Adverse Physiological Effects Research Articles

Attenuation of Paraquat-Induced Nephrotoxicity and Dysfunction in Male Wistar Albino Rats

Background. Paraquat (PQ) is a pesticide commonly used in the control of weed in agricultural practices worldwide. Exposure to PQ has adverse biochemical and physiological consequences to humans and animals. The mechanism of toxicity is linked to the generation of reactive oxygen species and subsequent lipid peroxidation. Presently, no single effective antidote to PQ toxicity has been established. Therefore, the need to continually investigate different treatment approaches is of paramount importance. Objective. This study evaluated the capacity of selected dietary supplements to attenuate paraquat-induced kidney dysfunction and damages by determining some kidney function biomarkers and oxidative parameters. Methods. Thirty-six Wistar albino rats were randomly separated into six groups. Each group (except Normal control) was intoxicated every other day with 1.5 mg/kg body weight of PQ and four groups (except PQ and Normal control groups) were treated daily with 40 mg/kg of garlic, glutathione and vitamin C for two weeks. Results. The results showed significant ( p < 0.05) increases in concentration of kidney malondialdehyde, urea, creatinine, and blood lipid profiles. Also, significant decrease in concentrations of high-density lipoprotein cholesterol, kidney glutathione and total antioxidant capacity were presented by PQ control group compared to other PQ exposed groups treated with the antioxidant compounds. Conclusions. PQ-induced changes indicated kidney dysfunction and damage. However, the administration of antioxidant supplements attenuated the PQ-induced biochemical and physiological dysfunction in the rats.

Physiologic Effects of Nasal Aspiration and Nasopharyngeal Suctioning on Infants With Viral Bronchiolitis.

There is limited evidence supporting an optimum method for removing mucus from the airways of hospitalized infants with bronchiolitis. This study was designed to evaluate short-term physiologic effects between nasal aspiration and nasopharyngeal suctioning in infants. Sixteen infants requiring hospitalization for supportive management of bronchiolitis were instrumented with transcutaneously measured partial pressure of carbon dioxide ([Formula: see text]) and [Formula: see text] monitoring. Electrical impedance tomography (EIT) was used to estimate changes in inspiratory and end-expiratory lung volume loss and recovery. Subjects were suctioned with both nasal aspiration and nasopharyngeal suctioning methods in a randomized order (8 received nasal aspiration followed by nasopharyngeal suctioning, and 8 received nasophayrgeal suctioning followed by nasal aspiration). Noninvasive gas exchange and EIT measurements were obtained at baseline (pre-suction) and at 10, 20, and 30 min following each suctioning intervention. Sputum mass was obtained following suctioning, and clinical respiratory severity scores, before and after suctioning, were computed. There were no differences in inspiratory EIT (P = .93), change in end-expiratory lung impedance (ΔEELI; P = .53), [Formula: see text] (P = .41), [Formula: see text] (P = .88), heart rate (P = .31), or breathing frequency (P = .15) over the course of suctioning between nasal aspiration and nasopharyngeal suctioning. Sputum mass (P = .14) and clinical respiratory score differences before and after suctioning (P = .59) were not different between the 2 suctioning interventions. Sputum mass was not associated with ΔEELI at 30 min for nasal aspiration (ρ = 0.11, P = .69), but there was a moderate positive association for nasopharyngeal suctioning (ρ = 0.50, P = .048). Infants with viral bronchiolitis appeared to tolerate both suctioning techniques without adverse short-term physiologic effects, as indicated by the unchanged gas exchange and estimated lung volumes (EIT). Nasopharyngeal suctioning recovered 36% more sputum than did nasal aspiration and there was moderate correlation between sputum mass and end-expiratory lung impedance change at 30 minutes post-suction with nasopharyngeal that was not present with nasal aspiration. It is possible that a subset of patients may benefit from one type of suctioning over another. Future research focusing on important outcomes for suctioning patients with bronchiolitis with varying degrees of lung disease severity is needed.

Fentanyl impairs but ketamine preserves the microcirculatory response to hemorrhage.

Peripheral vasoconstriction is the most critical compensating mechanism following hemorrhage to maintain blood pressure. On the battlefield, ketamine rather than opioids is recommended for pain management in case of hemorrhage, but effects of analgesics on compensatory vasoconstriction are not defined. We hypothesized that fentanyl impairs but ketamine preserves the peripheral vasoconstriction and blood pressure compensation following hemorrhage. Sprague-Dawley rats (11-13 weeks) were randomly assigned to control (saline vehicle), fentanyl, or ketamine-treated groups with or without hemorrhage (n = 8 or 9 for each group). Rats were anesthetized with Inactin (i.p. 10 mg/100 g), and the spinotrapezius muscles were prepared for microcirculatory observation. Arteriolar arcades were observed with a Nikon microscope, and vessel images and arteriolar diameters were recorded by using Nikon NIS Elements Imaging Software (Nikon Instruments Inc. NY). After baseline perimeters were recorded, the arterioles were topically challenged with saline, fentanyl, or ketamine at concentrations relevant to intravenous analgesic doses to determine direct vasoactive effects. After arteriolar diameters returned to baseline, 30% of total blood volume was removed in 25 minutes. Ten minutes after hemorrhage, rats were intravenously injected with an analgesic dose of fentanyl (0.6 μg/100 g), ketamine (0.3 mg/100 g), or a comparable volume of saline. For each drug or vehicle administration, the total volume injected was 0.1 mL/100 g. Blood pressure, heart rate, and arteriolar responses were monitored for 40 minutes. Topical fentanyl-induced vasodilation (17 ± 2%), but ketamine caused vasoconstriction (-15 ± 4%, p < 0.01). Following hemorrhage, intravenous ketamine did not affect blood pressure or respiratory rate, while fentanyl induced a slight and transient (<5 minutes, p = 0.03 vs. saline group) decrease in blood pressure, with a profound and prolonged suppression in respiratory rate (>10 minutes, with a peak inhibition of 57 ± 8% of baseline, p < 0.01). The compensatory vasoconstriction observed after hemorrhage was not affected by ketamine treatment. However, after fentanyl injection, although changes in blood pressure were transiently present, arteriolar constriction to hemorrhage was absent and replaced with a sustained vasodilation (78 ± 25% to 36 ± 22% of baseline during the 40 minutes after injection, p < 0.01). Ketamine affects neither systemic nor microcirculatory compensatory responses to hemorrhage, providing preclinical evidence that ketamine may help attenuate adverse physiological consequences associated with opioids following traumatic hemorrhage. Microcirculatory responses are more sensitive than systemic response for evaluation of hemodynamic stability during procedures associated with pain management.

Mercury exposure in songbird communities within Sphagnum bog and upland forest ecosystems in the Adirondack Park (New York, USA).

Mercury (Hg) is a potent neurotoxin that biomagnifies within both aquatic and terrestrial food webs resulting in adverse physiological and reproductive effects on impacted wildlife populations, including songbird communities. Due to reducing conditions, wetland ecosystems promote the formation of methylmercury. Regional studies have documented elevated blood mercury concentrations in songbird species within these habitat types. The overall goal of this research was to examine spatial and seasonal patterns of Hg exposure for targeted songbird species within Sphagnum bog wetland systems and compare these patterns with adjacent upland forests in the Adirondack Park of New York State. Project sampling was conducted at study plots within four Sphagnum bog and associated upland forest sites from May - August during the 2008, 2009, and 2011 field seasons. The overall results documented: (1) blood Hg concentrations were elevated in songbird species inhabiting Sphagnum bog habitats as compared to nearby upland forest species; (2) target species within each habitat type exhibited consistent species-level patterns in blood Hg concentrations at each study site; and (3) no seasonal change in blood Hg concentrations within Sphagnum bog habitats was documented, but an increasing, followed by a decreasing seasonal pattern in mercury exposure was detected for upland forest species. Habitat type was demonstrated to influence avian Hg exposure levels. Moreover, Sphagnum bog ecosystems may be contributing to elevated Hg concentrations in biota within the surrounding environment. Seasonal patterns for blood Hg concentrations were found to vary between habitat type and are likely related to a combination of variables including habitat-driven Hg concentrations in prey items, seasonal dietary shifts, and annual molting cycles. This project emphasizes the importance of prioritizing future research efforts within identified high Hg habitat types, specifically wetland systems, to better characterize associated avian exposure levels, estimate the spatial extent of wetland systems on the surrounding environment, and identify locations of potential biological hotspots across the Adirondack Park.

Psycho-hormonal effects of aerobic fatigue on collegiate female soccer players

Up to 95% of a soccer match entails aerobic actions that may cause fatigue. Little is known about the effects of fatigue on the hormonal and psychological states of female players. Cortisol values (saliva sample), state anxiety (Spielberger State-trait Anxiety Inventory) and mood scores (Incredibly Short Profile of Mood States [ISP], comprising six subscales and total mood disturbances [TMD]) of 43 female players (aged 22.0±2.7 years) were taken immediately prior to and 15 min after an aerobic fatiguing test (AFT: Yo-Yo Intermittent Recovery [YYIR] test). Cortisol increased (d=0.7, p=0.007) and ISP–confusion and ISP–vigour decreased (d=0.5, p=0.01–0.02). At pre-AFT, a slight positive relationship between cortisol and anxiety-absence (r=0.3, p=0.05) was seen. TMD consistently demonstrated a strong relationship with all ISP and anxiety scores (r&gt;0.4, p&lt;0.01). Post-AFT results demonstrated a positive relationship between cortisol and blood lactate (r=0.3, p=0.04), between ISP–anger with maximal heart rate (r=0.3, p=0.03), ISP–anger and YYIR level as well as ISP–fatigue (r=0.4, p=0.04), and between perceived exertion rate and ISP–vigour (r=-0.4, p=0.008) as well as ISP–fatigue (r=0.3, p=0.05). Fatigue caused by prolonged activity may be a greater physiological than psychological stressor, although both may affect soccer performance. We recommend training players to increase their aerobic capacity to ensure maximal quality match-time before fatigue and its subsequent adverse physiological and psychological effects set in.&#x0D; Significance:&#x0D; &#x0D; The YYIR-1 test is effective in producing significant changes in both the hormonal and psychological states of female soccer players.&#x0D; Conditioning staff can effectively implement a mood state questionnaire to predict possible psychological stress (increase in state or trait anxiety) prior to and after a stressor.&#x0D; A relationship exists between cortisol and the absenteeism of anxiety prior to this fatiguing test, as well as with blood lactate thereafter. Therefore, the State-trait Anxiety Inventory questionnaire can be administered and blood lactate samples can be collected as they may display sensitive information regarding hormonal state.&#x0D; A positive relationship exists between the maximal heart rate achieved following an aerobic fatiguing test and various mood subscales experienced. Thus, with an increase in heart rate (as frequently observed due to fatigue), it can be assumed that an increase in perceived negative mood state might take place.&#x0D;

Effects of diluted bitumen exposure and recovery on the seawater acclimation response of Atlantic salmon smolts

Petrogenic chemicals are common and widespread contaminants in the aquatic environment. In Canada, increased extraction of bitumen from the oil sands and transport of the major crude oil export product, diluted bitumen (dilbit), amplifies the risk of a spill and contamination of Canadian waterways. Fish exposed to sublethal concentrations of crude oil can experience a variety of adverse physiological effects including osmoregulatory dysfunction. As regulation of water and ion balance is crucial during the seawater transition of anadromous fish, the hypothesis that dilbit impairs seawater acclimation in Atlantic salmon smolts (a fish at risk of exposure in Canada) was tested. Smolts were exposed for 24 d to the water-soluble fraction of dilbit in freshwater, and then transferred directly to seawater or allowed a 1 wk depuration period in uncontaminated freshwater prior to seawater transfer. The seawater acclimation response was quantified at 1 and 7 d post-transfer using established hematological, tissue, and molecular endpoints including gill Na+/K+-ATPase gene expression (nka). All smolts, irrespective of dilbit exposure, increased serum Na+ concentrations and osmolality within 1 d of seawater transfer. The recovery of these parameters to freshwater values by 7 d post-transfer was likely driven by the increased expression and activity of Na+/K+-ATPase in the gill. Histopathological changes in the gill were not observed; however, CYP1A-like immunoreactivity was detected in the pillar cells of gill lamellae of fish exposed to 67.9 μg/L PAC. Concentration-specific changes in kidney expression of a transmembrane water channel, aquaporin 3, occurred during seawater acclimation, but were resolved with 1 wk of depuration and were not associated with histopathological changes. In conclusion, apart from a robust CYP response in the gill, dilbit exposure did not greatly impact common measures of seawater acclimation, suggesting that significant osmoregulatory dysfunction is unlikely to occur if Atlantic salmon smolts are exposed sub-chronically to dilbit.

Sulfate nutrition improves short-term Al3+-stress tolerance in roots of Lolium perenne L

Trivalent aluminum ions (Al3+) in acidic soils are a major constraint for crop productivity inhibiting root elongation and promoting cell death. Al3+-toxicity has adverse biochemical and physiological effects on plant root growth. Sulfur is an essential macronutrient assimilated from the soil in the form of sulfate. However, the implication of sulfate nutritional status in the modulation of short-term Al3+-tolerance mechanisms in plant roots has not been previously reported. Here, we evaluated the effects of increased sulfate supply on short-term Al3+-toxicity in roots of Lolium perenne, measuring Al, Ca, Mg and S uptake, lipid peroxidation, total SOD activity, and transcriptional levels of Cu/Zn and Fe-SOD genes. First, the nitrogen sulfur ratio (N/S) in the TF nutrient solutions used in this study were computed to confirm that L. perenne plants were grown in sulfate deficiency (120 μM), optimal supply (240 μM), or overdoses conditions (360 μM), without affecting dry root biomass. Sulfate supplementation (>240 μM, and N/S ratio < 16) played a significant protection to Al3+-stress that prevents morphological changes in root tips, inhibits lipid peroxidation and differentially up-regulates total SOD activity, due changes in SOD gene expression. The results support the importance of sulfate nutritional status, on plant tissue homeostasis, enhancing the physiological tolerance mechanisms modulating lipid peroxidation damage induced by short-term Al3+-toxicity.

An analytic study on nonlinear radius change for hyperelastic tubular organs under volume expansion

Tubular organs with multilayers are common in human bodies and important for maintaining normal lives by transporting fluid, nutrient, or waste throughout the bodies. The inner layers of the organs are usually soft and can easily increase their volume under various adverse physiological effects such as edema and plaque growth. The volume expansion can also alter the stiffness of the organ tissues. The corresponding finite deformation of the tubular organs may significantly modify the size of the inner opening determining transportation capability. Deep understanding of the pattern of the luminal radius change is vital for treating related diseases incurred by the volume expansion. For this purpose, a two-layered tubular organ is modeled by generalized hyperelasticity, and the modeling is analyzed mathematically to more thoroughly demonstrate the nonlinear patterns of radius change under volume expansion and corresponding stiffness alteration. This article serves as an exemplary study for other tubular organs with more complicated structure and volume expansion characteristics.

Entero-atmospheric fistula migration: a new management alternative for complex septic open abdomen.

The open abdomen technique is a surgical strategy used in life-threatening conditions. After recognizing the morbidity and mortality attributed to abdominal compartment syndrome (ACS), several methods were developed to avoid this complication. The primary goal of temporary abdominal closure (TAC) is to create a tension-free closure of the abdomen without increasing intra-abdominal pressure. The optimal method of TAC should contain and protect the contents of the peritoneal cavity from external contamination and injury, preserve fascia; minimize desiccation and damage to viscera, remove and quantify third space fluid; prevent loss of domain, lower bacterial count, inflammatory response, keep the patient's abdominal wall skin dry and intact; preserve the integrity of the abdominal wall, be simple to perform and maintain, provide ease of reentry and have minimal adverse physiologic effects. Negative pressure wound therapy allowed the TAC method to achieve these objectives, but the presence of enteric fistulas or entero-atmospheric fistulas is still a challenge for even the most experienced surgeon. Here we describe two new alternatives to manage the septic complex abdomen with entero-atmospheric fistula.

Features of the mechanics of respiration and gas exchange during robot-assisted radical prostatectomy. Review

Introduction. Prostate cancer remains the most common urological malignancy, and robot-assisted radical prostatectomy (RARP) is the most effective treatment option. Special conditions for operation (Trendelenburg position and pneumoperitoneum) increase the airway pressure and reduce functional residual capacity of the lungs. Objectives. Review of risk factors for disorders and various interventions to improve pulmonary function and reduce the adverse physiological effects of RARP under general anesthesia. Materials and methods. This review of literature was conducted using the PubMed search engine in electronic databases Medline, Embase, the Cochrane Library and others up to May 2019. Results. A total of 22 studies were searched, including 9 randomized controlled trials. The factor that could worsen gas exchange during RARP was the body mass index &lt; 30 kg/m2. It is possible to improve gas exchange by means of recruitment maneuvers. Positive end-expiratory pressure of 5–10 cm H2O improves oxygenation but requires alertness in patients with chronic heart failure and chronic obstructive pulmonary disease. Conclusions. The main risk factors for perioperative respiratory and oxygenation disorders in RARP are pneumoperitoneum and steep Trendelenburg position. The effectiveness of ventilation regimes for the prevention of gas exchange disorders has not been proven. Using the recruitment maneuver and increasing the positive end-expiratory pressure does not improve the respiratory function of the lungs. Further studies with a longer follow-up period are needed to determine the clinical efficacy and safety of RARP.

Active emigration from climate change-caused seawater intrusion into freshwater habitats

Ecological risk assessment associated with seawater intrusions has been supported on the determination of lethal/sublethal effects following standard protocols that force exposure neglecting the ability of mobile organisms to spatially avoid salinized environments. Thus, this work aimed at assessing active emigration from climate change-caused seawater intrusion into freshwater habitats. To specific objectives were delineated: first, to compute median 12-h avoidance conductivities (AC50,12h) for freshwater species, and second, to compare it with literature data (LC50,48 or 96h, EC50,6 or 21d) to assess the relevance of the inclusion of stressor-driven emigration into risk assessment frameworks. Four standard test species, representing a broad range of ecological niches – Daphnia magna, Heterocypris incongruens, Danio rerio and Xenopus laevis – were selected. The salt NaCl was used as a surrogate of natural seawater to create the saline gradient, which was established in a 7-compartment system.At each specific LC50, 48 or 96h, the proportion of avoiders were well above 50%, ranging from 71 to 94%. At each LC50, considering also avoiders, populations would decline by 85–97%. Furthermore, for D. magna and X. laevis it was noticed that at the lowest conductivities eliciting mortality, the avoidance already exceeded 50%.The results showed that the emigration from salinity-disturbed habitats exists and that can even be more sensitive than standard endpoints. Looking solely to standard endpoints involving forced exposure may greatly underestimate the risk of local population extinction, because habitat function can be severely disrupted, with subsequent stressor-driven emigration, before any adverse physiological effects at the organism level. Thus, the present study highlights the need to include non-forced exposure testing into ecological risk assessment, namely of salinity-menaced costal freshwaters.

Health, Social and Economic Costs of Complex Treatment of Heroin Addiction

The use of drugs is a significant health and social problem worldwide. It gets increasingly complicated due to the emerging new challenges that give rise to concerns about public health. Besides the controlled use for medical purposes, around 250 million, (5.7%) of the world population aged 15-64 years, use illegal drugs. The opioid addiction is a mental and behavior disorder with complex bio-psycho-social genesis and chronic recidivistic course. One of the treatment methods is the so-called medication-assisted treatment that is performed by use of opiate agonists (methadone, etc.). Practically, this treatment means administration of the relevant medicine products in combination with a wide range of medical and rehabilitation services to alleviate the adverse medical, psychological and physiological effects that are inherent of opioid addiction. It is presented a good practice of a treatment methadone program by describing the organization of the Methadone Treatment Program at the Mental Health Center of Varna. It is presented an assessment of the effectiveness of the Program and its dynamics over the years as an expression of the health, social and economic costs of complex treatment of heroin addiction

A preliminary assessment of mercury in the feathers of migratory songbirds breeding in the North American subarctic.

Passerines appear to have a greater sensitivity to mercury than other avian orders, and little data exists for mercury exposure in songbirds breeding at high latitudes. In this preliminary study, we examined mercury exposure in 12 migratory songbird species breeding in Denali National Park & Preserve, in subarctic interior Alaska. Overall, we analyzed 343 feather samples collected in 2015-2017 for their total mercury content. Mercury levels found in feathers indicates exposure during the period of feather growth, which we assume largely took place on the breeding ground. In this limited sample of songbird feathers, mercury concentrations ranged from near zero to 6.34 μg/g. Most species sampled showed relatively low mercury, but some individuals had high enough concentrations to be subject to adverse physiological and behavioral effects. There was an indication that mercury concentrations of breeding songbirds may vary by diet composition, with non-invertivorous species possibly tending towards lower mercury concentrations. Overall, however, the degree of mercury exposure observed was low for songbirds breeding in the subarctic. Further examination would prove useful in clarifying mercury exposure and ecological relationships in this under-studied region.

Research on the resilience of Chinese nursing students to workplace vertical violence in clinical practice

This study aimed to explore the status and influencing factors of workplace vertical violence for Chinese nursing students, and examine the relationship between the resilience and workplace vertical violence. Questionnaire survey was conducted with cluster sampling among 486 nursing students by demographic questionnaire, the Resilience Scale of University Students and Questionnaire on Nursing Students' Workplace Vertical Violence. The survey indicated that, 51.23% of nursing students have experienced workplace vertical violence; 64.3% of perpetrators were identified as assigned nurses; 65.46% and 59.44% of nursing students have respectively suffered from adverse psychological and physiological effect; and 66.67% of nursing students determined to work harder and get stronger afterwards. Besides, birthplace, education level, professional identity, sensitive personality, prior knowledge of workplace vertical violence experience before clinical practice, and resilience were the most important influencing factors of workplace vertical violence for Chinese nursing students (p < 0.05). Workplace vertical violence suffering from nurses is very common for nursing students in the clinical training. Although it has negative impacts on the psychology and physiology of nursing students, more nursing students can positively adjust themselves. Resilience plays a positive role in the nursing students’ workplace vertical violence.

Environmental chemicals differentially affect epigenetic-related mechanisms in the zebrafish liver (ZF-L) cell line and in zebrafish embryos

A number of chemicals have been shown to affect epigenetic patterning and functions. Since epigenetic mechanisms regulate transcriptional networks, epigenetic changes induced by chemical exposure can represent early molecular events for long-term adverse physiological effects. Epigenetics has thus appeared as a research field of major interest within (eco)toxicological sciences. The present study aimed at measuring effects on epigenetic-related mechanisms of selected environmental chemicals (bisphenols, perfluorinated chemicals, methoxychlor, permethrin, vinclozolin and coumarin 47) in zebrafish embryos and liver cells (ZFL). Transcription of genes related to DNA methylation and histone modifications was measured and global DNA methylation was assessed in ZFL cells using the LUMA assay. The differences in results gathered from both models suggest that chemicals affect different mechanisms related to epigenetics in embryos and cells. In zebrafish embryos, exposure to bisphenol A, coumarin 47, methoxychlor and permethrin lead to significant transcriptional changes in epigenetic factors suggesting that they can impact early epigenome reprogramming related to embryonic development. In ZFL cells, significant transcriptional changes were observed upon exposure to all chemicals but coumarin 47; however, only perfluorooctane sulfonate induced significant effects on global DNA methylation. Notably, in contrast to the other tested chemicals, perfluorooctane sulfonate affected only the expression of the histone demethylase kdm5ba. In addition, kdm5ba appeared as a sensitive gene in zebrafish embryos as well. Taken together, the present results suggest a role for kdm5ba in regulating epigenetic patterns in response to chemical exposure, even though mechanisms remain unclear. To confirm these findings, further evidence is required regarding changes in site-specific histone marks and DNA methylation together with their long-term effects on physiological outcomes.

Further pharmacological comparison of d-methamphetamine and l-methamphetamine in rats: abuse-related behavioral and physiological indices

Previous preclinical research suggests that L-methamphetamine (L -MA) has potential therapeutic utility to treat psychostimulant abuse. This study examined potential abuse-related and adverse physiological effects of D -MA and L -MA alone and in combination in rats, as these effects had not been previously characterized. Potential abuse-related effects were examined in locomotor sensitization and conditioned place preference paradigms. Body temperature was monitored to assess the physiological effects of these drugs or drug combinations. In the locomotor study, D-MA induced locomotor sensitization to both D-MA and L -MA. L -MA induced locomotor sensitization only to D-MA. Responses to a combination of L-MA and D -MA were not differentially affected by L-MA or D-MA conditioning. In the conditioned place preference study, D-MA and L -MA each induced significant place preference. L -MA did not attenuate D-MA-induced place preference. In the body temperature study, D-MA induced hyperthermia and L -MA induced hypothermia. In combination, L -MA did not affect D-MA-induced hyperthermia. These data suggest that L -MA alone produces less abuse-related and adverse physiological effects than D-MA, but modulates and is modulated by concurrent and subsequent D-MA exposure, which may enhance the abuse liability of both drugs. These findings should be considered when L -MA is proposed for replacement therapy.

Identification and Quantification of 5-Fluoro ADB and the 5-Fluoro ADB Ester Hydrolysis Metabolite in Postmortem Blood Samples by LC-MS/MS.

5-Fluoro ADB, also known as 5-fluoro MDMB-PINACA, is a potent synthetic cannabinoid that is an agonist to the human cannabinoid CB1 and CB2 receptors. Adverse physiological and psychological effects that have resulted in hospitalization and/or death have been associated with 5-Fluoro ADB use. In addition, analytical confirmation of 5-Fluoro ADB use has been reported in both forensic human performance toxicology and postmortem cases. An analytical method for the identification and quantification of 5-fluoro ADB and the 5-fluoro ADB ester hydrolysis metabolite in human blood samples by liquid chromatography-tandem mass spectrometry was created and validated. The linear range of this assay was determined to be 0.01-10ng/mL for 5-fluoro ADB and 10-500ng/mL for the 5-fluoro ADB ester hydrolysis metabolite. The method met both precision and accuracy requirements. Endogenous and exogenous interferences were not observed. Ion suppression exceeding 25% was observed for 5-fluoro ADB. However, additional experiments were performed to ensure that the observed suppression did not affect other method validation parameters such as limit of detection and accuracy. Blood samples from 36 postmortem cases were analyzed utilizing this methodology. The average blood concentration of 5-fluoro ADB was 0.29ng/mL in central blood specimens and 0.05ng/mL in peripheral blood specimens. The average blood concentration of the 5-fluoro ADB ester hydrolysis metabolite was 49ng/mL in central blood specimens and 21ng/mL in peripheral blood specimens. A serum sample was also analyzed and had a serum concentration of 0.12ng/mL for 5-fluoro ADB and 42ng/mL for the 5-fluoro ADB ester hydrolysis metabolite. As the concentration of the 5-fluoro ADB ester hydrolysis metabolite was found at a greater concentration than that of 5-fluoro ADB, this metabolite may be a useful marker to monitor in an attempt to confirm 5-fluoro ADB use in toxicological investigations.

A mechanistic understanding of repellent function against mammalian herbivores

BackgroundBrowsing repellents are widely used to deter large herbivores from consuming plants of ecological, economic and aesthetic importance. Understanding how these repellents function on a behavioural mechanistic level is critical to predicting effectiveness. Here, we illustrate how these mechanisms can be tested, by exposing a model mammalian herbivore, the fallow deer, to different concentrations of a commercial chemical repellent (HaTe2) in two-choice feeding trials.ResultsThe repellent acted as a defensive chemical for the food by both reducing visitation and the amount consumed. Deer favoured the less defended feeders before ingesting any food, suggesting that the repellent altered olfactory and/or visual cues. Deer also consumed less of the more defended food when choosing between low and high repellent feeders than no and low repellent feeders, indicating that the repellent modified flavour and/or sensation. Repellent effectiveness declined with increased exposure, suggesting that consumption had no negative post-ingestive effects, and thus, deterrence was not caused by a conditioned aversion or irritation. Instead, this pattern suggests that deer learned, through repeated sampling of repellent-treated food, that there was no adverse physiological effect of ingesting it.ConclusionsThese results imply that HaTe2 repellent will not be effective over prolonged periods or in the absence of alternative untreated food. Understanding the mechanisms driving repellent function using two-choice trials could help practitioners decide whether a particular repellent is likely to be effective against mammalian herbivory in their management scenario.

Abstract 2914: Hexokinase 2-mediated metabolic reprogramming and apoptosis inhibition supports hepatocellular carcinoma radiation resistance

Abstract Purpose: Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by selectively upregulating hexokinase 2 (HK2), a key enzyme that catalyzes the first committed step of aerobic glycolysis, which provides genetic proof of concept that HK2 can be inhibited to treat HCC without adverse physiological consequences. The present study was designed to investigate the role of HK2-mediated metabolic reprogramming and apoptosis inhibition in radiation resistance of HCC cells. Experimental design: Acquired radiation-resistant cells were generated by sequential irradiation and recovery, and proteomics approach was used to illustrate the biological changes and molecular mechanisms involved. qRT-PCR was performed to evaluate the expression of glycolysis genes including HK2. TCGA and GEO analysis were used to investigate the prognostic value of HK2. Intrinsic radiation responsive and resistant HCC cells were also used to further identify the resistant role of HK2. Either lentivirus-mediated HK2 knockdown or pharmacological blockade by 3-bromopyruvate (BrPA) was used to inhibit HK2. Radiation resistance was evaluated by DNA damage response, in vitro cytotoxicity and colony formation assay. Apoptosis and ROS levels were measured with Annexin V and DC-FDA. Cytochrome c release and HK2 mitochondrial translocation were detected by immunofluorescence and western blots. 2-NBDG uptake, HK2 activity, lactate production, and 13C isotopomer tracing experiment were conducted to illustrate the glycolytic activities. HK2 translation efficiency was measured by polyribosome analysis. The upstream AKT-mTOR signaling were detected by western blots and rescued by pharmacological inhibitors. Xenografts were treated with radiation, BrPA, or a combination of radiation and BrPA. Results: Aerobic glycolysis was significantly activated and was indispensable for cell survival in both acquired and intrinsic radiation-resistant HCC cells. Mechanically, both up-regulation of mRNA expression of hexokinase (HK2) after sequential irradiation and increased translation of HK2 mRNA after one-fractional irradiation were mediated by the activation of AKT-mTOR axis. In addition, high HK2 expression was significantly associated with poor overall survival of HCC patients. Inhibition of HK2 expression or its mitochondrial translocation re-sensitized HCC cells to radiation therapy by promoting mitochondrial cytochrome c release and inhibiting of glycolysis both in vitro and in vivo. Conclusion: AKT-mTOR-HK2 axis plays crucial roles in both acquired and intrinsic radiation resistance of HCC cells by facilitating aerobic glycolysis and inhibiting cytochrome c release. Targeting HK2 could be an attractive and beneficial approach to improve the therapeutic effects of radiotherapy in HCC patients. Citation Format: Yuan Fang, Yizhi Zhan, Yiyi Li, Wei Wang, Dehua Wu, Yi Ding. Hexokinase 2-mediated metabolic reprogramming and apoptosis inhibition supports hepatocellular carcinoma radiation resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2914.

Physiological tolerance to drought under high temperature in soybean cultivars

Soybean is one of the most economically important crops and has experienced adverse physiological and biochemical effects when subjected to drought stress and heat, resulting in lost productivity. Thus, the objective of this work was to evaluate the physiological, metabolic and growth responses of well-watered and drought-treated soybean cultivars under high temperature. The experimental design was set up in randomized blocks, in a factorial scheme with three soybean cultivars (7739 M, Anta 82 and Desafio) and two water levels (100% and 40% field capacity). The experiment was conducted in a controlled growth chamber with a gradual rise in temperature at 41°C for 5 hours daily. Morpho-physiological and metabolic analyses were performed 12 days after the treatments imposition. The parameters of water and osmotic potentials, relative water content, photosynthetic rate, stomatal conductance, transpiratory rate, electron flux for the carboxylation and oxygenation of RuBisCO were decreased for all cultivars under water deficit and high temperature. The results showed that the photorespiration and the rate of electrolyte leakage were increased as well. These results showed that these physiological behaviors are standard for soybean plants under water deficit, regardless of cultivars. The cultivars 7739 M and Desafio showed lower performance than the cultivar Anta 82 for the parameters of total electron flow and effective quantum yield of PS II. The 7739 M and Anta 82 were the only cultivars to show increased non-photochemical quenching dissipation and total soluble sugar content, respectively, under stress conditions. Desafio cultivar demonstrated greater physiological and growth traits stability, which could potentially indicate double tolerance to these stresses.