling) and DNA strand breaks (comet assay) in colon and liver tissues, with the highest levels of DNA adducts and strand breaks in the colon. There was dose-dependent induction of mutations in both the colon and the liver, and the same IQ dose produced two-fold more cII mutations in the liver compared with the colon. The IQ-induced mutation spectrum in the colon was not significantly different to that of control rats. The expression of ERCC1 and OGG1 was higher in the colon than liver, and was unaffected by the IQ diet. Investigations of oxidative stress biomarkers produced inconclusive results. Oxidative DNA damage detected by the endonuclease III enzyme and 7-hydro-8-oxo-2'-deoxyguanosine in colon, liver and/or urine was unaltered by IQ. However, there was increased level of gamma-glutamyl semialdehyde in liver proteins, indicating a higher rate of protein oxidation in the liver following IQ administration. In plasma and erythrocytes there were unaltered levels of oxidized protein, malondialdehyde, and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase) indicating no systemic oxidative stress. However, the level of total vitamin C was increased in plasma, with the largest fraction being in the reduced form. In conclusion, our results indicate that DNA adducts rather than oxidative stress are responsible for the initiation of IQ-induced carcinogenesis of the liver and colon. A lower frequency of mutations in the colon than in the liver could be related to higher expression of DNA repair enzymes in the former.

A sucrose-rich diet has repeatedly been observed to have cocarcinogenic actions in the colon and liver of rats and to increase the number of aberrant crypt foci in rat colon. To investigate whether sucrose-rich diets might directly increase the genotoxic response in the rat colon or liver, we have added sucrose to the diet of Big Blue rats, a strain of Fischer rats carrying 40 copies of the lambda-phage on chromosome 4. Dietary sucrose was provided to the rats for 3 weeks at four dose levels including the background level in the purified diet [3.4% (control), 6.9%, 13.8%, or 34.5%] without affecting the overall energy and carbohydrate intake. We observed a dose-dependent increase in the mutation frequency at the cII site in the colonic mucosa with increased sucrose levels, reaching a 129% increase at the highest dose level. This would indicate a direct or indirect genotoxic effect of a sucrose-rich diet. No significant increase in mutations was observed in the liver. To seek an explanation for this finding, a variety of parameters were examined representing different mechanisms, including increased oxidative stress, changes in oxidative defense, effects on DNA repair, or changes in the background levels of DNA adducts. Sucrose did not increase the number of DNA strand breaks or oxidized bases assessed as endonuclease III-sensitive sites or 8-oxodeoxyguanosine in colon or liver. DNA repair capacity as determined by expression of the rERCC1 or rOGG1 genes was not increased in colon or liver, but the background level of DNA adducts (I-compounds) as determined by (32)P postlabeling was significantly decreased in colon. This decrease in colon I-compounds correlated inversely with both mutation frequency and ERCC1 DNA repair gene expression. Dietary sucrose did not change liver apoptosis or cell turnover as determined by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling assay and proliferating cell nuclear antigen. An increase in liver ascorbate was also observed, whereas oxidative damage was not observed in proteins or lipids in liver cytosol or in blood plasma. We conclude that a sucrose-rich diet directly or indirectly increases the mutation frequency in rat colon in a dose-dependent manner and concomitantly decreases the level of background DNA adducts, without a direct effect on the expression of major DNA repair enzyme systems. We also conclude that an oxidative mechanism for this effect of sucrose is unlikely. This is the first demonstration of a genotoxic action of increased dietary sucrose in vivo. Both sucrose intake and colon cancer rates are high in the Western world, and our present results call for an examination of a possible direct relationship between the two.

This intervention study was designed as cross-over (four women, one man) with three doses of black currant/apple (1:1) juice (750, 1000, and 1500 mL) for one week corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin per day. Urinary excretion of quercetin increased significantly with dose and with time. The fraction excreted in urine was constant 0.29-0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate increased during intervention due to ascorbate from the juice. Total plasma malondialdehyde decreased with time during 1500 mL juice intervention. Plasma protein 2-adipic semialdehyde residues, increased with time and dose, and glutathione peroxidase increased with juice dose, whereas other selected markers of oxidative status did not change. These effects might be related to several components of the juice and cannot be attributed solely to its quercetin content.

A new optical resonator based on the combination of a generalized self-filtering unstable resonator (GSFUR) and a positive-branch unstable resonator (PBUR) in a three-mirror scheme is reported. It is shown both theoretically and experimentally that a nearly diffraction-limited Gaussian-output laser beam with a large mode volume can be obtained with this cavity design. The laser cavity is particularly interesting for use in high-threshold pumped gain media and eliminates some disadvantages of the SFUR and GSFUR designs. This resonator, with an effective magnification of -6.16, was applied to a pulsed Nd:YAG laser in free-running and in Q-switched modes of operation. The output energy was approximately 70 mJ, 5.5 times greater than when a single GSFUR design was used. The output beam had a pulse duration of approximately 30 ns in the Q-switched mode of operation and a beam divergence of 0.26 mrad. The required relations for the GSFUR-PBUR optical design and the output energy were derived and verified experimentally.