The systemic antiangiogenic effect of intravitreal aflibercept injection in a mouse model of retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness and intravitreal anti-vascular endothelial growth factor (VEGF) injection is becoming a first-line choice for treatment of ROP. However, there is a major concern that intravitreally injected anti-VEGF agents could escape from the eye into the systemic circulation and impair systemic development. Moreover, escaped anti-VEGF agents could have an effect on the retina of the fellow eye. In this study, we investigated the hematogenous effect of a single intravitreal anti-VEGF injection in a mouse model of ROP. Here, we showed that single intravitreal aflibercept injection to one eye can affect body weight gain, the fellow eye, and renal vessels, although no apparent effect was observed in brain vessels. Furthermore, this hematogenous effect was dose-dependent. Our results provide very important insights into the clinical use of anti-VEGF agents for ROP treatment.

Comparison of Bio-C Pulpo and MTA Repair HP with White MTA: effect on liver parameters and evaluation of biocompatibility and bioactivity in rats.

AIM: To evaluate the tissue response promoted by Bio-C Pulpo (Bio), MTA Repair HP (MTA-HP) and White MTA (WMTA) and whether these materials cause liver changes in a rat experimental model. METHODOLOGY: Polyethylene tubes filled with Bio, MTA-HP and WMTA, and empty tubes (control group, CG) were implanted into the subcutaneous tissues of rats for 7, 15, 30 and 60 days. Inflammatory reaction score (IRS), capsule thickness, number of inflammatory cells (IC), von Kossa reaction, interleukin-6 (IL-6) and alkaline phosphatase (ALP) immunohistochemistry reactions were performed. Combined methods, von Kossa followed by immunohistochemistry for detection of ALP, were performed. At 60 days, the serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels were measured and liver fragments were collected for histological analysis; the data were assessed by one-way ANOVA analysis followed by Sidak's post-test. The biocompatibility and bioactivity data were subjected to the two-way ANOVA analysis followed by Tukey post hoc test, except the IRS. The IRS data were subjected to the Kruskal-Wallis ANOVA non-parametric test followed by Dunn's test (p ≤ .05). RESULTS: No significant difference was detected in serum GOT and GPT concentrations and in the number of hepatocytes among the experimental and CG samples. Although Bio-C Pulpo had the highest IC and IL-6-immunolabelled cells (p < 0.0001) at all periods, no significant difference was observed in the IRS among the materials, except at 60 days. In this period, the WMTA had lower IRS. All groups had a significant reduction in the capsule thickness and in the number of IC and IL-6-immunolabelled cells over time. Bio-C Pulpo, MTA-HP and WMTA specimens had greater immunoexpression of ALP than CG (p < .0001). At all periods, von Kossa-positive and birefringent structures were observed in the capsules around the materials. ALP-immunolabelled cells were also seen near von Kossa-positive structures. CONCLUSIONS: Bio-C Pulpo, MTA-HP and WMTA materials did not cause morphological changes in the liver and no significant alteration in the serum GOT and GPT levels. Moreover, these bioceramic materials were biocompatible and exhibited bioactive potential. However, Bio-C Pulpo induced greater inflammatory infiltrate than MTA-HP and WMTA at all periods.

Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma.

This study aimed to identify the proteomic changes produced by curcumin treatment following stimulation of the host immune system in a rat model of malignant mesothelioma. We analyzed the proteomes of secondary lymphoid organs from four normal rats, four untreated tumor-bearing rats, and four tumor-bearing rats receiving repeated intraperitoneal administrations of curcumin. Cross-comparing proteome analyses of histological sections of the spleen from the three groups first identified a list of eighty-three biomarkers of interest, thirteen of which corresponded to proteins already reported in the literature and involved in the anticancer therapeutic effects of curcumin. In a second step, comparing these data with proteomic analyses of histological sections of mesenteric lymph nodes revealed eight common biomarkers showing a similar pattern of changes in both lymphoid organs. Additional findings included a partial reduction of the increase in spleen-circulating biomarkers, a decrease in C-reactive protein and complement C3 in the spleen and lymph nodes, and an increase in lymph node purine nucleoside phosphorylase previously associated with liver immunodeficiency. Our results suggest some protein abundance changes could be related to the systemic, distant non-target antitumor effects produced by this phytochemical.

Analysis of the Pharmacokinetics of Suppository Forms of Bacteriophages.

Pharmacokinetics of suppository forms of bacteriophages was studied on male Chinchilla rabbits. Suppositories with various composition of bacteriophages were administered once per rectum to rabbits, and the presence of phage particles was estimated in the blood, urine, and feces over 24 h. Pharmacokinetic study showed that the phages were detected in the blood, urine, and feces at various terms of the experiment irrespective of the size of viral particles, which confirmed the possibility of their systemic effects after rectal administration. Thus, the use of suppository form of bacteriophages can ensure the presence of phage particles even in infection foci that cannot directly contact with the preparation.

Local and systemic effects of low-level light therapy with light-emitting diodes to improve erythema after fractional ablative skin resurfacing: a controlled study.

Therapy with light-emitting diodes (LED) has been associated with the reduction of erythema and accelerated wound healing. LED phototherapy has been used in various clinical practices including post-laser wound healing enhancement. Fractional laser resurfacing is one of the popular dermatological procedures; however, the duration and degree of downtime may limit daily life activity and studies on the effect of LED low-level light therapy (LED-LLLT) on post-ablative laser wound care are still limited. To evaluate local and systemic effects of LED-LLLT on post-ablative laser erythema and wound healing acceleration after fractional ablative laser resurfacing. The study was divided into two arms. First, a prospective split-face randomized controlled and single-blinded study involved 17 patients (split-face group) to determine the local and systemic effect of LED-LLLT. Patients with acne scars or rhytides were treated with a single session of fractional CO2 laser followed by 830/590 nm LED-LLLT on one side of their faces. The duration of post-laser erythema, the erythema index, and transepidermal water loss were collected at baseline, and compared with 7-daily follow-up visits posttreatment for the non LED- and LED-treated sides. The second controlled arm of the study was performed on an additional 19 subjects (CO2 group). The patients received a single fractional CO2 laser treatment without any LED-LLLT with the same follow-up protocol. All measurements were compared with the results from the patients from the split-face group. In the split-face group, the duration of erythema post laser was equal (7.4 ± 2.8 days). No significant reduction in the erythema index and transepidermal water loss was seen in the LED-treated vs the non-treated side (p values = 0.99 and 0.78 respectively). For the second part of the study that compared the results between the split-face group and the control CO2 only group, the duration of the post-laser erythema was comparable (p value = 0.32). However, the percentage difference of the erythema index from baseline in the split-face group was significantly lower than the CO2 group on days 1, 4, 5, and 7 post-laser treatment (p value = 0.03 on days 1, 4, 5, and 0.04 on day 7) and the LED-treated side provided the lowest percentage difference of the erythema index followed by the non LED-treated side compared with the control CO2 only group. 830/590 nm LED-LLLT may provide both local and systemic effects on the degree of post-ablative laser erythema in human skin, however, appropriate protocol settings should be considered to achieve a significant clinical outcome.

Lead-interacting proteins and their implication in lead poisoning.

Lead is an important heavy metal used worldwide in several applications, especially in industry. People exposed to lead can develop a wide range of symptoms associated with lead poisoning. Many effects of lead poisoning are reported in the literature, showing a compromising of whole body health, with symptoms related to cardiovascular, immune, bone, reproductive, hematological, renal, gastrointestinal, and nervous system. However, the molecular lead targets as well as the pathways affected by lead poisoning are not completely described. The aim of this study was to construct a map of metabolic pathways impaired in lead poisoning by evaluating which biomolecules are directly affected by lead. Through manual literature curation, we identified proteins which physically interact with lead and subsequently determined the metabolic pathways those proteins are involved with. At total, we identified 23 proteins involved with heme synthesis, calcium metabolism, neurotransmission, among other biological systems, which helps to understand the wide range of lead-poisoning symptoms.

Synthesis, characterization and efficacy of silver nanoparticles against Aedes albopictus larvae and pupae.

Silver nanoparticles have been studied in a wide range of medical and entomological research works due to their eco-friendly aspects. In our study salicylic acid (SA) and its derivative, 3,5-dinitrosalicylic acid (DNS), were used in a one-step synthesis of silver nanoparticles (AgNPs). First, UV-vis absorption spectroscopy was used to detect the formation of AgNPs. Second, the synthesized nanoparticles were characterized using scanning electron microscope, transmission electron microscope; energy-dispersive spectroscopy, X-ray diffraction analysis and Fourier transform infrared spectroscopy. I, II, III and IV Instar larvae and pupae of Ae. Albopictus were exposed to various concentrations of SA, DNS and synthesized AgNPs for 24h to evaluate the larvicidal and pupicidal effect. In larvicidal bioassay of SA, moderate mortality was observed at 180ppm against Ae. Albopictus with LC50 values of 86, 108, 135 and 141ppm for instar larvae I, II, III and IV, respectively. Synthesized AgNPs showed highest mortality rate at 12ppm and the LC50 values of SAAgNPs were 1.2ppm (I), 1.4ppm (II), 1.8ppm (III), 2.0ppm (IV) and 1.4ppm (pupae). Whereas LC50 values of DNSAgNPs were 1.2ppm (I), 1.5ppm (II), 1.8ppm (III) 2.3ppm (IV) and 1.4ppm (pupae). Moreover, the investigations toward the systemic effect of the tested substances on the fourth instar larvae of Ae. albopictus was evaluated and the levels of total proteins, esterases, acetylcholine esterase, and phosphatase enzymes were found to be significantly decreased as compared with the control. These results highlight that SA-AgNPs and DNS-AgNPs are potential tools to control larval populations of mosquito.

Systemic effects of acute cigarette smoke exposure in mice.

CONTEXT: Cigarette smoke (CS) causes both pulmonary and extrapulmonary disorders. OBJECTIVE: To determine the pulmonary and extrapulmonary effects of acute CS exposure in regard to inflammation, oxidative stress and DNA damage. MATERIALS AND METHODS: Mice were exposed to CS for 10 days and then their lungs, heart, liver, pancreas, kidneys, gastrocnemius muscle and subcutaneous (inguinal and flank) and visceral (retroperitoneum and periuterus) adipose tissues were excised. Bronchoalveolar lavage fluid samples were obtained for differential cell analysis. Inflammatory cell infiltration of the tissues was assessed by immunohistochemistry for Mac-3(+) cells, F4/80(+) cells and CD45(+) cells. Oxidative stress was determined by immunohistochemistry for thymidine glycol (a marker of DNA peroxidation) and 4-hydroxy hexenal (a marker of lipid peroxidation), by enzyme-linked immunosorbent assay for protein carbonyls (a marker of protein peroxidation) and by measurements of enzyme activities of glutathione peroxidase, superoxide dismutase and catalase. DNA double-strand breaks were assessed by immunohistochemistry for γH2AX. RESULTS: CS exposure-induced inflammatory cell infiltration, oxidative stress and DNA damage in the lung. Neither inflammatory cell infiltration nor DNA damage was observed in any extrapulmonary organs. However, oxidative stress was increased in the heart and inguinal adipose tissue. DISCUSSIONS: Induction of inflammatory cell infiltration and DNA damage by acute CS exposure was confined to the lung. However, an increased oxidative burden occurred in the heart and some adipose tissue, as well as in the lung. CONCLUSIONS: Although extrapulmonary effects of CS are relatively modest compared with the pulmonary effects, some extrapulmonary organs are vulnerable to CS-induced oxidative stress.

Behavioral Effects of the Mixture and the Single Compounds Carbendazim, Fipronil, and Sulfentrazone on Zebrafish (Danio rerio) Larvae.

Pesticides are often detected in freshwater, but their impact on the aquatic environment is commonly studied based on single compounds, underestimating the potential additive effects of these mixtures. Even at low concentrations, pesticides can negatively affect organisms, altering important behaviors that can have repercussions at the population level. This study used a multi-behavioral approach to evaluate the effects of zebrafish larvae exposure to carbendazim (C), fipronil (F), and sulfentrazone (S), individually and mixed. Five behavioral tests, thigmotaxis, touch sensitivity, optomotor response, bouncing ball test, and larval exploratory behavior, were performed to assess potential effects on anxiety, fear, and spatial and social interaction. Significant changes were observed in the performance of larvae exposed to all compounds and their mixtures. Among the single pesticides, exposure to S produced the most behavioral alterations, followed by F and C, respectively. A synergistic effect between the compounds was observed in the C + F group, which showed more behavioral effects than the groups exposed to pesticides individually. The use of behavioral tests to evaluate pesticide mixtures is important to standardize methods and associate behavioral changes with ecologically relevant events, thus creating a more realistic scenario for investigating the potential environmental impacts of these compounds.

Muscle contraction time after caffeine intake is faster after 30 minutes than after 60 minutes.

BACKGROUND: This study aimed to determine the optimal time point, either 30 or 60 minutes, at which muscle reactivity to caffeine administration is highest. Unlike previous studies that focused on the nervous system response, we employed tensiomyography (TMG) to directly assess the effects of caffeine on muscle fibers. METHODS: TMG measurements were performed on the gastrocnemius medialis muscle of 42 male athletes who regularly consumed caffeine. Participants received a dose of 6 mg/kg body weight and TMG measurements were taken prior to caffeine intake, as well as 30 and 60 minutes afterward. RESULTS: Analysis of TMG parameters including time to contraction (Tc), time delay (Td), and maximal displacement (Dm) revealed that muscles exhibited faster contractions and greater stiffness at the 30-minute mark compared to both pre-caffeine intake and the 60-minute time point. Time exerted a significant main effect on Tc (F(2, 246) = 12.09, p < .001, ή2p = 0.09), Td (F(2, 246) = 3.39, p = .035, ή2p = 0.03), and Dm (F(2, 246) = 6.83, p = .001, ή2p = 0.05), while no significant effect of body side was observed. CONCLUSIONS: The findings indicate that muscle contraction time (Tc) and delay time (Td) are influenced by the time elapsed since caffeine ingestion, with the fastest responses occurring after 30 minutes. Additionally, a systemic effect of caffeine was observed, as there were no discernible differences in measurements between the two sides of the body. TMG proves to be an effective noninvasive method for assessing muscle responses following caffeine administration.

Systemic effect of calcium silicate-based cements with different radiopacifiers-histopathological analysis in rats.

Aim: This in vivo study aimed to examine the systemic effects of contemporary calcium silicate cements (CSC) contain different radiopacifiers in rats. Materials & Methods: Polyethylene tubes filled with BIOfactor MTA (BIO), Neo MTA Plus (NEO), MTA Repair HP (REP), Biodentine (DENT) and empty tubes (control group) were implanted into the subcutaneous tissues of 80 male Spraque Dawley rats for 7 and 30 days (n = 8). After 7 and 30 day, samples of liver and kidney tissues were submitted to histopathological analysis. Blood samples were collected to evaluate changes in hepatic and renal functions of rats. Wilcoxon and post hoc Dunn Bonferroni tests were used to compare between the 7th and 30th days in order to evaluate the histopathological data. Paired-sample t-test was used to compare laboratory values between the 7th and 30th days, ANOVA analysis and a post hoc Tukey test were used to compare values between groups (p < 0.05). Results: On the 7th day, REP, BIO and NEO groups were statistically similar in kidney tissue and the degree of inflammation was found to be significantly higher in these groups compared to the control and DENT groups. On the 30th day, the degree of inflammation of the REP and NEO groups in the kidney tissue was found to be significantly higher than the control, BIO and DENT groups. Although the inflammation in the liver was moderate and mild on the 7th and 30th days, no statistically significant difference was observed between the groups. Vascular congestion was evaluated as mild and moderate in kidney and liver in all groups, and no statistically significant difference was observed between the groups. While there was no statistically significant difference between the groups in the 7th day AST, ALT and urea values, when the creatinine values were compared, the DENT and NEO groups were found to be statistically similar and significantly lower than the control group. On the 30th day, ALT values were statistically similar between the groups. The AST values of the BIO group were found to be significantly higher than the DENT group. While BIO, DENT, NEO and control groups had statistically similar urea values, the REP group was found to be significantly higher than the other groups. The creatinine value of the REP group was significantly higher than the groups other than the control group (p < 0.05). Conclusion: CSCs with different radiopacifiers had similar and acceptable effects on the histological examination of the kidneys and liver systemically, and serum ALT, AST, urea, creatinine levels.

How Periodontitis or Periodontal Bacteria Can Influence Alzheimer's Disease Features? A Systematic Review of Pre-Clinical Studies.

BACKGROUND: The negative effects of periodontitis on systemic diseases, including diabetes, cardiovascular diseases, and Alzheimer's disease (AD), have been widely described. OBJECTIVE: This systematic review aimed to gather the current understanding of the pathophysiological mechanisms linking periodontitis to AD. METHODS: An electronic systematic search of the PubMed/MEDLINE, Scopus, and Embase databases was performed using the following PECO question: How can periodontitis or periodontal bacteria influence Alzheimer's disease features?". Only preclinical studies exploring the biological links between periodontitis and AD pathology were included. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), and the Syrcle and Camarades protocols were used to assess the risk of bias. RESULTS: After a systematic screening of titles and abstracts (n = 3,307), thirty-six titles were selected for abstract reading, of which 13 were excluded (k = 1), resulting in the inclusion of 23 articles. Oral or systemic exposure to periodontopathogens or their byproducts is responsible for both in situ brain manifestations and systemic effects. Significant elevated rates of cytokines and amyloid peptides (Aß) and derivate products were found in both serum and brain. Additionally, in infected animals, hyperphosphorylation of tau protein, hippocampal microgliosis, and neuronal death were observed. Exposure to periodontal infection negatively impairs cognitive behavior, leading to memory decline. CONCLUSIONS: Systemic inflammation and brain metastatic infections induced by periodontal pathogens contribute to neuroinflammation, amyloidosis, and tau phosphorylation, leading to brain damage and subsequent cognitive impairment.

Substances of abuse and their effect on SAR-CoV-2 pathogenesis.

Following the emergence of SARS-CoV-2, various reports suggest that there has been a significant increase in substance abuse due to social distancing and related issues. Several reports have suggested the impact of chronic substance use on individuals' physiological and psychological health. Therefore, there is a need to know the impact of SARS-CoV-2 on persons with substance use disorders. Individuals with substance use disorders are the most vulnerable groups and are at a high risk of SARS-CoV-2 infection due to their already existing health issues associated with substance use. This review discusses some of the molecular and systemic/organic effects chronic substance use such as alcohol, nicotine, marijuana (cannabis), opioids, methamphetamine, and cocaine have on SARS-CoV-2 infectivity and its potential cause for worsened disease outcomes in persons with substance use disorder. This will provide healthcare providers, public health policies, and researchers with the needed knowledge to address some of the many challenges faced during the Covid-19 pandemic to facilitate treatment strategies for persons with substance use disorders.

New Approaches to Manage Asian Soybean Rust (Phakopsora pachyrhizi) Using Trichoderma spp. or Their Antifungal Secondary Metabolites.

Attempts have been made to determine the in vitro and in planta suppressive potential of particular Trichoderma strains (T16 and T23) and their secondary metabolites (SMs) against Asian soybean rust (ASR) incited by Phakopsora pachyrhizi. Aside from the previously identified SMs 6-pentyl-α-pyrone (6PAP) and viridiofungin A (VFA), the chemical structures of harzianic acid (HA), iso-harzianic acid (iso-HA), and harzianolide (HZL) were characterized in this study. Our results indicate that exposure of urediospores to 200 ppm 6PAP completely inhibits germination. A slightly higher dosage (250 ppm) of HZL and VFA reduces germination by 53.7% and 44%, respectively. Germ tube elongation seems more sensitive to 6PAP than urediospore germination. On detached leaves, application of conidia of T16 and T23 results in 81.4% and 74.3% protection, respectively. Likewise, 200 ppm 6PAP recorded the highest ASR suppression (98%), followed by HZL (78%) and HA (69%). Treatment of undetached leaves with 6PAP, HA, or HZL reduces ASR severity by 84.2%, 65.8%, and 50.4%, respectively. Disease reduction on the next, untreated trifoliate by T23 (53%), T16 (41%), HZL (42%), and 6PAP (32%) suggests a translocation or systemic activity of the SMs and their producers. To our knowledge, this study provides the first proof for controlling ASR using antifungal SMs of Trichoderma. Our findings strongly recommend the integration of these innovative metabolites, particularly 6PAP and/or their producers in ASR management strategies.

Tannic acid is a gastroprotective that regulates inflammation and oxidative stress.

This study investigated the gastroprotective effect of TA against gastric ulcer in mice, and its possible mechanisms of action. The effects were investigated in a model of ethanol and ethanol/HCl induced ulcers, and physical barrier test. Quantification of oxidative stress mediators and inflammatory cytokines in gastric tissue was performed. The involvement of sulfhydryl compounds (-SH), nitric oxide (NO), prostaglandin E2 (PGE2), potassium channels (K +ATP) and opioid receptors in gastroprotection were investigated. Oral treatment with TA at a dose of 50 mg/kg resulted in 97.96% and 94.20% (reduction in gastric injury) of gastroprotection, against injuries caused by ethanol and ethanol/HCL, respectively, in addition to having a systematic effect. TA promotes increased levels of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), as well as reduced levels of malondialdehyde (MDA) reaction to thiobarbituric acid and myeloperoxidase (MPO). In addition, there was reduction in levels of tumor necrosis factor alpha (TNF-α) and interleukins (IL) IL-1ß and IL-6 and increased IL-10. The gastroprotective activity of TA involved K +ATP channels and the production of -SH, NO and PGE2, demonstrating multiple mechanisms of action. The results of the present study suggest that TA may be a gastroprotective agent counteracting oxidative and inflammatory stress.

Effect of Radiotherapy and Low-Level Laser Therapy on Circulating Blood Cells of Rats.

Introduction: This study aimed to investigate the effect of low-level laser therapy (LLLT) on the blood cell count when applied to parotid glands of rats irradiated by volumetric modular arc therapy (VMAT). Methods: Thirty-two adult male Wistar rats were used in this study. Samples were randomly assigned to three groups: control group (CG, n = 8), immediate laser group (24 hours) (ILG, n=12), and late laser group (120 hours) (LLG, n=12). The two laser groups were previously subjected to VMAT radiotherapy in a single dose of 12 Gy. LLLT with an AsGaAl laser (660 nm, 100 mW) was applied at three points in the region of the parotid glands, right side, with the energy of 2 J per point (20s, 70 J/cm2) and a spot size of 0.0028 cm2 for 10 consecutive days. In the euthanasia, blood samples were obtained by cardiac puncture. The samples from each group were processed by an automatic method and analyzed for erythrogram, leukogram and platelet count values. The data were analyzed by ANOVA and each LLLT time point was analyzed in relation to the control group, with a significance level less than 0.05. Results: Groups using LLLT had higher red blood cell counts, being higher in the LLG (P = 0.000). The hematimetric indices MCV (P = 0.002) and MCH (P = 0.009) were lower than the control group, especially when compared to the group using LLLT 120h after radiotherapy (LLG). White blood cell counts were lower in the groups with radiotherapy and immediate use of LLLT (ILG) (P = 0.011), mainly at the expense of lymphocytes (P = 0.002). Conclusion: The results suggest a potential systemic effect of LLLT, especially on circulating red blood cell counts, regardless of their time of immediate or late use of radiotherapy.

Tracing the toxic ions of an endodontic tricalcium silicate-based sealer in local tissues and body organs.

BACKGROUND: This study aimed to track the toxic ions released by MTA Fillapex, BioRoot RCS, and an experimental tricalcium silicate-based sealer (CEO) into local and distant tissues as well as to investigate their potential adverse effects. In addition, the chemical constituents of the sealers were also evaluated. The main components of the dry powders, pastes, and mixed sealers were characterized. MATERIAL AND METHODS: Dry powder and sealer discs were each set for 72 h and their main components were characterized by energy dispersive X-ray spectroscopy. Polyethylene tubes filled with sealers were used to measure silicon and calcium ions. Polyethylene tubes filled with sealers or empty tubes were implanted into the dorsal connective tissue of Wistar rats. On days 7, 15, 30, and 45, the animals were euthanized and their brains, livers, kidneys, and subcutaneous tissues were removed and processed to determine the concentrations of chromium, cobalt, copper, lead, iron, magnesium and nickel using an inductively coupled plasma optical emission spectrometer. RESULTS: The main compounds in all sealers were carbon, oxygen, silicon, and calcium. MTA Fillapex release more Si while highest levels of Si were found in presence of BioRoot. The release of Si and Ca ions promoted by MTA Fillapex raise by time. No traces of cobalt, chromium, or magnesium were detected in any tissue. Irrespective of the sealer, no traces of copper and lead were found in the subcutaneous tissue; however, they were observed in the organs. The highest concentration of iron was identified in the liver. All sealers exhibited similar nickel traces in the brain, kidney, and liver except for MTA Fillapex, which demonstrated levels higher than CEO in the subcutaneous tissue on day 7. Tracing nickel ions over time revealed that lowest concentrations were found in subcutaneous tissue. CONCLUSION: Taken together, our data demonstrate that CEOs have chemical compositions similar to those of other commercial sealers. Furthermore, none of them exhibited a threat to systemic health. Moreover, the minimal amounts of iron and nickel detected were not related to the sealers.

Immediate and late systemic and lung effects of inhaled paraquat in rats.

The immediate and the late effects of inhaled Paraquat (PQ) on systemic and lung inflammation and oxidative stress were investigated. Rats were exposed to saline (control group) and two doses of inhaled PQ (27 and 54 mg/m3) and studied variables were measured: 1) one day after the end of PQ exposure as "immediate condition", 2) 16 days after the end of PQ exposure as "late condition". Total and differential white blood cells (WBC) counts, lipid peroxidation and nitrite were increased but thiol, superoxide dismutase and catalase in the blood and BALF as well as methacholine EC50 was reduced in both conditions in the animals exposed to PQ compared to control groups (p < 0. 05 to p < 0.001). Most studied parameters in the immediate condition were significantly higher than the late condition (p < 0.05 to p < 0.001). Systemic and lung inflammation and oxidative stress due to inhaled PQ in both the immediate and the late conditions were shown. Although most measured parameters in the immediate condition were higher, all variables were significantly different with the control group even in late condition, indicating a long-term effect of inhaled PQ toxicity, which may help in a more effective treatment of PQ poising in the future.

Intravitreal bevacizumab versus ranibizumab: Effects on the vessels of the fellow non-treated eye.

PURPOSE: To evaluate the effects of anti-vascular endothelial growth factors (anti-VEGF) on the vessels of the non-treated eyes following intravitreal injections. METHODS: In this prospective, non-randomized trial, a total of 38 patients were recruited. 21 patients received ranibizumab, and 17 patients received bevacizumab. Fundus photography was carried out at baseline immediately before injection and at 3 days, 7 days, and one month after the injections. Using image analysis software, measurements were summarized as the central retinal artery equivalent (CRAE) and central retinal vein equivalent. RESULTS: In non-treated eyes, CRAE decreased significantly from 153.23 ± 15.20 µm before injection to 148.77 ± 17.21 µm 3 days after intravitreal bevacizumab (P = 0.004). There was no significant difference in CRAE, between the pre-injection baseline, one week, and one month after intravitreal bevacizumab injection in non-treated eyes (P > 0.05). No significant difference was noted in CRAE in the non-treated eyes of the ranibizumab group at any post-injection visit (P = 0.1). CONCLUSION: A significant transient narrowing effect of bevacizumab on retinal arterioles in the fellow non-treated eyes on the third day after intravitreal injection may show that plasma concentrations of these drugs are sufficient to spread the effect to the other eye.

Reprogrammed endophytic microbial community in maize stalk induced by Trichoderma asperellum biocontrol agent against Fusarium diseases and mycotoxin accumulation.

Maize stalk rot and ear rot, caused by Fusarium graminearum and Fusarium verticillioides, respectively, are major diseases that threaten the sustainable production of maize. In this study, an artificial inoculation assay demonstrated that the control efficacy of maize stalk rot and ear rot by Trichoderma asperellum granules were 49.83 % and 39.63 %, respectively. By high-throughput sequencing of maize plants, a total of 76 196 ITS1 sequences and 887 226 V3V4 16S rRNA sequences were analyzed and were grouped into 2934 fungal and 24 248 bacterial operational taxonomic units (OTUs), respectively. It revealed a significantly higher endophytic microbial abundance in the stem tissue of plants grown in T. asperellum-treated soil than in those grown in the control, with the largest increase observed in the basal stem section. In addition, the endophytic microbial diversity and corresponding control effects all gradually decreased from the basal to apical parts of the stem in plants grown in Trichoderma-treated soil, indicating that Trichoderma stimulated a more significant effect on the defense system in the basal section of the stalk than in the apical parts of plants. Furthermore, the accumulation of deoxynivalenol (DON) and fumonisin B1 (FB1) decreased in the stem and ear of maize grown in T. asperellum-treated soil.