Investigations on in vitro anti-carcinogenic potential of L-carnosine in liver cancer cells.

PubMed

Ding, Minghui; Jiao, Guihua; Shi, Haizhou; Chen, Yanrong

2018-02-01

This study was carried out to investigate the anti-carcinogenic effect of L-carnosine in human carcinoma cells (SNU-423). The SNU-423 cancer cells were cultured at a density of 2 × 10 4 cells/well in Dulbecco modified Eagle medium. After 24 h of adherence, the cells were treated with L-carnosine (0.2 and 1 mg/mL) for 48 h. Then, cell viability was assessed by sulforhodamine assay, while mitochondrial dysfunction was measured by fluorescence microscopy using chromatin-specific dye Hoechst 33258. Intracellular levels of ROS were assayed by fluorescence spectroscopy with 2',7'-dichlorofluorescein diacetate (DCFDA). L-Carnosine significantly inhibited the growth of the SNU-423 cells (p < 0.05). The inhibitory effect of L-carnosine was confirmed by results from mitochondrial fragmentation assay. The relative fluorescent unit was increased in a dose-dependent manner by L-carnosine, with values of 79.43, 186.87 and 400.89 for 0.6, 0.8 and 1 mg/mL of L-carnosine, respectively (p < 0.05). These results demonstrate that L-carnosine exerts anti-carcinogenic effects in human liver cancer cells.

Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to OGD/recovery.

PubMed

Ouyang, Li; Tian, Yueyang; Bao, Yun; Xu, Huijuan; Cheng, Jiaoyan; Wang, Bingyu; Shen, Yao; Chen, Zhong; Lyu, Jianxin

2016-06-01

Previously, we showed that carnosine upregulated the expression level of glutamate transporter 1 (GLT-1), which has been recognized as an important participant in the astrocyte-neuron lactate shuttle (ANLS), with ischemic model in vitro and in vivo. This study was designed to investigate the protective effect of carnosine on neuron/astrocyte co-cultures exposed to OGD/recovery, and to explore whether the ANLS or any other mechanism contributes to carnosine-induced neuroprotection on neuron/astrocyte. Co-cultures were treated with carnosine and exposed to OGD/recovery. Cell death and the extracellular levels of glutamate and GABA were measured. The mitochondrial respiration and glycolysis were detected by Seahorse Bioscience XF96 Extracellular Flux Analyzer. Results showed that carnosine decreased neuronal cell death, increased extracellular GABA level, and abolished the increase in extracellular glutamate and reversed the mitochondrial energy metabolism disorder induced by OGD/recovery. Carnosine also upregulated the mRNA level of neuronal glutamate transporter EAAC1 at 2h after OGD. Dihydrokainate, a specific inhibitor of GLT-1, decreased glycolysis but it did not affect mitochondrial respiration of the cells, and it could not reverse the increase in mitochondrial OXPHOS induced by carnosine in the co-cultures. The levels of mRNAs for monocarboxylate transporter1, 4 (MCT1, 4), which were expressed in astrocytes, and MCT2, the main neuronal MCT, were significantly increased at the early stage of recovery. Carnosine only partly reversed the increased expression of astrocytic MCT1 and MCT4. These results suggest that regulating astrocytic energy metabolism and extracellular glutamate and GABA levels but not the ANLS are involved in the carnosine-induced neuroprotection. Copyright © 2016 Elsevier Inc. All rights reserved.

Muscle Carnosine Concentration with the Co-Ingestion of Carbohydrate with β-alanine in Male Rats.

PubMed

Naderi, Alireza; Sadeghi, Mehdi; Sarshin, Amir; Imanipour, Vahid; Nazeri, Seyed Ali; Farkhayi, Fatemeh; Willems, Mark E T

2017-07-04

Muscle carnosine is an intracellular buffer. The intake of β-alanine, combined with carbohydrate and protein, enhanced carnosine loading in human muscle. The aim of the present study was to examine if muscle carnosine loading was enhanced by β-alanine intake and co-ingestion of glucose in male rats. Thirty-six male rats were divided into three groups and supplemented for four weeks: β-alanine (βA group, 1.8% β-alanine in drinking water), β-alanine and glucose (βAGL group, 1.8% β-alanine and 5% glucose in drinking water), and control (C group, drinking water). During the supplementation period, rats were exercised (20 m·min -1 , 10 min·day -1 , 4 days·week -1 for 4 weeks). Muscle carnosine concentration was quantified in soleus (n = 12) and rectus femoris (n = 6) muscles using high-performance liquid chromatography. In soleus muscle, carnosine concentration was 2.24 ± 1.10, 6.12 ± 1.08, and 6.93 ± 2.56 mmol/kg dw for control, βA, and βAGL, respectively. In rectus femoris, carnosine concentration was 2.26 ± 1.31, 7.90 ± 1.66, and 8.59 ± 2.33 mmol/kg dw for control, βA, and βAGL respectively. In each muscle, βA and βAGL resulted in similar carnosine increases compared to the control. In conclusion, β-alanine intake for four weeks, either alone or with glucose co-ingestion, equally increased muscle carnosine content. It appears that the potential insulin response to fluid glucose intake does not affect muscle carnosine loading in male rats.

Carnosine in the brain and olfactory system of amphibia and reptilia: a comparative study using immunocytochemical and biochemical methods.

PubMed

Artero, C; Martì, E; Biffo, S; Mulatero, B; Andreone, C; Margolis, F L; Fasolo, A

1991-09-16

The pattern of distribution of carnosine-like immunoreactivity and its relation to glial fibrillary acidic protein immunoreactivity have been studied in two lizards (Gallotia galloti and Tarentola delalandii) and in two anuran amphibians (Rana esculenta and Xenopus laevis) using immunocytochemical techniques. Biochemical data obtained by paper electrophoresis show that the dipeptides carnosine and homocarnosine are both present in the brain of all the species examined. In the central nervous system of both anurans and reptilians, carnosine immunoreactivity is localized in glial cells. An important species difference is, however, seen in the olfactory system since primary olfactory neurons and their processes extending to the olfactory bulb are carnosine positive in reptiles, whereas they are not immunostained in anurans. Thus, the cellular distribution of carnosine immunoreactivity in reptilians is very similar to that observed in birds and mammals and is distinct from that seen in amphibia.

Genetic parameters for carnitine, creatine, creatinine, carnosine, and anserine concentration in longissimus muscle and their association with palatability traits in Angus cattle.

PubMed

Mateescu, R G; Garmyn, A J; O'Neil, M A; Tait, R G; Abuzaid, A; Mayes, M S; Garrick, D J; Van Eenennaam, A L; VanOverbeke, D L; Hilton, G G; Beitz, D C; Reecy, J M

2012-12-01

The objective of this study was to estimate genetic parameters for carnitine, creatine, creatinine, carnosine, and anserine concentration in LM and to evaluate their associations with Warner-Bratzler shear force (WBSF) and beef palatability traits. Longissimus muscle samples from 2,285 Angus cattle were obtained and fabricated into steaks for analysis of carnitine, creatine, creatinine, carnosine, anserine, and other nutrients, and for trained sensory panel and WBSF assessments. Restricted maximum likelihood procedures were used to obtain estimates of variance and covariance components under a multiple-trait animal model. Estimates of heritability for carnitine, creatine, creatinine, carnosine, and anserine concentrations in LM from Angus cattle were 0.015, 0.434, 0.070, 0.383, and 0.531, respectively. Creatine, carnosine, and anserine were found to be moderately heritable, whereas almost no genetic variation was observed in carnitine and creatinine. Moderate positive genetic (0.25, P < 0.05) and phenotypic correlations (0.25, P < 0.05) were identified between carnosine and anserine. Medium negative genetic correlations were identified between creatine and both carnosine (-0.53, P < 0.05) and anserine (-0.46, P < 0.05). Beef and livery/metallic flavor were not associated with any of the 5 compounds analyzed (P > 0.10), and carnitine concentrations were not associated (P > 0.10) with any of the meat palatability traits analyzed. Carnosine was negatively associated with overall tenderness as assessed by trained sensory panelists. Similar negative associations with overall tenderness were identified for creatinine and anserine. Painty/fishy was the only flavor significantly and negatively associated with creatinine and carnosine. These results provide information regarding the concentration of these compounds, the amount of genetic variation, and evidence for negligible associations with beef palatability traits in LM of beef cattle.

Effects of dietary supplementation with carnosine on meat quality and antioxidant capacity in broiler chickens.

PubMed

Cong, J; Zhang, L; Li, J; Wang, S; Gao, F; Zhou, G

2017-02-01

1. This study aimed to investigate the effects of carnosine supplementation on meat quality, antioxidant capacity and lipid peroxidation status in broiler chickens. 2. A total of 256 1-d-old male Arbor Acres broilers were randomly assigned to 4 treatments consisting of 8 replicates of 8 chickens each. The birds were supplied with 4 different diets: a basal diet or a basal diet supplemented with 100, 200 or 400 mg/kg carnosine, respectively. The whole experiment lasted 42 d. 3. The results showed that dietary supplementation with carnosine linearly increased the values of pH 45   min and redness and reduced drip loss of breast meat. Dietary carnosine increased the activity of antioxidant enzymes in liver, serum and breast meat and decreased the contents of lipid peroxides at 21 and 42 d of age. 4. These findings indicated that dietary supplementation with carnosine was beneficial to enhance meat quality, antioxidant capacity and decrease lipid peroxidation status of breast meat.

L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

PubMed

Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

2012-01-01

The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health.

PubMed

Babizhayev, Mark A

2014-03-01

The increased oxidative stress in patients with smoking-associated disease, such as chronic obstructive pulmonary disease, is the result of an increased burden of inhaled oxidants as well as increased amounts of reactive oxygen species generated by various inflammatory, immune and epithelial cells of the airways. Nicotine sustains tobacco addiction, a major cause of disability and premature death. In addition to the neurochemical effects of nicotine, behavioural factors also affect the severity of nicotine withdrawal symptoms. For some people, the feel, smell and sight of a cigarette and the ritual of obtaining, handling, lighting and smoking a cigarette are all associated with the pleasurable effects of smoking. For individuals who are motivated to quit smoking, a combination of pharmacotherapy and behavioural therapy has been shown to be most effective in controlling the symptoms of nicotine withdrawal. In the previous studies, we proposed the viability and versatility of the imidazole-containing dipeptide-based compounds in the nutritional compositions as the telomere protection targeted therapeutic system for smokers in combination with in vitro cellular culture techniques being an investigative tool to study telomere attrition in cells induced by cigarette smoke (CS) and smoke constituents. Our working therapeutic concept is that imidazole-containing dipeptide-based compounds (non-hydrolyzed carnosine and carcinine) can modulate the telomerase activity in the normal cells and can provide the redox regulation of the cellular function under the terms of environmental and oxidative stress and in this way protect the length and the structure of telomeres from attrition. The detoxifying system of non-hydrolyzed carnosine or carcinine can be applied in the therapeutic nutrition formulations or installed in the cigarette filter. Patented specific oral formulations of non-hydrolyzed carnosine and carcinine provide a powerful manipulation tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection from telomere attrition associated with smoking. It is demonstrated in this work that both non-hydrolyzed carnosine and carcinine are characterized by greater bioavailability than pure l-carnosine subjected to enzymatic hydrolysis with carnosinase, and perform the detoxification of the α,β-unsaturated carbonyl compounds present in tobacco smoke. We argue that while an array of factors has shaped the history of the 'safer' cigarette, it is the current understanding of the industry's past deceptions and continuing avoidance of the moral implications of the sale of products that cause the enormous suffering and death of millions that makes reconsideration of 'safer' cigarettes challenging. In contrast to this, the data presented in the article show that recommended oral forms of non-hydrolyzed carnosine and carcinine protect against CS-induced disease and inflammation, and synergistic agents with the actions of imidazole-containing dipeptide compounds in developed formulations may have therapeutic utility in inflammatory lung diseases where CS plays a role.

Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

PubMed

de Courten, Barbora; Kurdiova, Timea; de Courten, Maximilian P J; Belan, Vitazoslav; Everaert, Inge; Vician, Marek; Teede, Helena; Gasperikova, Daniela; Aldini, Giancarlo; Derave, Wim; Ukropec, Jozef; Ukropcova, Barbara

2015-01-01

Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry), free-living ambulatory physical activity (accelerometers) and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years) with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58, p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity. Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

L-carnosine enhanced reproductive potential of the Saccharomyces cerevisiae yeast growing on medium containing glucose as a source of carbon.

PubMed

Kwolek-Mirek, Magdalena; Molon, Mateusz; Kaszycki, Pawel; Zadrag-Tecza, Renata

2016-08-01

Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine, which occurs in vertebrates, including humans. It has a number of favorable properties including buffering, chelating, antioxidant, anti-glycation and anti-aging activities. In our study we used the Saccharomyces cerevisiae yeast as a model organism to examine the impact of L-carnosine on the cell lifespan. We demonstrated that L-carnosine slowed down the growth and decreased the metabolic activity of cells as well as prolonged their generation time. On the other hand, it allowed for enhancement of the yeast reproductive potential and extended its reproductive lifespan. These changes may be a result of the reduced mitochondrial membrane potential and decreased ATP content in the yeast cells. However, due to reduction of the post-reproductive lifespan, L-carnosine did not have an influence on the total lifespan of yeast. In conclusion, L-carnosine does not extend the total lifespan of S. cerevisiae but rather it increases the yeast's reproductive capacity by increasing the number of daughter cells produced.

Antioxidant potential of date (Phoenix dactylifera L.) seed protein hydrolysates and carnosine in food and biological systems.

PubMed

Ambigaipalan, Priyatharini; Shahidi, Fereidoon

2015-01-28

Date seed protein hydrolysates were evaluated for antioxidant activity as well as solubility and water-holding capacity in food and biological model systems. Date seed protein hydrolysates as well as carnosine exhibited >80% of solubility over a pH range of 2-12. The hydrolysates and carnosine at 0.5% (w/w) were also found to be effective in enhancing water-holding capacity and cooking yield in a fish model system, which was nearly similar to sodium tripolyphosphate (STPP; 0.3%, w/w). Incorporation of hydrolysates (200 ppm) in fish model systems resulted in the highest inhibition (30%) of oxidation in comparison to butylated hydroxytoluene (BHT; 9%). In addition, hydrolysates and carnosine inhibited β-carotene oxidation by 75%. The hydrolysates (0.1 mg/mL) inhibited LDL cholesterol oxidation by 60%, whereas carnosine inhibited oxidation by 80% after 12 h of incubation. Additionally, hydrolysates and carnosine effectively inhibited hydroxyl (6 mg/mL) and peroxyl (0.1 mg/mL) radical-induced DNA scission. Therefore, date seed protein hydrolysates could be used as a potential functional food ingredient for health promotion.

Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme

PubMed Central

Wu, Josephine W.; Liu, Kuan-Nan; How, Su-Chun; Chen, Wei-An; Lai, Chia-Min; Liu, Hwai-Shen; Hu, Chaur-Jong; Wang, Steven S. -S.

2013-01-01

Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases. PMID:24349167

New glycoside derivatives of carnosine and analogs resistant to carnosinase hydrolysis: synthesis and characterization of their copper(II) complexes.

PubMed

Lanza, Valeria; Bellia, Francesco; D'Agata, Roberta; Grasso, Giuseppe; Rizzarelli, Enrico; Vecchio, Graziella

2011-02-01

Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide widely and abundantly distributed in muscle and nervous tissues of several animal species. Many functions have been proposed for this compound, such as antioxidant and metal ion-chelator properties. However, the main limitation on therapeutic use of carnosine on pathologies related to increased oxidative stress and/or metal ion dishomeostasis is associated with the hydrolysis by the specific dipeptidase carnosinase. Several attempts have been made to overcome this limitation. On this basis, we functionalized carnosine and its amide derivative with small sugars such as glucose and lactose. The resistance of these derivatives to the carnosinase hydrolysis was tested and compared with that of carnosine. We found that the glycoconjugation protects the dipeptide moiety from carnosinase hydrolysis, thus potentially improving the availability of carnosine. The copper(II) binding properties of all the new synthesized compounds were investigated by spectroscopic (UV-Visible and circular dichroism) and ESI-MS studies. Particularly, the new family of amide derivatives that are not significantly hydrolyzed by carnosinase is a very promising class of carnosine derivatives. The sugar moiety can act as a recognition element. These new derivatives are potentially able to act as chelating agents in the development of clinical approaches for the regulation of metal homeostasis in the field of medicinal inorganic chemistry. Copyright © 2010 Elsevier Inc. All rights reserved.

Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine

PubMed Central

Abdelkader, Hamdy; Longman, Michael R; Alany, Raid G; Pierscionek, Barbara

2016-01-01

This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380–450 nm, polydispersity index of 0.12–0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes. PMID:27366062

N-Acetylcarnosine and histidyl-hydrazide are potent agents for multitargeted ophthalmic therapy of senile cataracts and diabetic ocular complications.

PubMed

Babizhayev, Mark A; Guiotto, Andrea; Kasus-Jacobi, Anne

2009-01-01

In human diabetes, the deleterious effects of chronic hyperglycemia are the result of excessive nonenzymatic modification of proteins and phospholipids by glucose and its by-products leading to the formation of irreversible oxidized, aromatic, and fluorescent ligands known as advanced glycation end products. This glycation process has been associated with deleterious health effects. The present invention provides the potent inhibitors of protein glycation and AGEs formation, which are particularly advantageous for eyedrop delivery in the prevention and treatment of diabetes- and age-related pathologies. We proposed a deglycation system involving removal, by transglycation of sugar or aldehyde moieties from the Schiff bases by ophthalmic aldehyde scavenger L-carnosine derived from its ocular bioactivating sustained release prodrug 1% N-acetylcarnosine (NAC) lubricant eyedrops containing a mucoadhesive cellulose compound combined with corneal absorption promoters in drug delivery system. Carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and patented in ophthalmic formulations with NAC bioactivating prodrug to moderate the enzymatic hydrolysis of a dipeptide by carnosinase (inhibited by a nonhydrolyzable substrate analog so that this keeps steadier levels of the drug active principle in the aqueous humor). Leucyl-histidylhydrazide peptidomimetic demonstrated the transglycation activity more pronounced than L-carnosine accounting for the ability of either molecule to reverse pre-existing, glycation-induced, cross-linking, and checking the nonenzymatic glycation cascade in the ophthalmic pathologies. The ophthalmic drug N-acetylcarnosine eye drop formulation with sustained time- release and increased absorption of L-carnosine in the aqueous humor (a prolonged effective dose) showed follow-up treatment efficacy for age-related cataracts for enrolled patients into the randomized double blind placebo controlled crossover clinical trial, and in over 50250 various cohort patients, was demonstrated to have an efficacy, safety and good tolerability for prevention and treatment of visual impairment in the older population data base. The bioactivating antioxidant NAC and histidyl-hydrazide are potent agents with the pleiotropic effects for ophthalmic therapy of senile cataracts and diabetic ocular complications.

On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

PubMed Central

Alany, Raid G.

2016-01-01

Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation. PMID:27822337

An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2015-01-01

Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the oral supplement by athletes to achieve the fine sporting art results due to the buffering activities of carnosine and its related imidazole- containing compounds which contribute to the maintenance of the acid-base balance in the acting muscles. This work originally emphasizes that overall data indicate the signaling activities of carnosine in skeletal and cardiac muscles switching on the mechanisms of exercise-induced telomere protection and point to the stress response and growth/cellular proliferation pathways as high-priority candidates for the ongoing studies and therapeutic concepts. The therapeutic interventions utilizing the specific oral formulation (Can-C Plus), timing dosing and pharmaco-nutritional boost of imidazolecontaining dipeptides can maintain health, enhance physical exercise performance and prevent aging. The patented therapeutic concept protects the existence of the interesting physiological major activities, better controls and therapeutic treatments for aging/age-related disorders (including age-related loss of muscle mass and muscle function) using carnosine dipeptide for cellular rejuvenation and manipulating telomeres and enzyme telomerase activity that may reduce some of the physiological declines that accompany aging.

Computational design of bio-inspired carnosine-based HOBr antioxidants

NASA Astrophysics Data System (ADS)

Sarrami, Farzaneh; Yu, Li-Juan; Karton, Amir

2017-10-01

During a respiratory burst the enzyme myeloperoxidase generates significant amounts of hypohalous acids (HOX, X = Cl and Br) in order to inflict oxidative damage upon invading pathogens. However, excessive production of these potent oxidants is associated with numerous inflammatory diseases. It has been suggested that the endogenous antioxidant carnosine is an effective HOCl scavenger. Recent computational and experimental studies suggested that an intramolecular Cl+ transfer from the imidazole ring to the terminal amine might play an important role in the antioxidant activity of carnosine. Based on high-level ab initio calculations, we propose a similar reaction mechanism for the intramolecular Br+ transfer in carnosine. These results suggest that carnosine may be an effective HOBr scavenger. On the basis of the proposed reaction mechanism, we proceed to design systems that share similar structural features to carnosine but with enhanced HOX scavenging capabilities for X = Cl and Br. We find that (i) elongating the β-alanyl-glycyl side chain by one carbon reduces the reaction barriers by up to 44%, and (ii) substituting the imidazole ring with strong electron-donating groups reduces the reaction barriers by similar amounts. We also show that the above structural and electronic effects are largely additive. In an antioxidant candidate that involves both of these effects the reaction barriers are reduced by 71%.

Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock

PubMed Central

Sahin, Sabiha; Donmez, Dilek Burukoglu

2018-01-01

Background Acute kidney injury (AKI) secondary to sepsis is a major cause of morbidity and mortality in the human intensive care unit (ICU). Kidney function and the histological findings of AKI were investigated in an experimental rat model with sepsis induced by cecal ligation and puncture (CLP) and compared with and without treatment with carnosine (beta-alanyl-L-histidine). Material/Methods Twenty-four Sprague-Dawley rats were randomly divided into three groups consisting eight rats in each: Group 1 – control; Group 2 – septic shock; and Group 3 – septic shock treated with carnosine. Femoral vein and artery catheterization were applied in all rats. Rats in Group 1 underwent laparotomy and catheterization. The other two groups with septic shock underwent laparotomy, CLP, catheterization, and bladder cannulation. Rats in Group 3 received an intraperitoneal (IP) injection of 250 mg/kg carnosine, 60 min following CLP. Rats were monitored for blood pressure, pulse rate, and body temperature to assess responses to postoperative sepsis, and 10 mL/kg saline replacement was administered. Twenty-four hours following CLP, rats were sacrificed, and blood and renal tissue samples were collected. Results Statistically significant improvements were observed in kidney function, tissue and serum malondialdehyde levels, routine blood values, biochemical indices, and in histopathological findings in rats in Group 3 who were treated with carnosine, compared with Group 2 exposed to septic shock without carnosine treatment. Conclusions Carnosine (beta-alanyl-L-histidine) has been shown to have beneficial effects in reducing AKI due to septic shock in a rat model of septicemia. PMID:29334583

Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

PubMed

Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

2004-03-01

Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (P<0.001), but a slight increase in coenzyme Q(10). There was also a four-fold increase in creatinine, presumably due to its formation from creatine. It is concluded that biologically, and possibly nutritionally, significant levels of taurine, carnosine, coenzyme Q(10), and creatine are present in beef and lamb, but that these levels vary between muscles, between animals, and with cooking.

Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury

PubMed Central

Wang, Cunlian; Zhang, Ruihua; Xu, Mingju; Liu, Baojian; Wei, Dong; Wang, Guohua; Tian, Shufei

2015-01-01

Oxidative stress injury is an important pathogenesis of influenza virus in critically ill patients. The present study investigated the efficacy of carnosine, an antioxidant and free radical scavenger, on a model of acute lung injury (ALI) induced by H9N2 swine influenza virus. Female specific-pathogen-free BALB/c mice were randomized into four groups and treated as follows: (1) H9N2 group, (2) mock control group, (3) H9N2+carnosine group and (4) carnosine control group. The H9N2 group mice were inoculated intranasally with A/Swine/Hebei/012/2008/ (H9N2) virus (100 μl) in allantoic fluid (AF), whilst mock-infected animals were intranasally inoculated with non-infectious AF. Carnosine [10 mg (kg body mass)− 1] was administered orally (100 μl) for 7 days consecutively. The survival rate, lung water content, TNF-α and IL-1β levels, lung histopathology, myeloperoxidase (MPO) activity, and Toll-like receptor (TLR)-4 levels were determined at 2, 4, 6, 8 and 14 days after inoculation. Carnosine treatment effectively decreased the mortality (43 versus 75 %, P < 0.05), significantly ameliorated pathological lesions in lungs and decreased the lung wet/dry mass ratio (P < 0.05). It also inhibited MPO activity, suppressed TNF-α and IL-1β release, decreased the H9N2 viral titre, and markedly inhibited levels of TLR-4 mRNA and protein in the lungs of infected mice (P < 0.05), which supported the use of carnosine for managing severe influenza cases. PMID:26233716

Effect of a zinc L-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo.

PubMed

Hill, Tracy L; Blikslager, Anthony T

2012-05-01

To examine whether a zinc L-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa. Gastric mucosa from 6 healthy dogs. Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc L-carnosine compound, or zinc L-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti-active caspase-3 antibody as an indicator of apoptosis. Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc L-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc L-carnosine compound did not protect against development of apoptosis. Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc L-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.

Ergogenic Effects of β-Alanine and Carnosine: Proposed Future Research to Quantify Their Efficacy

PubMed Central

Caruso, John; Charles, Jessica; Unruh, Kayla; Giebel, Rachel; Learmonth, Lexis; Potter, William

2012-01-01

β-alanine is an amino acid that, when combined with histidine, forms the dipeptide carnosine within skeletal muscle. Carnosine and β-alanine each have multiple purposes within the human body; this review focuses on their roles as ergogenic aids to exercise performance and suggests how to best quantify the former’s merits as a buffer. Carnosine normally makes a small contribution to a cell’s total buffer capacity; yet β-alanine supplementation raises intracellular carnosine concentrations that in turn improve a muscle’s ability to buffer protons. Numerous studies assessed the impact of oral β-alanine intake on muscle carnosine levels and exercise performance. β-alanine may best act as an ergogenic aid when metabolic acidosis is the primary factor for compromised exercise performance. Blood lactate kinetics, whereby the concentration of the metabolite is measured as it enters and leaves the vasculature over time, affords the best opportunity to assess the merits of β-alanine supplementation’s ergogenic effect. Optimal β-alanine dosages have not been determined for persons of different ages, genders and nutritional/health conditions. Doses as high as 6.4 g day−1, for ten weeks have been administered to healthy subjects. Paraesthesia is to date the only side effect from oral β-alanine ingestion. The severity and duration of paraesthesia episodes are dose-dependent. It may be unwise for persons with a history of paraesthesia to ingest β-alanine. As for any supplement, caution should be exercised with β-alanine supplementation. PMID:22852051

Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

NASA Astrophysics Data System (ADS)

Özdemir, Mahir S.; Reyngoudt, Harmen; DeDeene, Yves; Sazak, Hakan S.; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

2007-12-01

Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pHi range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy (1H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

L-carnosine modulates respiratory burst and reactive oxygen species production in neutrophil biochemistry and function: may oral dosage form of non-hydrolized dipeptide L-carnosine complement anti-infective anti-influenza flu treatment, prevention and self-care as an alternative to the conventional vaccination?

PubMed

Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

2014-05-01

Influenza A is a viral disease of global dimension, presenting with high morbidity and mortality in annual epidemics, and in pandemics which are of infrequent occurrence but which have very high attack rates. Influenza vaccines of the future must be directed toward use of conserved group-specific viral antigens, such as are present in transitional proteins which are exposed during the fusion of virus to the host cell. Influenza probes revealed a continuing battle for survival between host and parasite in which the host population updates the specificity of its pool of humoral immunity by contact with and response to infection with the most recent viruses which possess altered antigenic specificity in their hemagglutinin (HA) ligand. It is well known that the HA protein is found on the surface of the influenza virus particle and is responsible for binding to receptors on host cells and initiating infection. Polymorphonuclear neutrophils (PMN) have been reported to be involved in the initial host response to influenza A virus (IAV). Early after IAV infection, neutrophils infiltrate the airway probably due to release of chemokines that attract PMN. Clearly, severe IAV infection is characterized by increased neutrophil influx into the lung or upper respiratory tract. Carnosine (β-alanyl-L-histidine) and anserine (N-β-alanyl-1-methyl-L-histidine) are found in skeletal muscle of most vertebrates, including those used for food; for example, 100 g of chicken breast contains 400 mg (17.6 mmol/L) of carnosine and 1020 mg (33.6 mmol/l) of anserine. Carnosine-stimulated respiratory burst in neutrophils is a universal biological mechanism of influenza virus destruction. Our own studies revealed previously unappreciated functional effects of carnosine and related histidine containing compounds as a natural biological prevention and barrier against Influenza virus infection, expand public understanding of the antiviral properties of imidazole-containing dipeptide based compounds, and suggest important interactions between neutrophills and carnosine related compounds in the host response to viruses and bacteria. Carnosine and anserine were also found to reduce apoptosis of human neutrophils. In this way these histidine-containing compounds can modulate the Influenza virus release from neutrophills and reduce virus dissemination through the body of the organism. This review points the ability of therapeutic control of Influenza viral infections associated with modulation by oral nonhydrolized forms of carnosine and related histidine-containg compounds of PMN apoptosis which may be involved at least in part in the pathophysiology of the disease in animals and humans. The data presented in this article, overall, may have implications for global influenza surveillance and planning for pandemic influenza therapeutic prevention with oral forms of non-hydrolized natural L-carnosine as a suitable alternative to the conventional vaccination for various flu ailments.

Role of beta-alanine supplementation on muscle carnosine and exercise performance.

PubMed

Artioli, Guilherme Giannini; Gualano, Bruno; Smith, Abbie; Stout, Jeffrey; Lancha, Antonio Herbert

2010-06-01

In this narrative review, we present and discuss the current knowledge available on carnosine and beta-alanine metabolism as well as the effects of beta-alanine supplementation on exercise performance. Intramuscular acidosis has been attributed to be one of the main causes of fatigue during intense exercise. Carnosine has been shown to play a significant role in muscle pH regulation. Carnosine is synthesized in skeletal muscle from the amino acids l-histidine and beta-alanine. The rate-limiting factor of carnosine synthesis is beta-alanine availability. Supplementation with beta-alanine has been shown to increase muscle carnosine content and therefore total muscle buffer capacity, with the potential to elicit improvements in physical performance during high-intensity exercise. Studies on beta-alanine supplementation and exercise performance have demonstrated improvements in performance during multiple bouts of high-intensity exercise and in single bouts of exercise lasting more than 60 s. Similarly, beta-alanine supplementation has been shown to delay the onset of neuromuscular fatigue. Although beta-alanine does not improve maximal strength or VO2max, some aspects of endurance performance, such as anaerobic threshold and time to exhaustion, can be enhanced. Symptoms of paresthesia may be observed if a single dose higher than 800 mg is ingested. The symptoms, however, are transient and related to the increase in plasma concentration. They can be prevented by using controlled release capsules and smaller dosing strategies. No important side effect was related to the use of this amino acid so far. In conclusion, beta-alanine supplementation seems to be a safe nutritional strategy capable of improving high-intensity anaerobic performance.

Identification and characterisation of carnostatine (SAN9812), a potent and selective carnosinase (CN1) inhibitor with in vivo activity.

PubMed

Qiu, Jiedong; Hauske, Sibylle J; Zhang, Shiqi; Rodriguez-Niño, Angelica; Albrecht, Thomas; Pastene, Diego O; van den Born, Jacob; van Goor, Harry; Ruf, Sven; Kohlmann, Markus; Teufel, Michael; Krämer, Bernhard K; Hammes, Hans-Peter; Peters, Verena; Yard, Benito A; Kannt, Aimo

2018-06-20

Carnosinase 1 (CN1) has been postulated to be a susceptibility factor for developing diabetic nephropathy (DN). Although its major substrate, carnosine, is beneficial in rodent models of DN, translation of these findings to humans has been hampered by high CN1 activity in human serum resulting in rapid degradation of carnosine. To overcome this hurdle, we screened a protease-directed small-molecule library for inhibitors of human recombinant CN1. We identified SAN9812 as a potent and highly selective inhibitor of CN1 activity with a K i of 11 nM. It also inhibited CN1 activity in human serum and serum of transgenic mice-overexpressing human CN1. Subcutaneous administration of 30 mg/kg SAN9812 led to a sustained reduction in circulating CN1 activity in human CN1 transgenic (TG) mice. Simultaneous administration of carnosine and SAN9812 increased carnosine levels in plasma and kidney by up to 100-fold compared to treatment-naïve CN1-overexpressing mice. To our knowledge, this is the first study reporting on a potent and selective CN1 inhibitor with in vivo activity. SAN9812, also called carnostatine, may be used to increase renal carnosine concentration as a potential therapeutic modality for renal diseases linked to glycoxidative conditions.

Effects of carnosine supplementation to an all-plant protein diet for rainbow trout(Oncorhynchus mykiss)

USDA-ARS?s Scientific Manuscript database

Fish meal may contain “unknown growth factors” that have yet to be identified for their physiological role. Carnosine is a histidine-ß-alanine dipeptide found in muscle and nervous system tissue which has been demonstrated to have biological activity, but its physiological role is not well defined. ...

Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

PubMed

Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

2015-12-01

The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

PubMed

Banerjee, Soumyabrata; Poddar, Mrinal K

2015-03-01

Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

PubMed

Banerjee, S; Poddar, M K

2016-04-05

Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.

PubMed

Blancquaert, Laura; Baguet, Audrey; Bex, Tine; Volkaert, Anneke; Everaert, Inge; Delanghe, Joris; Petrovic, Mirko; Vervaet, Chris; De Henauw, Stefaan; Constantin-Teodosiu, Dumitru; Greenhaff, Paul; Derave, Wim

2018-04-01

Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily β-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (P<0·001) and gastrocnemius (P=0·001) muscle. To conclude, the body creatine pool declined over a 3-month vegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

PubMed Central

Hobson, Ruth M; Artioli, Guilherme G.; Otaduy, Maria C.; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S. Painelli, Vitor; Harris, Roger C.; Gualano, Bruno

2015-01-01

Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists. PMID:25875297

Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury.

PubMed

Russo, Rossella; Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

2015-01-01

Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, homotaurine, and L-carnosine were intravitreally injected and RGC survival evaluated following retrograde labeling with FluoroGold. Total and phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) protein levels, as well as calpain activity, were analyzed with western blot. Protein kinase A (PKA) was inhibited by intravitreal injection of H89. A synergic neuroprotective effect on RGC survival was observed following the combined treatment with forskolin, homotaurine, and L-carnosine compared to forskolin alone. The observed neuroprotection was associated with reduced calpain activity, upregulation of phosphoinositide 3-kinase (PI3K)/Akt pathway, and inhibition of GSK-3β but was independent from PKA activation and distinct from the hypotensive effects of forskolin. A multidrug/multitarget approach, by interfering with several pathways involved in RGC degeneration, may be promising to achieve glaucoma neuroprotection.

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

PubMed

Solis, Marina Yazigi; Cooper, Simon; Hobson, Ruth M; Artioli, Guilherme G; Otaduy, Maria C; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S Painelli, Vitor; Harris, Roger C; Gualano, Bruno; Sale, Craig

2015-01-01

Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P < 0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

l-Carnosine as Adjunctive Therapy in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Ghajar, Alireza; Aghajan-Nashtaei, Farinaz; Afarideh, Mohsen; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

2018-06-01

This study aimed to investigate the efficacy and tolerability of l-carnosine as an add-on to methylphenidate in management of children with attention-deficit/hyperactivity disorder (ADHD). This was an 8-week, randomized, double-blind placebo-controlled study. Fifty-six drug-free children and adolescents aged 6-17 years old with a diagnosis of ADHD entered the study. The patients were randomly assigned to l-carnosine (800 mg/d in two divided doses) or placebo plus methylphenidate (0.5-1.5 mg/kg/d) for 8 weeks. Children were assessed using the Teacher and Parent ADHD Rating Scale-IV (ADHD-RS-IV) at baseline and at weeks 4 and 8 postbaseline. Fifty patients completed the study, and all had two postbaseline measurements. Using the general linear model repeated measures, significant effect was observed for time × treatment interaction on total and inattention subscales of the Parent ADHD-RS (Greenhouse-Geisser corrected: F = 3.783, df = 1.444, p = 0.041 and F = 4.032, df = 1.600, p = 0.030). Improvements in the Teacher ADHD-RS were not significantly different between the two groups in total (Greenhouse-Geisser corrected: F = 0.200, df = 1.218, p = 0.705), as well as inattention and hyperactivity subscale scores (p = 0.956 and 0.281, respectively). The frequency of side effects was not significantly different between the two treatment arms. l-carnosine, as a supplementary medication, might be beneficial in treatment of children with ADHD. However, further investigations and different doses of l-carnosine are required to replicate these findings in children with ADHD.

Hydrophilic chromatographic determination of carnosine, anserine, balenine, creatine, and creatinine.

PubMed

Mora, Leticia; Sentandreu, Miguel Angel; Toldrá, Fidel

2007-06-13

A new HPLC procedure based on hydrophilic interaction chromatography (HILIC) has been developed for the simultaneous determination of carnosine, anserine, balenine, creatine, and creatinine in meat. This is the first time that HILIC has been directly applied to the study of meat components, having the advantage of not requiring complex cleanup and/or sample derivatization procedures. The chromatographic separation has been developed using a silica column (4.6 x 150 mm, 3 microm), and the proposed methodology is simple, reliable, and fast (<13 min per sample). The method has been validated in terms of linearity, repeatability, reproducibility, and recovery and represents an interesting alternative to methods currently in use for determining the mentioned compounds and other polar substances. The detection limits are 5.64, 8.23, 3.66, 3.99, and 0.06 microg/mL for carnosine, anserine, balenine, creatine, and creatinine, respectively.

l-Carnosine As an Adjunctive Therapy to Risperidone in Children with Autistic Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Hajizadeh-Zaker, Reihaneh; Ghajar, Alireza; Mesgarpour, Bita; Afarideh, Mohsen; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

2018-02-01

This study aimed at investigating the efficacy and tolerability of l-carnosine as an add-on to risperidone in the management of children with autism. This was a 10-week, randomized, double-blind, placebo-controlled study. Seventy drug-free children aged 4-12 years old with a diagnosis of autism spectrum disorder (ASD), according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. (DSM-5) who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of ≥12, entered the study. The patients were randomly assigned to l-carnosine (800 mg/day in 2 divided doses) or placebo in addition to risperidone titrated up to 2 mg/day (based on body weight) for 10 weeks. The children were assessed by using ABC-C at baseline and weeks 5 and 10 post-baseline. The primary outcome measure was the mean change in the ABC-C irritability subscale score, and other subscale scores were defined as secondary outcomes. Using the general linear model repeated measures, no significant effect was observed for time × treatment interaction on the irritability subscale scores. However, significant effect was detected on the hyperactivity/noncompliance subscale [F (1.62, 64.96) = 3.53, p-value = 0.044]. No significant improvements were obtained on the lethargy/social withdrawal, stereotypic behavior, and inappropriate speech subscale scores. Significantly greater score reduction in the hyperactivity/noncompliance subscale occurred in the l-carnosine group compared with the placebo group at the end of the trial. Extrapyramidal Symptom Rating Scale Scores and its changes did not differ between the two groups. The frequency of other side effects was not significantly different between the two groups. Although no significant difference was detected on the irritability subscale scores, l-carnosine add-on can improve hyperactivity/noncompliance subscales of the ABC-C rating scale in patients with ASD.

Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury

PubMed Central

Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

2015-01-01

Purpose Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Methods Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, homotaurine, and L-carnosine were intravitreally injected and RGC survival evaluated following retrograde labeling with FluoroGold. Total and phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) protein levels, as well as calpain activity, were analyzed with western blot. Protein kinase A (PKA) was inhibited by intravitreal injection of H89. Results A synergic neuroprotective effect on RGC survival was observed following the combined treatment with forskolin, homotaurine, and L-carnosine compared to forskolin alone. The observed neuroprotection was associated with reduced calpain activity, upregulation of phosphoinositide 3-kinase (PI3K)/Akt pathway, and inhibition of GSK-3β but was independent from PKA activation and distinct from the hypotensive effects of forskolin. Conclusions A multidrug/multitarget approach, by interfering with several pathways involved in RGC degeneration, may be promising to achieve glaucoma neuroprotection. PMID:26167113

[Effects of ß-alanine supplementation on athletic performance].

PubMed

Domínguez, Raúl; Hernández Lougedo, Juan; Maté-Muñoz, José Luis; Garnacho-Castaño, Manuel Vicente

2014-10-06

Carnosine, dipeptide formed by amino acids ß-alanine and L-histidine, has important physiological functions among which its antioxidant and related memory and learning. However, in connection with the exercise, the most important functions would be associated with muscle contractility, improving calcium sensitivity in muscle fibers, and the regulatory function of pH. Thus, it is proposed that carnosine is the major intracellular buffer, but could contribute to 7-10% in buffer or buffer capacity. Since carnosine synthesis seems to be limited by the availability of ß-alanine supplementation with this compound has been gaining increasing popularity among the athlete population. Therefore, the objective of this study literature review was to examine all those research works have shown the effect of ß-alanine supplementation on athletic performance. Moreover, it also has attempted to establish a specific dosage that maximizing the potential benefits, minimize paresthesia, the main side effect presented in response to supplementation. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Advanced drug delivery of N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine), carcinine (beta-alanylhistamine) and L-carnosine (beta-alanyl-L-histidine) in targeting peptide compounds as pharmacological chaperones for use in tissue engineering, human disease management and therapy: from in vitro to the clinic.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2010-11-01

A pharmacological chaperone is a relatively new concept in the treatment of certain chronic disabling diseases. Cells maintain a complete set of functionally competent proteins normally and in the face of injury or environmental stress with the use of various mechanisms, including systems of proteins called molecular chaperones. Proteins that are denatured by any form of proteotoxic stress are cooperatively recognized by heat shock proteins (HSP) and directed for refolding or degradation. Under non-denaturing conditions HSP have important functions in cell physiology such as in transmembrane protein transport and in enabling assembly and folding of newly synthesized polypeptides. Besides cellular molecular chaperones, which are stress-induced proteins, there have been recently reported chemical, or so-called pharmacological chaperones with demonstrated ability to be effective in preventing misfolding of different disease causing proteins, specifically in the therapeutic management of sight-threatening eye diseases, essentially reducing the severity of several neurodegenerative disorders (such as age-related macular degeneration), cataract and many other protein-misfolding diseases. This work reviews the biological and therapeutic activities protected with the patents of the family of imidazole-containing peptidomimetics Carcinine (β-alanylhistamine), N-acetylcarnosine (N-acetyl-β-alanylhistidine) and Carnosine (β-alanyl-L-histidine) which are essential constituents possessing diverse biological and pharmacological chaperone properties in human tissues.

Skin beautification with oral non-hydrolized versions of carnosine and carcinine: Effective therapeutic management and cosmetic skincare solutions against oxidative glycation and free-radical production as a causal mechanism of diabetic complications and skin aging.

PubMed

Babizhayev, Mark A; Deyev, Anatoliy I; Savel'yeva, Ekaterina L; Lankin, Vadim Z; Yegorov, Yegor E

2012-10-01

Advanced glycation Maillard reaction end products (AGEs) are causing the complications of diabetes and skin aging, primarily via adventitious and cross-linking of proteins. Long-lived proteins such as structural collagen are particularly implicated as pathogenic targets of AGE processes. The formation of α-dicarbonyl compounds represents an important step for cross-linking proteins in the glycation or Maillard reaction. The purpose of this study was to investigate the contribution of glycation coupled to the glycation free-radical oxidation reactions as markers of protein damage in the aging of skin tissue proteins and diabetes. To elucidate the mechanism for the cross-linking reaction, we studied the reaction between a three-carbon α-dicarbonyl compound, methylglyoxal, and amino acids using EPR spectroscopy, a spectrophotometric kinetic assay of superoxide anion production at the site of glycation and a chemiluminescence technique. The transglycating activity, inhibition of transition metal ions peroxidative catalysts, resistance to hydrolysis of carnosine mimetic peptide-based compounds with carnosinase and the protective effects of carnosine, carcinine and related compounds against the oxidative damage of proteins and lipid membranes were assessed in a number of biochemical and model systems. A 4-month randomized, double-blind, controlled study was undertaken including 42 subjects where the oral supplement of non-hydrolized carnosine (Can-C Plus® formulation) was tested against placebo for 3 months followed by a 1-month supplement-free period for both groups to assess lasting effects. Assessment of the age-related skin parameters and oral treatment efficacy measurements included objective skin surface evaluation with Visioscan® VC 98 and visual assessment of skin appearance parameters. The results together confirm that a direct one-electron transfer between a Schiff base methylglyoxal dialkylimine (or its protonated form) and methylglyoxal is responsible for the generation of the cross-linked radical cation and the radical counteranion of methylglyoxal. Under aerobic conditions, molecular oxygen can then accept an electron from the methylglyoxal anion to generate the superoxide radical anion causing the propagation of oxidative stress chain reactions in the presence of transition metal ions. Carnosine stabilized from enzymatic hydrolysis, carcinine and leucyl-histidylhydrazide in patented formulations thereof, demonstrate the Schiff bases' transglycating activities concomitant with glycation site specific antioxidant activities and protection of proprietary antioxidant enzymes in the skin during aging and with diabetes lesions. During oral supplementation with stabilized from enzymatic hydrolysis carnosine (Can-C Plus® formulation), the skin parameters investigated showed a continuous and significant improvement in the active group during the 3 months of supplementation as compared to placebo. Visual investigation showed improvement of the overall skin appearance and a reduction of fine lines. No treatment-related side effects were reported. The finding that already-formed AGE cross-links can be pharmacologically severed and attendant pathology thereby reversed by non-hydrolized carnosine or carcinine in patented oral formulations thereof has broad implications for the skin beautification and therapeutics of the complications of diabetes and skin diseases associated with aging.

Laccase mediated-synthesis of hydroxycinnamoyl-peptide from ferulic acid and carnosine.

PubMed

Aljawish, Abdulhadi; Chevalot, Isabelle; Madad, Nidal; Paris, Cédric; Muniglia, Lionel

2016-06-10

Carnosine (CAR) dipeptide was functionalized with ferulic acid (FA) as substrate using laccase from Myceliophtora thermophila as biocatalyst. The enzymatic reaction was performed in aqueous medium under mild conditions (pH 7.5, 30°C) as an eco-friendly procedure. Results showed that this enzymatic process led to the synthesis of two new derivatives (P1, P2), from the coupling between CAR and FA derived products. Conditions allowing a high production of P1, P2 derivatives were determined with an optimal ratio of (FA: CAR) of (1:1.6) at optimal time reaction of 8h. Under these optimal conditions, the coupling between CAR and FA-products was demonstrated, resulting in the decrease of -NH2 groups (almost 50%) as quantified via derivatization. Due to the presence of FA in the structure of these new derivatives, they exhibited higher hydrophobic property than carnosine. Structural analyses by mass spectrometry showed that P1 and P2 (FA-CAR) derivatives exhibited the same molecular mass (MM 770g/mol) containing one CAR-molecule and three FA-molecules but with different chemical structures. Furthermore, these derivatives presented improved antioxidant (almost 10 times) and anti-proliferative (almost 18 times) properties in comparison with CAR. Moreover, P1 derivative exhibited higher antioxidant and anti-proliferative activities than P2 derivative, which confirmed the different structures of P1 and P2. These results suggested that the oxidized phenols coupling with carnosine is a promising process to enhance the CAR-properties. Copyright © 2016 Elsevier B.V. All rights reserved.

Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications

PubMed Central

Xie, Zhengzhi; Baba, Shahid P.; Sweeney, Brooke R.; Barski, Oleg A.

2015-01-01

Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. In most tissues, aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines, such as glutathione and histidine dipeptides. Histidine dipeptides are present in micromolar to millimolar range in the tissues of vertebrates, where they are involved in a variety of physiological functions such as pH buffering, metal chelation, oxidant and aldehyde scavenging. Histidine dipeptides such as carnosine form Michael adducts with lipid-derived unsaturated aldehydes, and react with carbohydrate-derived oxo- and hydroxy- aldehydes forming products of unknown structure. Although these peptides react with electrophilic molecules at lower rate than glutathione, they can protect glutathione from modification by oxidant and they may be important for aldehyde quenching in glutathione-depleted cells or extracellular space where glutathione is scarce. Consistent with in vitro findings, treatment with carnosine has been shown to diminish ischemic injury, improve glucose control, ameliorate the development of complications in animal models of diabetes and obesity, promote wound healing and decrease atherosclerosis. The protective effects of carnosine have been linked to its anti-oxidant properties, it ability to promote glycolysis, detoxify reactive aldehydes and enhance histamine levels. Thus, treatment with carnosine and related histidine dipeptides may be a promising strategy for the prevention and treatment of diseases associated with high carbonyl load. PMID:23313711

Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications.

PubMed

Xie, Zhengzhi; Baba, Shahid P; Sweeney, Brooke R; Barski, Oleg A

2013-02-25

Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. In most tissues, aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines, such as glutathione and histidine dipeptides. Histidine dipeptides are present in micromolar to millimolar range in the tissues of vertebrates, where they are involved in a variety of physiological functions such as pH buffering, metal chelation, oxidant and aldehyde scavenging. Histidine dipeptides such as carnosine form Michael adducts with lipid-derived unsaturated aldehydes, and react with carbohydrate-derived oxo- and hydroxy-aldehydes forming products of unknown structure. Although these peptides react with electrophilic molecules at lower rate than glutathione, they can protect glutathione from modification by oxidant and they may be important for aldehyde quenching in glutathione-depleted cells or extracellular space where glutathione is scarce. Consistent with in vitro findings, treatment with carnosine has been shown to diminish ischemic injury, improve glucose control, ameliorate the development of complications in animal models of diabetes and obesity, promote wound healing and decrease atherosclerosis. The protective effects of carnosine have been linked to its anti-oxidant properties, its ability to promote glycolysis, detoxify reactive aldehydes and enhance histamine levels. Thus, treatment with carnosine and related histidine dipeptides may be a promising strategy for the prevention and treatment of diseases associated with high carbonyl load. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Quality preservation of reduced sodium pork patties: effects of antioxidants on colour and lipid stability.

PubMed

Cheng, Jen-Hua; Wang, Shu-Tai; Ockerman, Herbert W

2013-09-01

The purpose of this study was to explore the effect of lipid oxidation and colour change of precooked pork patties with reduced sodium and added antioxidants. This study can fill the gap of antioxidant application between meat products with regular and low salt content. For precooked pork patties, addition of sodium tripolyphosphate and carnosine increased pH values and cooking yields. Patties with ascorbic acid had significantly higher a* values compared to the other samples. There was no significant difference of b* values among treatments. Precooked pork patties with sodium tripolyphosphate or carnosine had significantly higher L* values compared to other patties. The addition of antioxidants reduced lipid oxidation in precooked pork patties during refrigerated storage, except for the addition of 0.5% carnosine. Tripolyphosphate and ascorbic acid were successfully proven to be effective in retarding lipid oxidation and preserve the colour stability in reduced salt pork patties. This study provides a preliminary foundation of keeping meat products from lipid oxidation and maintaining in better stability. © 2013 Society of Chemical Industry.

Effects of natural antioxidants on colour stability, lipid oxidation and metmyoglobin reducing activity in raw beef patties.

PubMed

Liu, Fang; Xu, Qian; Dai, Ruitong; Ni, Yuanying

2015-01-01

Minced meats undergo oxidative changes and develop rancidity more quickly than intact muscle since grinding exposes more of the muscle surface to air and microbial contamination. Due to concerns about toxicological safety of synthetic antioxidants, recent studies have put more focus on natural antioxidant compounds derived from food components. The effects of four natural antioxidants (vitamin E, carnosine, grape seed extract and tea catechins) on oxidative processes and metmyoglobin reducing activity in raw beef patties during refrigerated (4°C) storage were investigated and the results were compared with butylated hydroxyanisole treatment patties. The correlation of lipid oxidation, colour and metmyoglobin reducing activity of beef patties were also studied. Samples treated with carnosine had the highest redness values on the eighth day. Tea catechins, vitamin E and grape seed extract showed higher protective effect against lipid oxidation than carnosine. Metmyoglobin reducing activity increased greatly in all samples during the storage. Significant correlation between redness value and lipid oxidation was demonstrated, while a weak correlation between metmyoglobin reducing activity and any other parameters was shown.

Carnosine ameliorates lens protein turbidity formations by inhibiting calpain proteolysis and ultraviolet C-induced degradation.

PubMed

Liao, Jiahn-Haur; Lin, I-Lin; Huang, Kai-Fa; Kuo, Pei-Ting; Wu, Shih-Hsiung; Wu, Tzu-Hua

2014-06-25

Carnosine (CAR) is an endogenous peptide and present in lens, but there is little evidence for its effectiveness in calpain-induced proteolysis inhibition and its differential effects toward different wavelengths of ultraviolet (UV) irradiation. This study aimed to develop three in vitro cataract models to compare the mechanisms underlying the protective activities of CAR. Crude crystallins extracted from porcine lenses were used for antiproteolysis assays, and purified γ-crystallins were used for anti-UV assays. The turbidity in those in vitro models mimics cataract formation and was assayed by measuring optical density (OD) at 405 nm. The effectiveness of CAR on calpain-induced proteolysis was studied at 37 and 58 °C. Patterns of proteins were then analyzed by SDS-PAGE. The turbidity was reduced significantly (p<0.05) at 60 min measurements with the increased concentration of CAR (10-300 mM). SDS-PAGE showed that the decreased intensities at both ∼28 and ∼30 kDa protein bands in heat-enhanced assays were ameliorated by CAR at ≥10 mM concentrations. In UV-B studies, CAR (200, 300 mM) reduced the turbidity of γ-crystallin significantly (p<0.05) at 6 h observations. The turbidity of samples containing γ-crystallins was ameliorated while incubated with CAR (100, 300 mM) significantly (p<0.05) following 4 h of exposure to UV-C. SDS-PAGE showed that the presence of CAR reduced UV-B-induced aggregation of γ-crystallins at ∼44 kDa and resulted in less loss of γ-crystallin following UV-C exposure. The result of modeling also suggests that CAR acts as an inhibitor of calpain. In conclusion, CAR protects lens proteins more readily by inhibiting proteolysis and UV-C-induced degradation than aggregation induced by UV-B irradiation.

[Using carnosine and natural antioxidants for the prophylaxis of acute post-loading oxidative stress].

PubMed

Rozhkova, E A; Ordzhonikidze, Z G; Druzhinin, A E; Seĭfulla, N R; Paniushkin, V V; Kuznetsov, Iu M

2007-01-01

The effects of a submaximum single physical load with a mixed aerobic-anaerobic character (combined rowing test) on the intensity of lipid peroxidation (LPO) processes, antioxidant state of the organism, and rheological properties of blood have been studied in a group of athletes. The administration of natural antioxidants significantly decreased the LPO stress induced by the physical load, reduced the suppression of the antioxidant system of the organism, and normalized the LPO-disturbed hemorheological parameters. Antioxidants such as carnosine, cytamine, and apilac can be used as non-doping means for the accelerated recovery and increase in the physical work capacity in athletes.

Neuroprotective effect of the carnosine - α-lipoic acid nanomicellar complex in a model of early-stage Parkinson's disease.

PubMed

Kulikova, Olga I; Berezhnoy, Daniil S; Stvolinsky, Sergey L; Lopachev, Alexander V; Orlova, Valentina S; Fedorova, Tatiana N

2018-06-01

In a model of early-stage Parkinson's disease induced by a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to Wistar rats, a neuroprotective effect of a new derivative of carnosine and α-lipoic acid (C/LA nanomicellar complex) was demonstrated. Acute intraperitoneal administration of carnosine, α-lipoic acid and C/LA complex following MPTP administration normalized the total antioxidant activity in the brain tissue. Of all the compounds tested only C/LA complex normalized the metabolism of dopamine (DA) and serotonin (5-HT), while its components did not show similar effects when used separately. C/LA complex effectively restored the level of DA metabolites: the level of DOPAC was increased by 24.7 ± 5.6% compared to the animals that had received MPTP only, and the level of HVA was restored to the values observed in the intact animals. Integral metabolic indices of DA (DOPAC/DA and HVA/DA ratios) and 5-HT turnover (5-HIAA/5-HT ratio) in the striatum tended to increase in case of C/LA complex administration. Copyright © 2018 Elsevier Inc. All rights reserved.

Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

PubMed Central

Riad, Sandra; Bougherara, Habiba

2015-01-01

Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

Do fatty acids help in overcoming reading difficulties? A double-blind, placebo-controlled study of the effects of eicosapentaenoic acid and carnosine supplementation on children with dyslexia.

PubMed

Kairaluoma, L; Närhi, V; Ahonen, T; Westerholm, J; Aro, M

2009-01-01

There are claims that dietary supplementation of unsaturated fatty acids could help children with dyslexia to overcome their reading problems. However, these claims have not yet been empirically tested. This study was designed to test whether dietary supplementation was superior to placebo in treating reading, spelling or other reading-related skills of children with dyslexia. The experimental group (eicosapentaenoic acid, EPA, n = 30) ate dietary supplements and the control group (placebo, n = 31) placebos during the 90-day treatment period. The supplements contained omega-3 fatty acid (ethyl-EPA, 500 mg/day) and carnosine (400 mg/day). The groups were matched for reading skills, grade, gender, attention problems, intelligence and amount of special education. The literacy-related skills of the two groups were assessed before and after the treatment period. No group differences were observed between EPA and placebo in measures of reading accuracy or speed, spelling, decoding fluency, arithmetical skills, reading-related language skills, attention or behavioural problems. The present findings do not support the hypothesis that omega-3 fatty acid (ethyl-EPA) or carnosine has a role in the treatment of reading and spelling problems in children with dyslexia.

Zinc L-carnosine suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 murine macrophages cell line via activation of Nrf2/HO-1 signaling pathway.

PubMed

Ooi, Theng Choon; Chan, Kok Meng; Sharif, Razinah

2017-10-01

Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer. In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages. We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay. Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine. Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.

Effects of 28 days of beta-alanine and creatine supplementation on muscle carnosine, body composition and exercise performance in recreationally active females.

PubMed

Kresta, Julie Y; Oliver, Jonathan M; Jagim, Andrew R; Fluckey, James; Riechman, Steven; Kelly, Katherine; Meininger, Cynthia; Mertens-Talcott, Susanne U; Rasmussen, Christopher; Kreider, Richard B

2014-01-01

The purpose of this study was to examine the short-term and chronic effects of β-ALA supplementation with and without creatine monohydrate on body composition, aerobic and anaerobic exercise performance, and muscle carnosine and creatine levels in college-aged recreationally active females. Thirty-two females were randomized in a double-blind, placebo-controlled manner into one of four supplementation groups: β-ALA only (BA, n = 8), creatine only (CRE, n = 8), β-ALA and creatine combined (BAC, n = 9) and placebo (PLA, n = 7). Participants supplemented for four weeks included a loading phase for the creatine for week 1 of 0.3 g/kg of body weight and a maintenance phase for weeks 2-4 of 0.1 g/kg of body weight, with or without a continuous dose of β-ALA of 0.1 g/kg of body weight with doses rounded to the nearest 800 mg capsule providing an average of 6.1 ± 0.7 g/day of β-ALA. Participants reported for testing at baseline, day 7 and day 28. Testing sessions consisted of obtaining a resting muscle biopsy of the vastus lateralis, body composition measurements, performing a graded exercise test on the cycle ergometer for VO2peak with lactate threshold determination, and multiple Wingate anaerobic capacity tests. Although mean changes were consistent with prior studies and large effect sizes were noted, no significant differences were observed among groups in changes in muscle carnosine levels (BA 35.3 ± 45; BAC 42.5 ± 99; CRE 0.72 ± 27; PLA 13.9 ± 44%, p = 0.59). Similarly, although changes in muscle phosphagen levels after one week of supplementation were consistent with prior reports and large effect sizes were seen, no statistically significant effects were observed among groups in changes in muscle phosphagen levels and the impact of CRE supplementation appeared to diminish during the maintenance phase. Additionally, significant time × group × Wingate interactions were observed among groups for repeated sprint peak power normalized to bodyweight (p = 0.02) and rate of fatigue (p = 0.04). Results of the present study did not reveal any consistent additive benefits of BA and CRE supplementation in recreationally active women.

Changes in endogenous bioactive compounds of Korean native chicken meat at different ages and during cooking.

PubMed

Jayasena, Dinesh D; Jung, Samooel; Bae, Young Sik; Kim, Sun Hyo; Lee, Soo Kee; Lee, Jun Heon; Jo, Cheorun

2014-07-01

This study aimed to examine the effect of bird age on the contents of endogenous bioactive compounds, including carnosine, anserine, creatine, betaine, and carnitine, in meat from a certified meat-type commercial Korean native chicken strain (KNC; Woorimatdag). Additionally, the effects of the meat type (breast or leg meat) and the state of the meat (raw or cooked) were examined. Cocks of KNC were raised under similar standard commercial conditions at a commercial chicken farm. At various ages (10, 11, 12, 13, and 14 wk), breast and leg meats from a total of 10 birds from each age group were obtained. Raw and cooked meat samples were then prepared separately and analyzed for bioactive compounds. The age of the KNC had a significant effect only on the betaine content. The breast meat of KNC had higher amounts of carnosine and anserine but had lower amounts of betaine and carnitine than the leg meat (P < 0.05). The KNC meat lost significant amounts of all bioactive compounds during cooking (P < 0.05). Leg meat had high retention percentages of carnosine and anserine after cooking, whereas breast meat showed almost complete retention of betaine and carnitine. The results of this study provide useful and rare information regarding the presence, amounts, and determinants of endogenous bioactive compounds in KNC meat, which can be useful for selection and breeding programs, and also for popularizing indigenous chicken meat. © 2014 Poultry Science Association Inc.

Antioxidation status and histidine dipeptides content in broiler blood and muscles depending on protein sources in feed.

PubMed

Kopeć, W; Jamroz, D; Wiliczkiewicz, A; Biazik, E; Hikawczuk, T; Skiba, T; Pudło, A; Orda, J

2013-06-01

One-day-old chickens were fed mixtures containing different raw materials (fish by-products meal, porcine blood cells meal, blood meal, wheat gluten, fodder yeast), as a source of histidine and β-alanine - components of carnosine. Control birds were administered a feed mixture, in which soy bean meal was the main protein source. The bodyweight, feed consumption and conversion, antioxidant characteristics and histidine dipeptides content in blood and muscles, and also amino acid composition of chicken meat on day 34 post-hatch were recorded. The best (p < 0.05) performance and feed conversion were observed in chickens fed mixture containing porcine blood cells meal. In blood plasma of control chickens, a significantly (p < 0.01) higher ability to scavenge DPPH radicals was found. However, the highest catalase activity in erythrocytes was determined in chickens fed mixtures with blood by-products. Insignificant differences in both carnosine and anserine levels in plasma between treatments were noted. Breast muscles from control birds were characterized by lower activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) (p < 0.05; p < 0.01), than those from chickens fed blood by-products. Improved ability to reduce ferric ions (FRAP) (p < 0.01) and carnosine content in meat from chickens fed blood cell meal were recorded. No direct relations between amino acids content in feed mixtures and in meat were observed. © 2012 Blackwell Verlag GmbH.

Non-hydrolyzed in digestive tract and blood natural L-carnosine peptide ("bioactivated Jewish penicillin") as a panacea of tomorrow for various flu ailments: signaling activity attenuating nitric oxide (NO) production, cytostasis, and NO-dependent inhibition of influenza virus replication in macrophages in the human body infected with the virulent swine influenza A (H1N1) virus.

PubMed

Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

2013-01-01

Influenza (flu) is caused by a highly contagious virus that is spread by coughs and sneezes. Flu symptoms include high fever, chills and sweating, sore throat, weakness, headache, muscle and joint pains, and cough. Older people and those with an underlying medical condition are more likely to develop serious complications, including secondary bacterial pneumonia, primary influenza pneumonia, and inflammation of the brain or heart. There are three types of flu virus: A, B, and C. The flu virus has a unique ability to change its surface structure. This allows it to escape recognition by the body's immune system and cause widespread illness (epidemics and pandemics). Most cases of influenza occur within a 6- to 8-week period during winter and spring. Epidemics occur when there are minor changes in the nature of the virus so that more people within a community are susceptible. Influenza A is more likely to cause epidemics. Pandemics (worldwide epidemics) occur when there are major changes in the virus so that the disease affects a large proportion of people in a geographic region or on more than one continent. The findings presented in this article have many important implications for understanding the influenza A (H1N1) viral pathogenesis, prevention, and treatment. Direct viral cytotoxicity (referred cytopathic effect) is only a fraction of several types of events induced by virus infection. Nitric oxide and oxygen free radicals such as superoxide anion (O2-·) are generated markedly in influenza A (including H1N1) virus-infected host boosts, and these molecular species are identified as the potent pathogenic agents. The mutual interaction of nitric oxide (NO) with O2-· resulting in the formation of peroxynitrite is operative in the pathogenic mechanism of influenza virus pneumonia. Influenza virus infection involves pathological events in which oxygen free radicals play an important role in the pathogenesis. The toxicity and reactivity of oxygen radicals generated in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. In this article, the types of protection of carnosine in its bioavailable non-hydrolyzed forms in formulations are considered against reactive oxygen radical species-dependent injury, peroxynitrite damage, and other types of viral injuries in which impaired immune responses to viral pathogens are usually involved. Carnosine (β-alanyl-L-histidine) shows the pharmacological intracellular correction of NO release, which might be one of the important factors of natural immunity in controlling the initial stages of influenza A virus infection (inhibition of virus replication) and virus-induced regulation of cytokine gene expression. The protective effects of orally applied non-hydrolyzed formulated species of carnosine include at least the direct interaction with NO, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of cytokines and chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in carnosine and its derivative anserine (β-alanyl-1-methyl-L-histidine), could contribute to the pathogenesis and prevention of influenza virus infections and cold but have a limitation due to the susceptibility to enzymatic hydrolysis of dipeptides with serum carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The formulations of non-hydrolyzed in digestive tract and blood natural carnosine peptide and isopeptide (γ-glutamyl-carnosine) products, manufactured at the cGMP-certified facility and patented by the authors, have promise in the control and prevention of influenza A (H1N1) virus infection, cough, and cold.

[Chaperon-like anticataract agents, the antiaggregants of lens crystallin. Communication 4. Study of the effect of a mixture of di- and tetrapeptides on a prolonged rat model of UV-induced cataract].

PubMed

Avetisov, S E; Polunin, G S; Sheremet, N L; Makarov, I A; Fedorov, A A; Karpova, O E; Muranov, K O; Dizhevskaia, A K; Soustov, L V; Chelnokov, E V; Bitiurin, N M; Sapogova, N V; Nemov, V V; Bodyrev, A A; Ostrovskiĭ, M A

2008-01-01

There is a potential of therapeutic action on certain stages of caractogenesis, in particular on the aggregation of water-soluble proteins of cytoplasmic lens fiber cells, giving rise to insoluble protein complexes. The effect of a combined preparation (N-acetyl carnosine and D-patethine), acting by the chaperon-like mechanism, was studied in vivo on a prolonged rat model of UV-induced cataract. The use of the combined preparation consisting of a mixture of peptides of N-acetyl carnosine and D-patethine in a ratio of 1:1 as ocular instillations and intraperitoneal injections could slow down the development of UV-induced cataract in vivo. Pathomorphological studies suggest that the combined preparation has a protective effect on lens tissue when the rat model of UV-induced cataract is employed.

Sensomics-Based Molecularization of the Taste of Pot-au-Feu, a Traditional Meat/Vegetable Broth.

PubMed

Kranz, Maximilian; Viton, Florian; Smarrito-Menozzi, Candice; Hofmann, Thomas

2018-01-10

Targeted quantification of 49 basic taste-active molecules, followed by the calculation of dose-over-threshold (DoT) factors, and taste re-engineering experiments revealed minerals, nucleotides/nucleosides, amino acids, organic acids, and carbohydrates as the key compounds of Pot-au-Feu, a traditional broth preparation from beef cuts and vegetables. Moreover, the dipeptide carnosine was identified to be the key inducer for the white-meaty and thick-sour orosensation of the broth, next to anserine and 1-deoxy-d-fructosyl-N-β-alanyl-l-histidine, the latter of which has been identified for the first time by means of a sensory-guided fractionation. Sensory studies revealed the threshold concentration of carnosine in model broth to decrease by a factor of 5 upon nonenzymatic glycosylation to reach 4.4 mmol/L for its Amadori product 1-deoxy-d-fructosyl-N-β-alanyl-l-histidine.

Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

PubMed

Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

2016-01-01

The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.

1 H NMRS of carnosine combined with 31 P NMRS to better characterize skeletal muscle pH dysregulation in Duchenne muscular dystrophy.

PubMed

Reyngoudt, Harmen; Turk, Suna; Carlier, Pierre G

2018-01-01

In recent years, quantitative nuclear magnetic resonance imaging and spectroscopy (NMRI and NMRS) have been used more systematically as outcome measures in natural history and clinical trial studies for Duchenne muscular dystrophy (DMD). Whereas most of these studies have emphasized the evaluation of the fat fraction as an assessment for disease severity, less focus has been placed on metabolic indices measured by NMRS. 31 P NMRS in DMD reveals an alkaline inorganic phosphate (P i ) pool, originating from either leaky dystrophic myocytes or an increased interstitial space. 1 H NMRS, exploiting the pH-sensitive proton resonances of carnosine, an intracellular dipeptide, was used to distinguish between these two hypotheses. NMR data were obtained in 23 patients with DMD and 14 healthy subjects on a 3-T clinical NMR system. Both 31 P and 1 H NMRS data were acquired at the level of the gastrocnemius medialis muscle. A multi-slice multi-echo imaging acquisition was performed for the determination of water T 2 and fat fraction in the same region of interest. Whereas nearly all patients with DMD showed an elevated pH compared with healthy controls when using 31 P NMRS, 1 H NMRS-determined pH was not systematically increased. As expected, the carnosine-based intracellular pH was never found to be alkaline in the absence of a concurrent P i -based pH elevation. In addition, abnormal intracellular pH, based on carnosine, was never associated with normal water T 2 values. We conclude that, in one group of patients, both 1 H and 31 P NMRS showed an alkaline pH, originating from the intracellular compartment and reflecting ionic dysregulation in dystrophic myocytes. In the other patients with DMD, intracellular pH was normal, but an alkaline P i pool was still present, suggesting an extracellular origin, probably revealing an expanded interstitial volume fraction, often associated with fibrotic changes. The data demonstrate that 1 H NMRS could serve as a biomarker to assess the normalization of intramyocytic pH and sarcolemmal permeability following therapy inducing dystrophin expression in patients with DMD. Copyright © 2017 John Wiley & Sons, Ltd.

Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats.

PubMed

Kumral, A; Giriş, M; Soluk-Tekkeşin, M; Olgaç, V; Doğru-Abbasoğlu, S; Türkoğlu, Ü; Uysal, M

2016-06-01

Oxidative stress plays an important role in doxorubicin (DOX)-induced toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of this study was to evaluate the decreasing or preventive effect of CAR alone or combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver, and brain of rats. Rats were treated with CAR (250 mg kg(-1) day(-1); intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg(-1) α-tocopherol; once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of treatment, rats were injected with a single dose of DOX (30 mg kg(-1), i.p.). Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and oxidative stress parameters in tissues were measured. We also determined thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC), and glutathione levels and antioxidant enzyme activities. DOX resulted in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to decreases in serum cTnI levels and ALT and AST activities. These treatments reduced prooxidant status and ameloriated histopathologic findings in the examined tissues. Our results may indicate that CAR alone, especially in combination with Vit E, protect against DOX-induced toxicity in heart, liver, and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and renal markers and restoration of the prooxidant state and amelioration of histopathologic changes. © The Author(s) 2015.

Oral Administration of Forskolin, Homotaurine, Carnosine, and Folic Acid in Patients with Primary Open Angle Glaucoma: Changes in Intraocular Pressure, Pattern Electroretinogram Amplitude, and Foveal Sensitivity.

PubMed

Mutolo, Maria Giulia; Albanese, Giuseppe; Rusciano, Dario; Pescosolido, Nicola

2016-04-01

To evaluate the effects of a food supplement containing forskolin, homotaurine, carnosine, folic acid, vitamins B1, B2, B6, and magnesium in patients with primary open angle glaucoma (POAG) already in treatment and compensated by intraocular pressure (IOP)-lowering drugs, during a period of 12 months. Twenty-two patients (44 eyes) with POAG, with their IOP compensated by topical drugs, were enrolled and randomly assigned to the food supplement or control treatment group. The additional food supplement treatment consisted of 2 tablets per day (1 in the morning, 1 in the evening) given for 1 year of a balanced association of homotaurine, Coleus forskohlii root extract, L-carnosine, folic acid, vitamins B1, B2, B6, and magnesium. Pattern Electroretinogram (PERG) amplitude, foveal sensitivity obtained with the visual field analyzer frequency doubling technology, and IOP were detected at enrollment (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). We observed in treated patients a significant further decrease of IOP and an improvement of PERG amplitude at 6, 9, and 12 months, and foveal sensitivity at 12 months. All values remained substantially stable in control patients. The results of the present pilot study indicate that the components of the food supplement reach the eye in a detectable manner, as evidenced by the effects on the IOP. Moreover, they suggest a short-term neuroactive effect, as indicated by the improvement of PERG amplitude and foveal sensitivity in treated, but not in control patients.

The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, C.H.; Luk, C.T.; Ogle, C.W.

1991-01-01

Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint stress induced severe hemorrhagic lesions together with increased mast cell degranulation and {beta}-glucuronidase release in the gastric glandular mucosa. A-103 pretreatment with a single oral dose reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10{sup {minus}7}, 10{sup {minus}6}, 10{sup {minus}5} or 10{sup {minus}4} M, with isolated hepatic lysosomes, it significantly reduced themore » spontaneous release of {beta}-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z-103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa.« less

High resolution magic angle spinning NMR spectroscopy reveals that pectoralis muscle dystrophy in chicken is associated with reduced muscle content of anserine and carnosine.

PubMed

Sundekilde, Ulrik K; Rasmussen, Martin K; Young, Jette F; Bertram, Hanne Christine

2017-02-15

Increased incidences of pectoralis muscle dystrophy are observed in commercial chicken products, but the muscle physiological causes for the condition remain to be identified. In the present study a high-resolution magic angle spinning (HR-MAS) proton ((1)H) NMR spectroscopic examination of intact pectoralis muscle samples (n=77) were conducted to explore metabolite perturbations associated with the muscle dystrophy condition for the very first time. Both in chicken with an age of 21 and 31days, respectively, pectoralis muscle dystrophy was associated with a significantly lower content of anserine (p=0.034), carnosine (p=0.019) and creatine (p=0.049). These findings must be considered intriguing as they corroborate that characteristic muscle di-peptides composed of β-alanine and histidine derivatives such as anserine are extremely important in homeostasis of contractile muscles as a results of their role as buffering, anti-oxidative, and anti-glycation capacities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioactivation antioxidant and transglycating properties of N-acetylcarnosine autoinduction prodrug of a dipeptide L-carnosine in mucoadhesive drug delivery eye-drop formulation: powerful eye health application technique and therapeutic platform.

PubMed

Babizhayev, Mark A

2012-06-01

A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of the study document that the therapeutic benefit in clinical trials is associated with the bioactivation universal antioxidant and transglycating properties of N-acetylcarnosine acting as the ophthalmic prodrug of L-carnosine, and depends on the nature of the specific drug delivery lubricant eye-drop formulation applied as the topical solution. The research highlights findings in N-acetylcarnosine prodrug activation, transport mechanisms, drug-to-drug interactions, and formulations in order to unlock the optimization of complicated ocular pharmacology of N-acetylcarnosine. Patented N-acetylcarnosine lubricant eye-drop formula was marketed as numerous human biological brands reaching important distribution networks on over 550 000 bottles sold. Nature Does Nothing Uselessly. -Aristotle Copyright © 2011 John Wiley & Sons, Ltd.

Telomere Attrition in Human Lens Epithelial Cells Associated with Oxidative Stress Provide a New Therapeutic Target for the Treatment, Dissolving and Prevention of Cataract with N-Acetylcarnosine Lubricant Eye Drops. Kinetic, Pharmacological and Activity-Dependent Separation of Therapeutic Targeting: Transcorneal Penetration and Delivery of L-Carnosine in the Aqueous Humor and Hormone-Like Hypothalamic Antiaging Effects of the Instilled Ophthalmic Drug Through a Safe Eye Medication Technique.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2016-01-01

Visual impairment broadly impacts the ability of affected people to maintain their function and to remain independent during their daily occupations as they grow older. Visual impairment affects survival of older patients, quality of life, can affect a person's self-ranking of health, may be associated with social and functional decline, use of community support services, depression, falls, nursing home placement, and increased mortality. It has been hypothesized that senile cataract may serve as a marker for generalised tissue aging, since structural changes occurring in the proteins of the lens during cataract formation are similar to those which occur elsewhere as part of the aging process. The published analysis revealed a strong age-dependent relationship between undergoing cataract surgery and subsequent mortality. Nuclear opacity, particularly severe nuclear opacity, and mixed opacities with nuclear were significant predictors of mortality independent of body mass index, comorbid conditions, smoking, age, race, and sex. The lens opacity status is considered as an independent predictor of 2-year mortality, an association that could not be explained by potential confounders. Telomeres have become important biomarkers for aging as well as for oxidative stress-related disease. The lens epithelium is especially vulnerable to oxidative stress. Oxidative damage to the cuboidal epithelial cells on the anterior surface of the lens mediated by reactive oxygen species and phospholipid hydroperoxides can precede and contribute to human lens cataract formation. The erosion and shortening of telomeres in human lens epithelial cells in the lack of telomerase activity has been recognized as a primary cause of premature lens senescence phenotype that trigger human cataractogenesis. In this study we aimed to be focused on research defining the mechanisms that underlie linkages among telomere attrition in human lens epithelial cells associated with oxidative stress, biology of the lens response to oxidative damages, aging and health, cataract versus neuroendocrine regulation and disease. The cumulative results demonstrate that carnosine, released ophthalmically from the patented 1% Nacetylcarnosine prodrug lubricant eye drops, at physiological concentration might remarkably reduce the rate of telomere shortening in the lens cells subjected to oxidative stress in the lack of efficient antioxidant lens protection. Carnosine promotes the protection of normal cells from acquiring phenotypic characteristics of cellular senescence. The data of visual functions (visual acuity, glare sensitivity) in older adult subjects and older subjects with cataract treated with 1% N-acetylcarnosine lubricant eye drops showed significant improvement as compared, by contrast with the control group which showed generally no improvement in visual functions, with no difference from baseline in visual acuity and glare sensitivity readings. N-acetylcarnosine derived from the lubricant eye drops may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and gradually hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging and anti-cataract physiological function. The research utilizing the N-acetylcarnosine lubricant eye drops powerful therapeutic platform provides the findings related to the intraocular uptake exposure sources as well as a timing dosage and duration systemic absorption of said preparation from the conjunctional sac reaching the hypothalamus with activities transfer into the hypothalamic-neuroendocrine pathways affecting across the hypothalamus metabolic pathway the telomere biology and cataract disease occurrence, reversal and prevention and the average expected lifespan of an individual. Such findings can be translated into clinical practice and may provide a basis for personalized cataract disease and aging prevention and treatment approaches.

Carnosine supplementation to an all-plant protein diet for rainbow trout (Oncorhynchus mykiss).

USDA-ARS?s Scientific Manuscript database

Fishmeal may contain “unknown growth factors” that have yet to be identified for their physiological role. As fishmeal levels in rainbow trout (Oncorhynchus mykiss) feeds are reduced, the dietary loss of these compounds may contribute to growth reductions. One such compound, identified in fishmeal...

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Zhenhua

Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanolmore » by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.« less

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

PubMed

Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

2016-10-01

Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. Copyright © 2016 Elsevier Inc. All rights reserved.

[Cycloferon biological activity characteristics].

PubMed

Utkina, T M; Potekhina, L P; Kartashova, O L; Vasilchenko, A S

2014-01-01

Study the effect of cycloferon in experimental and clinical conditions on persistence properties of aurococci as well as features of their morpho-functional reaction by atomic force microscopy. The study was carried out in 12 Staphylococcus aureus clones isolated from mucous membrane of nose anterior part of a resident carrier. The effect of cycloferon in vivo was evaluated in 26 resident staphylococci carriers under the control of anti-carnosine activity of staphylococci. Anti-carnosine activity was determined by O.V. Bukharin et al. (1999), biofilm formation -by G.A. O'Toole et al. (2000). Staphylococci treated with cycloferon were studied by atomic force microscopy in contact mode using scanning probe SMM-2000 microscope. The decrease of persistence properties of staphylococci under the effect of cycloferon in vitro and in vivo may be examined as one of the mechanisms of biological activity of the preparation. A significant increase of S. aureus surface roughness and changes in their morphology under the effect of cycloferon allow stating the disorder of barrier functions in the aurococci cell wall. The data obtained expand the understanding of cycloferon biological activity mechanisms.

Nutrients Composition in Fit Snacks Made from Ostrich, Beef and Chicken Dried Meat.

PubMed

Zdanowska-Sąsiadek, Żaneta; Marchewka, Joanna; Horbańczuk, Jarosław Olav; Wierzbicka, Agnieszka; Lipińska, Paulina; Jóźwik, Artur; Atanasov, Atanas G; Huminiecki, Łukasz; Sieroń, Aleksander; Sieroń, Karolina; Strzałkowska, Nina; Stelmasiak, Adrian; De Smet, Stefaan; Van Hecke, Thomas; Hoffman, Louwrens C

2018-05-25

The aim of the study was to compare three types of meat snacks made from ostrich, beef, and chicken meat in relation to their nutrients content including fat, fatty acids, heme iron, and peptides, like anserine and carnosine, from which human health may potentially benefit. Dry meat samples were produced, from one type of muscle, obtained from ostrich ( m. ambiens ), beef ( m. semimembranosus ), and broiler chicken meat ( m. pectoralis major ). The composition of dried ostrich, beef, and chicken meat, with and without spices was compared. We show that meat snacks made from ostrich, beef, and chicken meat were characterized by high concentration of nutrients including proteins, minerals (heme iron especially in ostrich, than in beef), biologically active peptides (carnosine-in beef, anserine-in ostrich then in chicken meat). The, beneficial to human health, n -3 fatty acids levels differed significantly between species. Moreover, ostrich jerky contained four times less fat as compared to beef and half of that in chicken. In conclusion we can say that dried ostrich, beef, and chicken meat could be a good source of nutritional components.

A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial

PubMed Central

Liu, Yuejun; Cotillard, Aurélie; Vatier, Camille; Bastard, Jean-Philippe; Fellahi, Soraya; Stévant, Marie; Allatif, Omran; Langlois, Clotilde; Bieuvelet, Séverine; Brochot, Amandine; Guilbot, Angèle; Clément, Karine; Rizkalla, Salwa W.

2015-01-01

Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. Methods In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Results Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Conclusions Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. Trial Registration ClinicalTrials.gov NCT01530685 PMID:26406981

A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial.

PubMed

Liu, Yuejun; Cotillard, Aurélie; Vatier, Camille; Bastard, Jean-Philippe; Fellahi, Soraya; Stévant, Marie; Allatif, Omran; Langlois, Clotilde; Bieuvelet, Séverine; Brochot, Amandine; Guilbot, Angèle; Clément, Karine; Rizkalla, Salwa W

2015-01-01

Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥ 25 kg/m(2), unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24 ± 0.50 vs +0.12 ± 0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. ClinicalTrials.gov NCT01530685.

Chronic vs. Short-Term Acute O 3 Exposure Effects on Nocturnal Transpiration in Two Californian Oaks

Treesearch

Nancy Grulke; E. Paoletti; R. L. Heath

2007-01-01

We tested the effect of daytime chronic moderate ozone (O3) exposure, short-term acute exposure, and both chronic and acute O3 exposure combined on nocturnal transpiration in California black oak and blue oak seedlings. Chronic O3 exposure (70 ppb for 8 h/day) was implemented in open-top chambers for...

Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: Effect of sex and arsenic exposure

PubMed Central

Huang, Madelyn C.; Douillet, Christelle; Su, Mingming; Zhou, Kejun; Wu, Tao; Chen, Wenlian; Galanko, Joseph A.; Drobná, Zuzana; Saunders, R. Jesse; Martin, Elizabeth; Fry, Rebecca C.; Jia, Wei; Stýblo, Miroslav

2016-01-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID:26883664

Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

PubMed

Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

2011-08-01

Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults. Adolescents drank significantly more ethanol than adults on a gram per kilogram basis, with intake uninfluenced by prior ethanol exposure at both ages. Adolescents and adults may differ in their ability and/or propensity to adapt to chronic ethanol exposure, with adults, but not adolescents, developing chronic metabolic tolerance. However, this chronic exposure regimen was sufficient to disrupt baseline levels of social behavior at both ages. Taken together, these results suggest that, despite the age-related differences in tolerance development, adolescents are as susceptible as adults to consequences of chronic ethanol exposure, particularly in terms of disruptions in social behavior. Whether these effects would last into adulthood remains to be determined. Copyright © 2011 by the Research Society on Alcoholism.

The effect of amino acids and dipeptides on sodium-ion transport in rat enterocytes.

PubMed

Cheeseman, C I; Devlin, D

1985-02-14

Sodium efflux from isolated intestinal epithelial cells was measured during incubation with several different free amino acids and dipeptides. L-Leucine, which is cotransported with sodium across the brush border membrane, significantly stimulated the total sodium efflux and almost all of this increase involved the ouabain-sensitive flux, i.e., the active component. In contrast, glycyl-L-leucine had little or no effect on active sodium efflux either in the presence or absence of 0.1 mM bestatin, a peptide hydrolase inhibitor. A second dipeptide L-carnosine (beta-alanyl-L-histidine) which is poorly hydrolysed by enterocytes also had no effect upon sodium efflux. However, glycylglycine, which has been shown to be cotransported with sodium, did stimulate the ionic efflux. In addition, measurement of sodium uptake by sheets of small intestine showed that glycyl-L-leucine, carnosine and glycyl-L-proline failed to increase the uptake of the ion, while glycylglycine did significantly stimulate sodium uptake. These data indicate that some dipeptides are not cotransported with sodium, while others are. This suggests that there may well be multiple peptide transporters with very different characteristics in the brush border membrane of enterocytes.

Self-Assemblies of novel molecules, VECAR

NASA Astrophysics Data System (ADS)

Shrestha, Bijay; Kim, Hye-Young; Lee, Soojin; Novak, Brian; Moldovan, Dorel

2015-03-01

VECAR is a newly synthesized molecule, which is an amphiphilic antioxidant molecule that consists of two molecular groups, vitamin-E and Carnosine, linked by a hydrocarbon chain. The hydrocarbon chain is hydrophobic and both vitamin-E and Carnosine ends are hydrophilic. In the synthesis process, the length of the hydrophobic chain of VECAR molecules can vary from the shortest (n =0) to the longest (n =18), where n indicates the number of carbon atoms in the chain. We conducted MD simulation studies of self-assembly of VECAR molecules in water using GROMACS on LONI HPC resources. Our study shows that there is a strong correlation between the shape and atomistic structure of the self-assembled nano-structures (SANs) and the chain-length (n) of VECAR molecules. We will report the results of data analyses including the atomistic structure of each SANs and the dynamic and energetic mechanisms of their formation as function of time. In summary, both VECAR molecules of chain-length n =18 and 9 form worm-like micelles, which may be used as a drug delivery system. This research is supported by the Louisiana Board of Regents-RCS Grant (LEQSF(2012-15)-RD-A-19).

Endogenous functional compounds in Korean native chicken meat are dependent on sex, thermal processing and meat cut.

PubMed

Jayasena, Dinesh D; Jung, Samooel; Kim, Sun Hyo; Kim, Hyun Joo; Alahakoon, Amali U; Lee, Jun Heon; Jo, Cheorun

2015-03-15

In this study the effects of sex, meat cut and thermal processing on the carnosine, anserine, creatine, betaine and carnitine contents of Korean native chicken (KNC) meat were determined. Forty 1-day-old chicks (20 chicks of each sex) from a commercial KNC strain (Woorimatdag™) were reared under similar standard commercial conditions with similar diets, and ten birds of each sex were randomly selected and slaughtered at 14 weeks of age. Raw and cooked meat samples were prepared from both breast and leg meats and analyzed for the aforementioned functional compounds. Female KNCs had significantly higher betaine and creatine contents. The breast meat showed significantly higher carnosine and anserine contents, whereas the leg meat had a higher betaine and carnitine content. The content of all functional compounds was significantly depleted by thermal processing. This study confirms that KNC meat is a good source of the above-mentioned functional compounds, which can be considered attractive nutritional quality factors. However, their concentrations were significantly affected by thermal processing conditions, meat cut and sex. Further experiments are needed to select the best thermal processing method to preserve these functional compounds. © 2014 Society of Chemical Industry.

Analysis of human muscle extracts by proton NMR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venkatasubramanian, P.N.; Barany, M.; Arus, C.

1986-03-01

Perchloric acid extracts were prepared from pooled human muscle biopsies from patients diagnosed with scoliosis (SCOL) and cerebral palsy (CP). After neutralization with KOH and removal of perchlorate, the extracts were concentrated by freeze drying and dissolved in /sup 2/H/sub 2/O to contain 120 O.D. units at 280 nm per 0.5 ml. /sup 1/H NMR spectroscopy was performed with the 5 mm probe of a Varian XL300 instrument. Creatine, lactate, carnosine, and choline were the major resonances in the one-dimensional spectra of both extracts. With creatine as reference, 2.5-fold more lactate was found in SCOL than in CP, and amore » much smaller difference was also found in their carnosine content. Two-dimensional COSY comparison revealed several differences between the two extracts. Taurine, N-acetyl glutamate, glycerophosphoryl choline (or phosphoryl choline) and an unidentified spot were present only in the extract from SCOL but not in that from CP. On the other hand, aspartate, hydroxy-proline, carnitine and glycerophosphoryl ethanolamine were only present in CP but absent in SCOL. Alanine, cysteine, lysine and arginine appeared in both extracts without an apparent intensity difference.« less

Separation and detection of amino acid metabolites of Escherichia coli in microbial fuel cell with CE.

PubMed

Wang, Wei; Ma, Lihong; Lin, Ping; Xu, Kaixuan

2016-07-01

In this work, CE-LIF was employed to investigate the amino acid metabolites produced by Escherichia coli (E. coli) in microbial fuel cell (MFC). Two peptides, l-carnosine and l-alanyl-glycine, together with six amino acids, cystine, alanine, lysine, methionine, tyrosine, arginine were separated and detected in advance by a CE-LIF system coupled with a homemade spontaneous injection device. The injection device was devised to alleviate the effect of electrical discrimination for analytes during sample injection. All analytes could be completely separated within 8 min with detection limits of 20-300 nmol/L. Then this method was applied to analyze the substrate solution containing amino acid metabolites produced by E. coli. l-carnosine, l-alanyl-glycine, and cystine were used as the carbon, nitrogen, and sulfur source for the E. coli culture in the MFC to investigate the amino acid metabolites during metabolism. Two MFCs were used to compare the activity of metabolism of the bacteria. In the sample collected at the running time 200 h of MFC, the amino acid methionine was discovered as the metabolite with the concentrations 23.3 μg/L. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potentiation of intraocular absorption and drug metabolism of N-acetylcarnosine lubricant eye drops: drug interaction with sight threatening lipid peroxides in the treatment for age-related eye diseases.

PubMed

Babizhayev, Mark A

2009-01-01

Cataract is the dominant cause of blindness worldwide. Studies of the morphological structure and biophysical changes of the lens in human senile cataracts have demonstrated the disappearance of normal fiber structure in the opaque region of the lens and the disintegration of the lens fiber plasma membrane in the lens tissue. Morphological and biochemical techniques have revealed the regions in human cataractous lenses in which the plasma membrane derangement occurs as the primary light scattering centers which cause the observed lens opacity. Human cataract formation is mostly considered to be a multifactorial disease; however, oxidative stress might be one of the leading causes for both nuclear and cortical cataract. Phospholipid molecules modified with oxygen, accumulating in the lipid bilayer, change its geometry and impair lipid-lipid and protein-lipid interactions in lenticular fiber membranes. Electron microscopy data of human lenses at various stages of age-related cataract document that these disruptions were globules, vacuoles, multilamellar membranes, and clusters of highly undulating membranes. The opaque shades of cortical cataracts represent cohorts of locally affected fibres segregated from unaffected neighbouring fibres by plasma membranes. Other potential scattering centers found throughout the mature cataract nucleus included variations in staining density between adjacent cells, enlarged extracellular spaces between undulating membrane pairs, and protein-like deposits in the extracellular space. These affected parts had membranes with a fine globular aspect and in cross-section proved to be filled with medium to large globular elements. Lipid peroxidation (LPO) is a pathogenetic and causative factor of cataract. Increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides, fatty acid oxy-derivatives) and end fluorescent LPO products were detected in the lipid moieties of the aqueous humor samples and human lenses obtained from patients with senile and complicated cataracts as compared to normal donors. Utilizing the pharmacokinetic studies and the specific purity N-acetylcarnosine (NAC) ingredient as a source of pharmacological principal L-carnosine, we have created an ophthalmic time-release prodrug form combined with a muco-adhesive lubricant compound carboxymethylcellulose and other essential corneal absorption promoter excipients tailoring the increased intraocular absorption of L-carnosine in the aqueous humor and optimizing its specific effect in producing the basic antioxidant activity in vivo and reducing toxic effects of lipid peroxides to the crystalline lens. L-Carnosine that finds its way into the aqueous humor can accumulate in the lens tissue for a reasonable period of time. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation, subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. The NAC prodrug eye drops optimize the clinical effects for the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a particular NAC ophthalmic prodrug's clinical effect; the suitable magnitude and duration of this effect suggest dose-related bioavailability of L-camosine released from NAC in the aqueous humor of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders which have a component of oxidative stress in their genesis (including cataract and after-cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). The clinical efficacy of N-acetylcarnosine lubricant eye drops in ripe cataracts and retinal disorders can be enhanced in combined treatment with a patented oral formulation (Can-C Plus) of non-hydrolyzed carnosine including synergistic compounds (histidine, D-panthethine) with chaperone activity towards lens crystallins and oral supplementation with N-acetylcysteine providing an alternate means of boosting reduced glutathione (GSH) synthesis in the lens.

β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis.

PubMed

Saunders, Bryan; Elliott-Sale, Kirsty; Artioli, Guilherme G; Swinton, Paul A; Dolan, Eimear; Roschel, Hamilton; Sale, Craig; Gualano, Bruno

2017-04-01

To conduct a systematic review and meta-analysis of the evidence on the effects of β-alanine supplementation on exercise capacity and performance. This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data. 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms ('β-alanine' and 'Beta-alanine' combined with 'supplementation', 'exercise', 'training', 'athlete', 'performance' and 'carnosine'). Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses. 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI -0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of β-alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)). β-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors. These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with β-alanine supplementation based on their chosen exercise modality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Identification of a threshold for biomass exposure index for chronic bronchitis in rural women of Mysore district, Karnataka, India.

PubMed

Mahesh, P A; Jayaraj, B S; Prabhakar, A K; Chaya, S K; Vijaysimha, R

2013-01-01

Exposure to air pollution due to combustion of biomass fuels remains one of the significant risk factors for chronic respiratory diseases such as chronic bronchitis. There is a need to identify the minimum threshold level of biomass index that is significantly associated with chronic bronchitis. This study was undertaken to identify a threshold for biomass exposure index in a rural women population in Mysore district, south India. A cross-sectional survey was conducted in a representative population of Mysore and Nanjangud taluks. Eight villages each from Mysore and Nanjangud were randomly selected based on the list of villages from census 2001. A house-to-house survey was carried out by trained field workers using the Burden of Obstructive Diseases questionnaire, which evaluated the biomass smoke exposure and chronic bronchitis. All the women aged above 30 yr were included in the study. A total of 2011 women from Mysore and 1942 women from Nanjangud participated in the study. All women were non-smoking and used biomass fuels as the primary fuel for cooking. A threshold of biomass fuel exposure of 60 was identified on multivariate analysis in Mysore district after adjusting for age, passive smoking and working in a occupational exposure to dust, as the minimum required for a significant association with chronic bronchitis. One in every 20 women in Mysore district exposed to biomass fuel exposure index of 110 or more developed chronic bronchitis. The minimum threshold of biomass exposure index of 60 is necessary to have a significant risk of developing chronic bronchitis in women. The number needed to harm to develop chronic bronchitis reduces with increasing biomass exposure index and women residing in rural Nanjangud have a higher risk for developing chronic bronchitis as compared to women in Mysore.

Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: Effects on striatal dopamine and opioid systems in C57BL/6J mice

PubMed Central

Zhang, Yong; Schlussman, Stefan D.; Rabkin, Jacqui; Butelman, Eduardo R.; Ho, Ann; Kreek, Mary Jeanne

2013-01-01

Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an “addiction-like cycle” in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal /13-day saline + 1-day cocaine), chronic cocaine exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day withdrawal /14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection x 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered, modeling initial exposure. In “re-exposure” groups, after a 14-day injection-free period (modeling abstinence/withdrawal), mice that had received cocaine were re-injected with 14-day escalating-dose binge cocaine, whereas controls received saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to determine striatal dopamine content. Messenger RNA levels of preprodynorphin (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day escalating exposure or re-exposure than in those in the acute cocaine group and controls. Pdyn mRNA levels were higher in the cocaine groups than in controls. Long-term adaptation was observed across the stages of this addiction-like cycle, in that the effects of cocaine on dopamine levels were increased after re-exposure compared to exposure. Changes in striatal dopaminergic responses across chronic escalating cocaine exposure and re-exposure are a central feature of the neurobiology of relapsing addictive states. PMID:23164614

Occupational exposure and risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

PubMed

Alif, Sheikh M; Dharmage, Shyamali C; Bowatte, Gayan; Karahalios, Amalia; Benke, Geza; Dennekamp, Martine; Mehta, Amar J; Miedinger, David; Künzli, Nino; Probst-Hensch, Nicole; Matheson, Melanie C

2016-08-01

Due to contradictory literature we have performed a systematic review and meta-analyse of population-based studies that have used Job Exposure Matrices to assess occupational exposure and risk of Chronic Obstructive Pulmonary Disease (COPD). Two researchers independently searched databases for published articles using predefined inclusion criteria. Study quality was assessed, and results pooled for COPD and chronic bronchitis for exposure to biological dust, mineral dust, and gases/fumes using a fixed and random effect model. Five studies met predetermined inclusion criteria. The meta-analysis showed low exposure to mineral dust, and high exposure to gases/fumes were associated with an increased risk of COPD. We also found significantly increased the risk of chronic bronchitis for low and high exposure to biological dust and mineral dust. Expert commentary: The relationship between occupational exposure assessed by the JEM and the risk of COPD and chronic bronchitis shows significant association with occupational exposure. However, the heterogeneity of the meta-analyses suggests more wide population-based studies with older age groups and longitudinal phenotype assessment of COPD to clarify the role of occupational exposure to COPD risk.

Separation and determination of peptide metabolite of Bacillus licheniformis in a microbial fuel cell by high-speed capillary micellar electrokinetic chromatography.

PubMed

Wang, Wei; Bai, Ruiguang; Cai, Xiaoyu; Lin, Ping; Ma, Lihong

2017-11-01

A method using high-speed capillary micellar electrokinetic chromatography and a microbial fuel cell was applied to determine the metabolite of the peptides released by Bacillus licheniformis. Two peptides, l-carnosine and l-alanyl-l-glutamine were used as the substrate to feed Bacillus licheniformis in a microbial fuel cell. The metabolism process of the bacterium was monitored by analyzing the voltage outputs of the microbial fuel cell. A home-made spontaneous injection device was applied to perform high-speed capillary micellar electrokinetic chromatography. Under the optimized conditions, tryptophan, glycine, valine, tyrosine and the two peptides could be rapidly separated within 2.5 min with micellar electrokinetic chromatography mode. Then the method was applied to analyze the solutions sampled from the microbial fuel cell. After 92 h running, valine, as the metabolite, was successfully detected with concentration 3.90 × 10 -5 M. The results demonstrated that Bacillus licheniformis could convert l-carnosine and l-alanyl-l-glutamine into valine. The method employed in this work was proved to have great potential in analysis of metabolites, such as amino acids, for microorganisms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity.

PubMed

Shimura, Hideki; Tanaka, Ryota; Shimada, Yoshiaki; Yamashiro, Kazuo; Hattori, Nobutaka; Urabe, Takao

2017-11-22

Peptides with cytoprotective functions, including antioxidants and anti-infectives, could be useful therapeutics. Carnosine, β-alanine-histidine, is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His-His, or Tyr-His-Tyr are also of interest in this respect. We synthesized several histidine-containing peptides including glycine or alanine, and tested their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His, Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly-Gly-His), GAH was found to have the strongest cytoprotective activity. GAH decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes, and nuclear membrane permeability changes against hydrogen peroxide toxicity in PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells against damage caused by actinomycin D and staurosporine. Additionally, it was found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by hydrogen peroxide, as assessed by LDH leakage. Thus, a novel tripeptide, GAH, has been identified as having broad cytoprotective effects against hydrogen peroxide-induced cell damage.

Chronic Exposure to Zinc Chromate Induces Centrosome Amplification and Spindle Assembly Checkpoint Bypass in Human Lung Fibroblasts

PubMed Central

Holmes, Amie L.; Wise, Sandra S.; Pelsue, Stephen C.; Aboueissa, AbouEl-Makarim; Lingle, Wilma; Salisbury, Jeffery; Gallagher, Jamie; Wise, John Pierce

2010-01-01

Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen, however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no increase in aneuploidy after a 24 hour exposure to zinc chromate, but with more chronic exposures, zinc chromate induced concentration- and time-dependent increases in aneuploidy in the form of hypodiploidy, hyperdiploidy and tetraploidy. Zinc chromate also induced centrosome amplification in a concentration- and time-dependent manner in both interphase and mitotic cells after chronic exposure, producing cells with centriolar defects. Further, chronic exposure to zinc chromate induced concentration- and time-dependent increases in spindle assembly checkpoint bypass with increases in centromere spreading, premature centromere division and premature anaphase. Lastly, we found that chronic exposure to zinc chromate induced a G2 arrest. All together, these data indicate that zinc chromate can induce chromosome instability after prolonged exposures. PMID:20030412

Effects of chronic normobaric hypoxic and hypercapnic exposure in rats: Prevention of experimental chronic mountain sickness by hypercapnia

NASA Astrophysics Data System (ADS)

Lincoln, B.; Bonkovsky, H. L.; Ou, Lo-Chang

1987-09-01

A syndrome of experimental chronic mountain sickness can be produced in the Hilltop strain of Sprague-Dawley rats by chronic hypobaric hypoxic exposure. This syndrome is characterized by polycythemia, plasma hemoglobinemia, pulmonary hypertension and right ventricular hypertrophy with eventual failure and death. It has generally been assumed that these changes are caused by chronic hypoxemia, not by hypobaric exposure per se. We have now confirmed this directly by showing that chronic normobaric hypoxic exposure (10.5% O2) produces similar hematologic and hemodynamic changes. Further, the addition of hypercapnic exposure to the hypoxic exposure blunted or prevented the effects of the hypoxic exposure probably by stimulating respiration, thus increasing the rate of oxygen delivery to the cells. Changes in the rate-controlling enzymes of hepatic heme metabolism, 5-aminolevulinate synthase and heme oxygenase, and in cytochrome(s) P-450, the major hepatic hemoprotein(s), were also measured in hypoxic and hypercapnic rats. Hypoxia decreased 5-aminolevulinate synthase and increased cytochrome(s) P-450, probably by increasing the size of a “regulatory” heme pool within hepatocytes. These changes were also prevented by the addition of hypercapnic to hypoxic exposure.

Occupational exposures and chronic respiratory symptoms: a population-based study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korn, R.J.; Dockery, D.W.; Speizer, F.E.

1987-01-01

Data from a random sample of 8515 white adults residing in six cities in the eastern and midwestern United States were used to examine the relationships between occupational exposures to dust or to gases and fumes and chronic respiratory symptoms. 31% of the population had a history of occupational dust exposure and 30% reported exposure to gas or to fumes. After adjusting for smoking habits, age, gender, and city of residence, subjects with either occupational exposure had significantly elevated prevalence of chronic cough, chronic phlegm, persistent wheeze, and breathlessness. The adjusted relative odds of chronic respiratory symptoms for subjects exposedmore » to dust ranged from 1.32 to 1.60. Subjects with gas or fume exposure had relative odds of symptoms between 1.27 and 1.43 when compared to unexposed subjects. Occupational dust exposure was associated with a higher prevalence of chronic obstructive pulmonary disease (COPD) as defined by an FEV1/FVC ratio of less than 0.6, when comparing exposed and unexposed participants (OR=1.53, 95% CI=1.17-2.08). Gas or fume exposure was associated with a small, but not significant, increase in COPD prevalence. Significant trends were noted for wheeze and phlegm with increasing duration of dust exposure. Although 36% of exposed subjects reported exposure to both dust and fumes, there was no evidence of a multiplicative interaction between the effects of the individual exposures. Smoking was a significant independent predictor of symptoms, but did not appear to modify the effect of dust or fumes on symptom reporting. These data, obtained in random samples of general populations, demonstrate that chronic respiratory disease can be independently associated with occupational exposures.« less

Occupational exposures and chronic respiratory symptoms. A population-based study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korn, R.J.; Dockery, D.W.; Speizer, F.E.

1987-08-01

Data from a random sample of 8515 white adults residing in 6 cities in the eastern and midwestern United States were used to examine the relationships between occupational exposures to dust or to gases and fumes and chronic respiratory symptoms; 31% of the population had a history of occupational dust exposure and 30% reported exposure to gas or fumes. After adjusting for smoking habits, age, gender, and city of residence, subjects with either occupational exposure had significantly elevated prevalences of chronic cough, chronic phlegm, persistent wheeze, and breathlessness. The adjusted relative odds of chronic respiratory symptoms for subjects exposed tomore » dust ranged from 1.32 to 1.60. Subjects with gas or fume exposure had relative odds of symptoms between 1.27 and 1.43 when compared with unexposed subjects. Occupational dust exposure was associated with a higher prevalence of chronic obstructive pulmonary disease as defined by an FEV1/FVC ratio of less than 0.6, when comparing exposed and unexposed participants (OR = 1.53, 95% Cl = 1.17-2.08). Gas or fume exposure was associated with a small, but not significant, increase in COPD prevalence. Significant trends were noted for wheeze and phlegm with increasing duration of dust exposure. Although 36% of exposed subjects reported exposure to both dust and fumes, there was no evidence of a multiplicative interaction between the effects of the individual exposures. Smoking was a significant independent predictor of symptoms, but did not appear to modify the effect of dust or fumes on symptom reporting. These data, obtained in random samples of general populations, demonstrate that chronic respiratory symptoms and disease can be independently associated with occupational exposures.« less

Effects of Chronic Ethanol Consumption on Rat GABAA and Strychnine-sensitive Glycine Receptors Expressed by Lateral/Basolateral Amygdala Neurons

PubMed Central

McCool, Brian A.; Frye, Gerald D.; Pulido, Marisa D.; Botting, Shaleen K.

2010-01-01

It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABAA and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABAA receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor’s response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABAA receptors composed of unique α subunits were differentially sensitive to acute ethanol. Likewise, the presence of the β subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the α2 subunit. Our results suggest that the facilitation of GABAA receptors during chronic ethanol exposure may help explain the maintenance of ethanol’s anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABAA and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure. PMID:12560122

Effects of chronic ethanol consumption on rat GABA(A) and strychnine-sensitive glycine receptors expressed by lateral/basolateral amygdala neurons.

PubMed

McCool, Brian A; Frye, Gerald D; Pulido, Marisa D; Botting, Shaleen K

2003-02-14

It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABA(A) and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABA(A) receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor's response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABA(A) receptors composed of unique alpha subunits were differentially sensitive to acute ethanol. Likewise, the presence of the beta subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the alpha(2) subunit. Our results suggest that the facilitation of GABA(A) receptors during chronic ethanol exposure may help explain the maintenance of ethanol's anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABA(A) and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure.

77 FR 49732 - Cyprodinil; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

.../puree (1x) and lemon/lime juice (1x) were used to modify the tolerance values. iii. Cancer. Based on the... exposure takes into account short-term residential exposure plus chronic exposure to food and water... exposure plus chronic exposure to food and water (considered to be a background exposure level). An...

Exposure to waterpipe smoke induces renal functional and oxidative biomarkers variations in mice.

PubMed

Rababa'h, Abeer M; Sultan, Bilal B; Alzoubi, Karem H; Khabour, Omar F; Ababneh, Mera A

2016-09-01

Waterpipe smoking (WPS) has been known for over 400 years. It has been spread widely especially between youth because of the addition of pleasant flavor and because it was misconsidered to be less harmful than cigarette. In this study, we investigated the effect of waterpipe smoking on renal oxidative and functional parameters and compared that at acute and chronic exposure time in mice. Mice were divided into three groups, namely acute, chronic and fresh air control. Acute group was exposed to waterpipe smoke for one hour daily for six days using whole-body exposure system, while chronic group was exposed to waterpipe smoke for one hour daily for 30 days using whole-body exposure system. Exposure to waterpipe smoke has shown significant changes on the mice kidney functional parameters such as creatinine and blood urea nitrogen. Both exposures (acute and chronic) has shown a significant reduction in superoxide dismutase (SOD) activity (p < 0.05), whereas the activity of other antioxidant enzymes (catalase and GPx) reduced only with chronic exposure to waterpipe smoke (p < 0.05). Additionally, the level of thiobarbituric acid reactive substances (TBARS) in mice kidney homogenates has shown a significant elevation following chronic exposure to waterpipe smoke (p < 0.05). In conclusion, chronic waterpipe smoke affects the kidney parameter and antioxidant markers, therefore affecting its functionality of detoxifying and removal of poisonous material from the body.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

USGS Publications Warehouse

Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.

PubMed

Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances; Hansen, John D; Kendrick, Preston S; Beyer, Richard P; Bammler, Theo K; Farin, Frederico M; Hiolski, Emma M; Smith, Donald R; Marcinek, David J

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

PATTERN OF CHOLINESTERASE INHIBITION IN ADULT, MALE RATS CHRONICALLY EXPOSED TO DIETARY CHLORPYRIFOS.

EPA Science Inventory

Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to higher, intermittent exposure of the same compound for the same duration. To that end, we exposed adult male ra...

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.

PubMed

Lundgaard, Iben; Wang, Wei; Eberhardt, Allison; Vinitsky, Hanna Sophia; Reeves, Benjamin Cameron; Peng, Sisi; Lou, Nanhong; Hussain, Rashad; Nedergaard, Maiken

2018-02-02

Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1.5 g/kg ethanol increased GFAP expression and induced mislocation of the astrocyte-specific water channel aquaporin 4 (AQP4), but decreased the levels of several cytokines. Surprisingly, glymphatic function increased in mice treated with 0.5 g/kg (low dose) ethanol following acute exposure, as well as after one month of chronic exposure. Low doses of chronic ethanol intake were associated with a significant decrease in GFAP expression, with little change in the cytokine profile compared with the saline group. These observations suggest that ethanol has a J-shaped effect on the glymphatic system whereby low doses of ethanol increase glymphatic function. Conversely, chronic 1.5 g/kg ethanol intake induced reactive gliosis and perturbed glymphatic function, which possibly may contribute to the higher risk of dementia observed in heavy drinkers.

Telomere length is a biomarker of cumulative oxidative stress, biologic age, and an independent predictor of survival and therapeutic treatment requirement associated with smoking behavior.

PubMed

Babizhayev, Mark A; Savel'yeva, Ekaterina L; Moskvina, Svetlana N; Yegorov, Yegor E

2011-11-01

Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10(16) radicals per cigarette (or 5 × 10(14) per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical population groups described in this study including elderly support the hypothesis that telomere length is a predictor of survival and therapeutic treatment requirement associated with smoking behavior.

77 FR 75855 - Spirotetramat; Pesticide Tolerance for Emergency Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

..., grape and tomato juice, applesauce, and dried apples, and Dietary Exposure Evaluation Model (DEEM (Ver... into account short-term and intermediate- term residential exposure plus chronic exposure to food and... based on short-term or intermediate-term residential exposure plus chronic dietary exposure. Because...

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER BRAINSTEM AUDITORY EVOKED RESPONSE (BAERS) IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in auditory structures in the periphery and the brainstem and is altered following chlorpyrifos exposure. This study e...

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population.

PubMed

Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P

2009-01-01

Innovative Vision Products, Inc. (IVP)'s scientists developed the lubricant eye drops (Can-C) designed as 1% N-acetylcarnosine (NAC) prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C eye drops. In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients' glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C eye drops since December 2001. Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients' compliance rate to self-administer NAC eye-drops. The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic drug studies. The authors present evidence, about why only a certain kind of NAC is safe, and why only certain formulas designed by IVP for drug discovery are efficacious in the prevention and treatment of senile cataract for long-term use. Overall cumulated studies demonstrate that the designed by IVP new vision-saving drug NAC eye drops help the aging eye to recover by improving its clarity, glare sensitivity, color perception and overall vision.

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population

PubMed Central

Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P

2009-01-01

Background: Innovative Vision Products, Inc. (IVP)’s scientists developed the lubricant eye drops (Can-C™) designed as 1% N-acetylcarnosine (NAC) prodrug of l-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural l-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops. Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. Patients or other participants: The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C™ eye drops since December 2001. Intervention: Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients’ compliance rate to self-administer NAC eye-drops. Main outcome measure and results: The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic drug studies. Conclusion: The authors present evidence, about why only a certain kind of NAC is safe, and why only certain formulas designed by IVP for drug discovery are efficacious in the prevention and treatment of senile cataract for long-term use. Overall cumulated studies demonstrate that the designed by IVP new vision-saving drug NAC eye drops help the aging eye to recover by improving its clarity, glare sensitivity, color perception and overall vision. PMID:19503764

Ocular drug metabolism of the bioactivating antioxidant N-acetylcarnosine for vision in ophthalmic prodrug and codrug design and delivery.

PubMed

Babizhayev, Mark A

2008-10-01

The basic idea in this study relates to the interesting research problem to employ with the knowledgeable pharmacy staff N-acetylcarnosine (NAC) in the developed suitable compounded prodrug ophthalmic preparations, which are currently used for the treatment of cataract and have antioxidant effect, in order to provide the molecular support to one of the most popular beliefs of the growing market for the treatment of senile cataract in patients and animals with efficacious NAC drug formulations worldwide patented by the author. This work presents the progress in ocular NAC prodrug and codrug design and delivery in light of revealed ocular metabolic activities. There is a considerable interest in the ophthalmic codrug design including NAC prodrug based on the strategies to improve ophthalmic drug delivery of the active peptide principal L-carnosine through the sustained intraocular metabolic activation of a dipeptide while making it resistant to enzymatic hydrolysis. Novel approaches to ocular NAC drug delivery, developed by Innovative Vision Products, Inc. (IVP), aim at enhancing the drug bioavailability by ensuring a prolonged retention of the medication in the eye, and/or by facilitating transcorneal penetration. IVP team studied the effects of lubricant eye drops designed as 1% NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based and corneal absorption promoters in a drug delivery system. The predicted responses of the corneal and conjunctival penetrations to the synergistic promoters are useful in controlling the extent and pathway of the ocular and systemic absorptions of instilled NAC prodrug in designed ophthalmic formulations thereof. Utility of peptidase enzyme inhibitors in the codrug formulation to modulate the transport and metabolism of NAC prodrug appears to be a promising strategy for enhancing dipeptide drug transport across the cornea. The developed and officially CE mark registered by IVP NAC prodrug and codrug lubricating eye drop systems (including principal regulatory registered eye drops design and lubricating eye drops marketed under numerous brand labels), increase the intraocular uptake of the active principle L-carnosine from its ophthalmic carrier NAC in the aqueous humor and the permeability of a drug into the eye, and so enhance the ocular bioavailability, bioactivating universal antioxidant, and anti-cataract efficacy (in human and in canine eyes) of the developed NAC eye drops.

Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

PubMed

Bahi, Amine

2013-07-01

Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

The impact of exposure to radio frequency electromagnetic fields on chronic well-being in young people--a cross-sectional study based on personal dosimetry.

PubMed

Heinrich, Sabine; Thomas, Silke; Heumann, Christian; von Kries, Rüdiger; Radon, Katja

2011-01-01

A possible influence of radio frequency electromagnetic field (RF EMF) exposure on health outcomes was investigated in various studies. The main problem of previous studies was exposure assessment. The aim of our study was the investigation of a possible association between RF EMF and chronic well-being in young persons using personal dosimetry. 3022 children and adolescents were randomly selected from the population registries of four Bavarian cities in Germany (participation 52%). Personal interview data on chronic symptoms, socio-demographic characteristics and potential confounders were collected. A 24-h radio frequency exposure profile was generated using a personal dosimeter. Exposure levels over waking hours were expressed as mean percentage of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference level. Half of the children and nearly every adolescent owned a mobile phone which was used only for short durations per day. Measured exposure was far below the current ICNIRP reference levels. The most reported chronic symptom in children and adolescents was fatigue. No statistically significant association between measured exposure and chronic symptoms was observed. Our results do not indicate an association between measured exposure to RF EMF and chronic well-being in children and adolescents. Prospective studies investigating potential long-term effects of RF EMF are necessary to confirm our results. Copyright © 2010 Elsevier Ltd. All rights reserved.

Chronic particulate exposure, mortality and cardiovascular outcomes in the nurses health study

EPA Science Inventory

Adverse health effects of exposures to acute air pollution have been well studied. Fewer studies have examined effects of chronic exposure. Previous studies used exposure estimates for narrow time periods and were limited by the geographic distribution of pollution monitors. This...

An 'injury-time integral' model for extrapolating from acute to chronic effects of phosgene.

PubMed

Hatch, G; Kodavanti, U; Crissman, K; Slade, R; Costa, D

2001-06-01

The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the 'concentrationxtime' (CxT) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (male Fischer 344) were exposed (six hours/day) to air or 0.1, 0.2, 0.5 and 1.0 ppm of phosgene one time or on a repeated regimen for up to 12 weeks as follows: 0.1 ppm (five days/week), 0.2 ppm (five days/week), 0.5 ppm (two days/week), or 1.0 ppm (one day/week) (note that the CxT for the three highest exposures was the same). Animals were sacrificed at 4, 8, and 12 weeks during the exposure and after four weeks recovery. Bronchoalveolar lavage (BAL) was performed 18 hours after the last exposure for each time period and the BAL supernatant assayed for protein. Elevated BAL fluid protein was defined as 'acute injury', diminished response after repeated exposure was defined as 'adaptation', and increased lung hydroxyproline or trichrome staining for collagen was defined as 'chronic injury'. Results indicated that exposures that cause maximal chronic injury involve high exposure concentrations and longer times between exposures, not high CxT products. A conceptual model is presented that explains the lack of CxT correlation by the fact that adaptation reduces an 'injury-time integral' as phosgene exposure is lengthened from acute to subchronic. At high exposure concentrations, the adaptive response appears to be overwhelmed, causing a continued injury-time integral, which appears to be related to appearance of chronic injury. The adaptive response is predicted to disappear if the time between exposures is lengthened, leading to a continued high injury-time integral and chronic injury. It has generally been assumed that long, continuous exposures of rodents is a conservative approach for detecting possible chronic effects. The present study suggests that such an approach my not be conservative, but might actually mask effects that could occur under intermittent exposure conditions.

Protective effects of L-carnosine on CCl4 -induced hepatic injury in rats.

PubMed

Alsheblak, Mehyar Mohammad; Elsherbiny, Nehal M; El-Karef, Amro; El-Shishtawy, Mamdouh M

2016-03-01

The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl4)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl4, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl4, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl4-induced elevation of liver-injury parameters in serum. CAR treatment also combatted oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl4-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities.

Effect of Sex on Flavor-related and Functional Compounds in Freeze-dried Broth Made from Korean Native Chicken

PubMed Central

Jayasena, Dinesh D.; Jung, Samooel; Alahakoon, Amali U.; Nam, Ki Chang

2014-01-01

Studies on the flavour characteristics of meat-based broth, quantification of flavour-related and functional compounds, and factors affecting the availability of such compounds are minimal. The present study was designed to determine the effects of sex on flavor-related and functional compounds in freeze-dried broth (FDB) made from Korean native chickens (KNC). Male and female KNC from a commercial strain (WoorimatdagTM) were reared under similar commercial conditions. FDB was separately prepared using male and female birds aged 100 d (six birds of each sex) and analyzed for nucleotide, free amino acid, betaine, carnitine, carnosine, anserine, and creatine contents, and fatty acid composition. The levels of betaine, carnitine and creatine in FDB were not significantly different between the two sexes (p>0.05) in KNC. Carnosine and anserine were not detected in FDB samples. However, FDB from female chickens had significantly higher inosine-5-monophosphate and arachidonic acid contents than did FDB from male chickens. FDB prepared with male KNC contained higher levels of inosine, linoleic acid, glycine, alanine, lysine, and serine (p<0.05). However, glutamic acid, oleic acid, and DHA were present in comparable amounts (p>0.05) in FDB made from male and female KNC. Our findings suggest that the sex of KNC has significant effect on the contents of flavor-related compounds, but not functional compounds. PMID:26761282

A cross-sectional study of secondhand smoke exposure and respiratory symptoms in non-current smokers in the U.S. trucking industry: SHS exposure and respiratory symptoms.

PubMed

Laden, Francine; Chiu, Yueh-Hsiu; Garshick, Eric; Hammond, S Katharine; Hart, Jaime E

2013-02-01

Previous studies have suggested associations of adult exposures to secondhand smoke (SHS) with respiratory symptoms, but no study has focused on blue-collar industrial environments. We assessed the association between SHS and respiratory symptoms in 1,562 non-current smoking U.S. trucking industry workers. Information on SHS exposure and respiratory health was obtained by questionnaire. Multiple logistic regression analyses were used to assess the associations of recent and lifetime exposures to SHS with chronic phlegm, chronic cough, and any wheeze, defined by American Thoracic Society criteria. In analyses adjusted for age, gender, race, childhood SHS exposure, former smoking, pack-years of smoking and years since quitting, body mass index, job title, region of the country, and urban residence, recent exposures to SHS were associated with all three respiratory symptoms (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.00-2.13) for chronic cough, 1.55 (95% CI = 1.08-2.21) for chronic phlegm, and 1.76 (95% CI = 1.41-2.21) for any wheeze). Workplace exposure was the most important recent exposure. Childhood exposure to SHS was also associated with all three symptoms, but only statistically significantly for chronic phlegm (OR = 1.84; 95% CI = 1.24-2.75). Additional years of living with a smoker were associated with an increased risk, but there was no evidence of a dose-response, except for chronic phlegm. In this group of trucking industry workers, childhood and recent exposures to SHS were related to respiratory symptoms.

A cross-sectional study of secondhand smoke exposure and respiratory symptoms in non-current smokers in the U.S. trucking industry: SHS exposure and respiratory symptoms

PubMed Central

2013-01-01

Background Previous studies have suggested associations of adult exposures to secondhand smoke (SHS) with respiratory symptoms, but no study has focused on blue-collar industrial environments. We assessed the association between SHS and respiratory symptoms in 1,562 non-current smoking U.S. trucking industry workers. Methods Information on SHS exposure and respiratory health was obtained by questionnaire. Multiple logistic regression analyses were used to assess the associations of recent and lifetime exposures to SHS with chronic phlegm, chronic cough, and any wheeze, defined by American Thoracic Society criteria. Results In analyses adjusted for age, gender, race, childhood SHS exposure, former smoking, pack-years of smoking and years since quitting, body mass index, job title, region of the country, and urban residence, recent exposures to SHS were associated with all three respiratory symptoms (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.00-2.13) for chronic cough, 1.55 (95% CI = 1.08-2.21) for chronic phlegm, and 1.76 (95% CI = 1.41-2.21) for any wheeze). Workplace exposure was the most important recent exposure. Childhood exposure to SHS was also associated with all three symptoms, but only statistically significantly for chronic phlegm (OR = 1.84; 95% CI = 1.24-2.75). Additional years of living with a smoker were associated with an increased risk, but there was no evidence of a dose–response, except for chronic phlegm. Conclusions In this group of trucking industry workers, childhood and recent exposures to SHS were related to respiratory symptoms. PMID:23368999

CHRONIC BRONCHITIS AMONG NON-SMOKING FARM WOMEN IN THE AGRICULTURAL HEALTH STUDY

PubMed Central

Valcin, Martin; Henneberger, Paul K.; Kullman, Greg J.; Umbach, David M.; London, Stephanie J.; Alavanja, Michael CR; Sandler, Dale P.; Hoppin, Jane A.

2007-01-01

Objective To examine agricultural risk factors for chronic bronchitis among non-smoking farm women. Methods We used self-reported enrollment data from the 21,541 non-smoking women in the Agricultural Health Study to evaluate occupational risk factors for prevalent chronic bronchitis among farm women. Odds ratios (ORs) for chronic bronchitis for occupational exposures were adjusted for age, state, and related agricultural exposures. Results Applying manure and driving combines were independently associated with chronic bronchitis. Off-farm job exposures associated with chronic bronchitis were organic dusts, asbestos, gasoline, and solvents. Five pesticides were associated with chronic bronchitis after multivariate adjustment and sensitivity analyses: dichlorvos (OR=1.63, 95%CI=1.01,2.61), DDT (OR=1.67, 95%CI=1.13,2.47), cyanazine (OR=1.88, 95%CI=1.00,3.54), paraquat (OR=1.91, 95%CI=1.02,3.55), and methyl bromide (OR=1.82, 95%CI=1.02,3.24). Conclusion Pesticides as well as grain and dust exposures were associated with chronic bronchitis among non-smoking farm women. PMID:17495700

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

PubMed Central

Martin, Ciara A.; Barajas, Angel; Lawless, George; Lawal, Hakeem O.; Assani, Khadij; Lumintang, Yosephine P.; Nunez, Vanessa; Krantz, David E.

2014-01-01

The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination. PMID:25160001

Estimated effect of ventilation and filtration on chronic health risks in U.S. offices, schools, and retail stores.

PubMed

Chan, W R; Parthasarathy, S; Fisk, W J; McKone, T E

2016-04-01

We assessed the chronic health risks from inhalation exposure to volatile organic compounds (VOCs) and particulate matter (PM2.5) in U.S. offices, schools, grocery, and other retail stores and evaluated how chronic health risks were affected by changes in ventilation rates and air filtration efficiency. Representative concentrations of VOCs and PM2.5 were obtained from available data. Using a mass balance model, changes in exposure to VOCs and PM2.5 were predicted if ventilation rate were to increase or decrease by a factor of two, and if higher efficiency air filters were used. Indoor concentrations were compared to health guidelines to estimate percentage exceedances. The estimated chronic health risks associated with VOC and PM2.5 exposures in these buildings were low relative to the risks from exposures in homes. Chronic health risks were driven primarily by exposures to PM2.5 that were evaluated using disease incidence of mortality, chronic bronchitis, and non-fatal stroke. The leading cancer risk factor was exposure to formaldehyde. Using disability-adjusted life years (DALYs) to account for both cancer and non-cancer effects, results suggest that increasing ventilation alone is ineffective at reducing chronic health burdens. Other strategies, such as pollutant source control and the use of particle filtration, should also be considered. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review.

PubMed

Muñoz-Quezada, María Teresa; Lucero, Boris Andrés; Iglesias, Verónica Paz; Muñoz, María Pía; Cornejo, Claudia Alejandra; Achu, Eduardo; Baumert, Brittney; Hanchey, Arianna; Concha, Carlos; Brito, Ana María; Villalobos, Marcos

2016-01-01

Previous studies have demonstrated that acute poisoning from exposure to organophosphate (OP) pesticides in agricultural workers causes adverse health effects. However, neuropsychological and cognitive effects of chronic occupational exposure to OP pesticides remain controversial. To identify, evaluate, and systematize existing evidence regarding chronic exposure to OP pesticides and neuropsychological effects in farmworkers. Using the PubMed search engine, a systematic review process was implemented and replicated according to the PRISMA statement. Eligibility criteria included workers over 18 years of age exposed to OP pesticides as well as assessment of neuropsychological and cognitive functioning. Search terms were in English and Spanish languages and included organophosphate and workers. Of the search results, 33 of 1,256 articles meet eligibility criteria. Twenty-four studies found an association between chronic occupational exposure to OP pesticides and low neuropsychological performance in workers. We classified nine of the studies to have study design limitations. Studies indicated occupational exposure to OP pesticides is linked to difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual-spatial functioning, and coordination. Nine studies find no relationship between OP pesticides exposure and neuropsychological performance. Overall, evidence suggests an association between chronic occupational exposure to OP pesticides and neuropsychological effects. However, there is no consensus about the specific cognitive skills affected.

Mechanisms Mediating Vibration-induced Chronic Musculoskeletal Pain Analyzed in the Rat

PubMed Central

Dina, Olayinka A.; Joseph, Elizabeth K.; Levine, Jon D.; Green, Paul G.

2009-01-01

While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60–80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a pro-inflammatory cytokine or re-exposure to vibration. Exposure of a hind limb to vibration produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for ~2 weeks. When nociceptive thresholds had returned to baseline, exposure to a pro-inflammatory cytokine or re-exposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia induced by vibration was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cε, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-α (TNFα) receptor. Finally, in TNFα-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. Perspective These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFα and the second messenger PKCε as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. PMID:19962353

[The remote effects of chronic exposure to ionizing radiation and electromagnetic fields with respect to hygienic standardization].

PubMed

Grigor'ev, Iu G; Shafirkin, A V; Nikitina, V N; Vasin, A L

2003-01-01

A variety and rate of non-cancer diseases occurred in humans as a result of chronic exposure to ionizing radiation or to electromagnetic radiation (EMR) of high and superhigh frequency have been compared. The intensity of EMR was slightly higher than a sanitary standard for population. A risk of health impairments in workers having occupational exposure to EMR was assessed on the basis of Selie's concept of development of non-specific reaction of the body to chronic stress factors (general adaptation syndrome), models of changes in the body compensatory reserves and calculations of radiation risk after severe and chronic exposure to ionizing radiation.

Tolerance and sensitization to chronic escalating-dose heroin following extended withdrawal in Fischer rats: possible role of mu-opioid receptors

PubMed Central

Seip-Cammack, Katharine M.; Reed, Brian; Zhang, Yong; Ho, Ann; Kreek, Mary Jeanne

2012-01-01

Rationale/objectives Heroin addiction is characterized by recurrent cycles of drug use, abstinence and relapse. It is likely that neurobiological changes during chronic heroin exposure persist across withdrawal and impact behavioral responses to re-exposure. We hypothesized that, after extended withdrawal, heroin-withdrawn rats would express behavioral tolerance and/or sensitization in response to heroin re-exposure and that these responses might be associated with altered mu-opioid receptor (MOPr) activity. Methods Male Fischer rats were exposed chronically to escalating doses of heroin (7.5–75mg/kg/day), experienced acute spontaneous withdrawal and extended (10-day) abstinence, and were re-exposed chronically to heroin. Homecage behaviors and locomotor activity in response to heroin, as well as somatic withdrawal signs, were recorded. Separate groups of rats were sacrificed after extended abstinence and MOPr expression and G-protein coupling were analyzed using [3H]DAMGO and [35S]GTPγS assays. Results The depth of behavioral stupor was lower during the initial days of heroin re-exposure compared to the initial days of the first exposure period. Behavioral responses (e.g., stereotypy) and locomotion were elevated in response to heroin re-exposure at low doses. Rats conditioned for heroin place preference during the chronic re-exposure period expressed heroin preference during acute withdrawal; this preference was stronger than rats conditioned during chronic heroin exposure that followed chronic saline and injection-free periods. Extended withdrawal was associated with increased MOPr expression in the caudate-putamen and frontal and cingulate cortices. No changes in G-protein coupling were identified. Conclusions Aspects of tolerance/sensitization to heroin are present even after extended abstinence and may be associated with altered MOPr density. PMID:22829433

Minimizing Exposure at Work

Science.gov Websites

; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure (chronic) exposure to certain pesticides may increase your risk of chronic health effects. Therefore, it is

ANIMAL MODELS OF CHRONIC PESTICIDE NEUROTOXICITY.

EPA Science Inventory

There is a wealth of literature on neurotoxicological outcomes of acute and short-term exposure to pesticides in laboratory animals, but there are relatively few studies of- long-term exposure. Many reports in the literature describing ;chronic' exposures to pesticides are, in fa...

ANIMAL MODELS OF CHRONIC PESTICIDE NEUROTOXICITY.

EPA Science Inventory

There is a wealth of literature on neurotoxicological outcomes of acute and short-term exposure to pesticides in laboratory animals, but there are relatively few reports of long-term exposure. Reports in the literature describing "chronic" exposures to pesticides are, in fact, a...

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

PubMed

Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2015-01-01

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish

PubMed Central

Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2015-01-01

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

Influence of Regularity of Exposure to Chronic Stress on the Pattern of Habituation of Pituitary-Adrenal Hormones, Prolactin and Glucose.

PubMed

Martí; Armario

1997-05-01

The effect of regularity of exposure to two different chronic stressors (noise or immobilization (IMO)) on the pattern of habituation of pituitary-adrenal (PA) hormones, prolactin and glucose was evaluated in adult male rats. Animals were chronically subjected to either regular or irregular time schedule of noise (30 min/day) or IMO (2 h/day) for two weeks. The day after the last stress session the rats were killed without stress or after having been subjected to 30 min of the homotypic stressor. Whereas regular noise did not affect food intake, body weight gain or adrenal weight, irregular noise decreased body weight gain and induced a moderate adrenal hypertrophy. In addition, previous daily exposure to regular but not to irregular noise reduced both prolactin and corticosterone responses to acute noise. In contrast, glucose response to acute noise was reduced after both regular and irregular exposure to chronic noise. Either regular or irregular exposure to chronic IMO decreased food intake and body weight and increased adrenal weight to the same extent. Likewise, no influence of regularity of exposure to chronic IMO on corticosterone and prolactin responses to acute IMO was observed. However, habituation of the ACTH response to acute IMO was observed in rats subjected to chronic regular IMO, but not in rats subjected to chronic irregular IMO. Finally, acute IMO-induced hyperglycemia diminished to the same extent after regular and irregular IMO. From these results we can conclude that: first, the process of habituation of the PA axis to chronic stress is greatly dependent upon factors such as regularity of exposure to the stressor and stressor intensity, and second, the influence of regularity on the pattern of habituation to a repeated stressor is dependent on the physiological variable we are dealing with.

Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cartularo, Laura; Laulicht, Freda; Sun, Hong

Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the Earth's crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24 h; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181more » genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24 h indicated a reduction in global levels of histone methylation and acetylation that persisted 72 h post-treatment. - Highlights: • A common route of human exposure to the carcinogenic metal cadmium is via diet. • HepG2 cells were treated acutely or chronically with varying doses of cadmium. • Gene expression analysis was performed using Affymetrix Human Gene 1.0 Arrays. • Acute and chronic exposures altered the expression of 333 and 181 genes, respectively. • Acute cadmium exposure altered global levels of histone methylation and acetylation.« less

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

PubMed

Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

2016-12-01

Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

PubMed Central

Kim, Sae-Hoon; Park, Da-Eun; Lee, Hyun-Seung; Kang, Hye-Ryun; Cho, Sang-Heon

2014-01-01

Background Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). Methods Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. Results Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. Conclusion Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. PMID:25202911

Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review

PubMed Central

Lucero, Boris Andrés; Iglesias, Verónica Paz; Muñoz, María Pía; Cornejo, Claudia Alejandra; Achu, Eduardo; Baumert, Brittney; Hanchey, Arianna; Concha, Carlos; Brito, Ana María; Villalobos, Marcos

2016-01-01

Background Previous studies have demonstrated that acute poisoning from exposure to organophosphate (OP) pesticides in agricultural workers causes adverse health effects. However, neuropsychological and cognitive effects of chronic occupational exposure to OP pesticides remain controversial. Objective To identify, evaluate, and systematize existing evidence regarding chronic exposure to OP pesticides and neuropsychological effects in farmworkers. Methods Using the PubMed search engine, a systematic review process was implemented and replicated according to the PRISMA statement. Eligibility criteria included workers over 18 years of age exposed to OP pesticides as well as assessment of neuropsychological and cognitive functioning. Search terms were in English and Spanish languages and included organophosphate and workers. Results Of the search results, 33 of 1,256 articles meet eligibility criteria. Twenty-four studies found an association between chronic occupational exposure to OP pesticides and low neuropsychological performance in workers. We classified nine of the studies to have study design limitations. Studies indicated occupational exposure to OP pesticides is linked to difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual–spatial functioning, and coordination. Nine studies find no relationship between OP pesticides exposure and neuropsychological performance. Conclusions Overall, evidence suggests an association between chronic occupational exposure to OP pesticides and neuropsychological effects. However, there is no consensus about the specific cognitive skills affected. PMID:27128815

Chronic Respiratory Symptoms and Lung Function in Agricultural Workers - Influence of Exposure Duration and Smoking.

PubMed

Stoleski, Saso; Minov, Jordan; Mijakoski, Dragan; Karadzinska-Bislimovska, Jovanka

2015-03-15

Job exposure in agricultural workers often leads to respiratory impairment. To assess the influence of exposure duration and smoking on chronic respiratory symptoms and ventilatory capacity in agricultural workers. A cross-sectional study covered 75 agricultural workers, compared with an equal number of office workers matched by age, exposure duration and smoking status. Standardized questionnaire was used to obtain data on chronic respiratory symptoms, job and smoking history. Lung functional testing was performed by spirometry. The prevalence of respiratory symptoms was higher in agricultural workers, with significant difference for cough (P = 0.034), and dyspnea (P = 0.028). Chronic respiratory symptoms among agricultural workers were significantly associated with duration of exposure (P < 0.05) and daily smoking (P < 0.01), as well as with daily smoking in controls (P < 0.01). The average values of spirometric parameters in exposed workers were significantly different for MEF50 (P = 0.002), MEF75 (P = 0.000), and MEF25-75 (P = 0.049). Obstructive changes in small airways in exposed workers were strongly related to exposure duration (P < 0.05) and smoking (P < 0.01). Agricultural workers with job exposure more than 15 years had more expressed adverse respiratory symptoms and lung function decline. The results confirmed the influence of agricultural exposure and daily smoking on chronic respiratory symptoms and airflow limitation, primarily targeting the small airways.

Associations between chronic community noise exposure and blood pressure at rest and during acute noise and non-noise stressors among urban school children in India.

PubMed

Lepore, Stephen J; Shejwal, Bhaskar; Kim, Bang Hyun; Evans, Gary W

2010-09-01

The present study builds on prior research that has examined the association between children's chronic exposure to community noise and resting blood pressure and blood pressure dysregulation during exposure to acute stressors. A novel contribution of the study is that it examines how chronic noise exposure relates to blood pressure responses during exposure to both noise and non-noise acute stressors. The acute noise stressor was recorded street noise and the non-noise stressor was mental arithmetic. The sample consisted of 189 3rd and 6th grade children (51.9% percent boys; 52.9% 3rd graders) from a noisy (n = 95) or relatively quiet (n = 94) public school in the city of Pune, India. There were no statistically significant differences between chronic noise levels and resting blood pressure levels. However, relative to quiet-school children, noisy-school children had significantly lower increases in blood pressure when exposed to either an acute noise or non-noise stressor. This finding suggests that chronic noise exposure may result in hypo-reactivity to a variety of stressors and not just habituation to noise stressors.

Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

PubMed

Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

2015-01-02

Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

Geochemical legacies and the future health of cities: A tale of two neurotoxins in urban soils

USGS Publications Warehouse

Fillipelli, Gabriel M.; Risch, Martin R.; Laidlaw, Mark A. S.; Nichols, Deborah E.; Crewe, Julie

2015-01-01

Acute exposure to lead (Pb), a powerful neurotoxin to which children are particularly susceptible, has largely been eliminated in the U.S. and other countries through policy-based restrictions on leaded gasoline and lead-based paints. But the legacy of these sources remains in the form of surface soil Pb contamination, a common problem in cities and one that has only recently emerged as a widespread chronic exposure mechanism in cities. Some urban soils are also contaminated with another neurotoxin, mercury (Hg). The greatest human exposure to Hg is through fish consumption, so eating fish caught in urban areas presents risks for toxic Hg exposure. The potential double impact of chronic exposure to these two neurotoxins is pronounced in cities. Overall, there is a paradigmatic shift from reaction to and remediation of acute exposures towards a more nuanced understanding of the dynamic cycling of persistent environmental contaminants with resultant widespread and chronic exposure of inner-city dwellers, leading to chronic toxic illness and disability at substantial human and social cost.

Characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series.

PubMed

Shively, Sharon Baughman; Horkayne-Szakaly, Iren; Jones, Robert V; Kelly, James P; Armstrong, Regina C; Perl, Daniel P

2016-08-01

No evidence-based guidelines are available for the definitive diagnosis or directed treatment of most blast-associated traumatic brain injuries, partly because the underlying pathology is unknown. Moreover, few neuropathological studies have addressed whether blast exposure produces unique lesions in the human brain, and if those lesions are comparable with impact-induced traumatic brain injury. We aimed to test the hypothesis that blast exposure produces unique patterns of damage, differing from that associated with impact-induced, non-blast traumatic brain injuries. In this post-mortem case series, we investigated several features of traumatic brain injuries, using clinical histopathology techniques and markers, in brain specimens from male military service members with chronic blast exposures and from those who had died shortly after severe blast exposures. We then compared these results with those from brain specimens from male civilian (ie, non-military) cases with no history of blast exposure, including cases with and without chronic impact traumatic brain injuries and cases with chronic exposure to opiates, and analysed the limited associated clinical histories of all cases. Brain specimens had been archived in tissue banks in the USA. We analysed brain specimens from five cases with chronic blast exposure, three cases with acute blast exposure, five cases with chronic impact traumatic brain injury, five cases with exposure to opiates, and three control cases with no known neurological disorders. All five cases with chronic blast exposure showed prominent astroglial scarring that involved the subpial glial plate, penetrating cortical blood vessels, grey-white matter junctions, and structures lining the ventricles; all cases of acute blast exposure showed early astroglial scarring in the same brain regions. All cases of chronic blast exposure had an antemortem diagnosis of post traumatic stress disorder. The civilian cases, with or without history of impact traumatic brain injury or a history of opiate use, did not have any astroglial scarring in the brain regions analysed. The blast exposure cases showed a distinct and previously undescribed pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and at junctions between grey and white matter. This distinctive pattern of scarring may indicate specific areas of damage from blast exposure consistent with the general principles of blast biophysics, and further, could account for aspects of the neuropsychiatric clinical sequelae reported. The generalisability of these findings needs to be explored in future studies, as the number of cases, clinical data, and tissue availability were limited. Defense Health Program of the United States Department of Defense. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vapor, Dust and Smoke Exposure in relation to adult-onset asthma and chronic respiratory symptoms: The Singapore Chinese Health Study

PubMed Central

LeVan, Tricia D.; Koh, Woon-Puay; Lee, Hin-Peng; Koh, David; Yu, Mimi C.; London, Stephanie J.

2006-01-01

Occupational factors contribute to a significant fraction of respiratory disease and symptoms. We evaluated the role of occupational exposures on asthma, chronic bronchitis, and respiratory symptoms in a population-based cohort, the Singapore Chinese Health Study. History of occupations, occupational exposures, and respiratory conditions were collected by interviews with 52,325 Singaporeans born 1918–1953. Exposure to dusts, from cotton, wood, metal, mineral and/or asbestos, was associated with non-chronic cough and/or phlegm (OR = 1.19, 95% CI = 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI = 1.01, 1.57) and adult-onset asthma (OR = 1.14, 95% CI = 1.00, 1.30). Cotton dust was the major component contributing to respiratory symptoms. Vapor exposure, from chemical solvents, dyes, cooling oils, paints, wood preservatives and/or pesticides, was associated with non-chronic cough or phlegm (OR = 1.14, 95% CI = 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI = 1.19, 2.01) and adult-onset asthma (OR = 1.34, 95% CI = 1.15, 1.56). Chemical solvents, cooling oils and pesticides were the major sources contributing to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness. PMID:16707657

Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.

PubMed

Hillmer, Ansel T; Tudorascu, Dana L; Wooten, Dustin W; Lao, Patrick J; Barnhart, Todd E; Ahlers, Elizabeth O; Resch, Leslie M; Larson, Julie A; Converse, Alexander K; Moore, Colleen F; Schneider, Mary L; Christian, Bradley T

2014-05-01

The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake. [(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol. Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking. The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Oral exposure to polystyrene nanoparticles effects iron absorption

USDA-ARS?s Scientific Manuscript database

The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron trans...

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: I. BIOMARKERS FOR ASSESSING EXPOSURE AND EFFECTS

EPA Science Inventory

Health Effects of Chronic Exposure to Arsenic via Drinking Water in Inner Mongolia: I. Biomarkers for Assessing Exposure and Effects

Judy L. Mumford, Ph.D., Mike Schmitt, M.S.P.H., Richard K. Kwok, M.S.P.H., Rebecca Calderon, Ph.D., National Health and Environmental Effect...

The Longitudinal Effects of Chronic Mediated Exposure to Political Violence on Ideological Beliefs About Political Conflicts Among Youths.

PubMed

Gvirsman, Shira Dvir; Huesmann, L Rowell; Dubow, Eric F; Landau, Simha F; Boxer, Paul; Shikaki, Khalil

This study examines the effects of chronic (i.e., repeated and cumulative) mediated exposure to political violence on ideological beliefs regarding political conflict. It centers on these effects on young viewers, from preadolescents to adolescents. Ideological beliefs refers here to support of war, perception of threat to one's nation, and normative beliefs concerning aggression toward the out-group. A longitudinal study was conducted on a sample of Israeli and Palestinian youths who experience the Israeli-Palestinian conflict firsthand ( N = 1,207). Two alternative hypotheses were tested: that chronic exposure via the media increases support for war and aggression and elevates feeling of threat, or that chronic exposure via the media strengthens preexisting beliefs. Results demonstrated that higher levels of exposure were longitudinally related to stronger support for war. Regarding normative beliefs about aggression and threat to one's nation, mediated exposure reinforced initial beliefs, rendering the youths more extreme in their attitudes. These results mostly support the conceptualization of the relation between media violence and behaviors as "reciprocally determined" or "reinforcing spirals." The results are also discussed in light of the differences found between the effect of exposure to political violence firsthand and exposure via the media.

Biological functions of histidine-dipeptides and metabolic syndrome.

PubMed

Song, Byeng Chun; Joo, Nam-Seok; Aldini, Giancarlo; Yeum, Kyung-Jin

2014-02-01

The rapid increase in the prevalence of metabolic syndrome, which is associated with a state of elevated systemic oxidative stress and inflammation, is expected to cause future increases in the prevalence of diabetes and cardiovascular diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive carbonyl species, which, due to their electrophilic nature, react with the nucleophilic sites of certain amino acids. This leads to formation of protein adducts such as advanced glycoxidation/lipoxidation end products (AGEs/ALEs), resulting in cellular dysfunction. Therefore, an effective reactive carbonyl species and AGEs/ALEs sequestering agent may be able to prevent such cellular dysfunction. There is accumulating evidence that histidine containing dipeptides such as carnosine (β-alanyl-L-histidine) and anserine (β-alanyl-methyl-L-histidine) detoxify cytotoxic reactive carbonyls by forming unreactive adducts and are able to reverse glycated protein. In this review, 1) reaction mechanism of oxidative stress and certain chronic diseases, 2) interrelation between oxidative stress and inflammation, 3) effective reactive carbonyl species and AGEs/ALEs sequestering actions of histidine-dipeptides and their metabolism, 4) effects of carnosinase encoding gene on the effectiveness of histidine-dipeptides, and 5) protective effects of histidine-dipeptides against progression of metabolic syndrome are discussed. Overall, this review highlights the potential beneficial effects of histidine-dipeptides against metabolic syndrome. Randomized controlled human studies may provide essential information regarding whether histidine-dipeptides attenuate metabolic syndrome in humans.

SOURCES AND ESTIMATED LOAD OF BIOAVAILABLE NITROGEN ATTRIBUTABLE TO CHRONIC NITROGEN EXPOSURE AND CHANGED ECOSYSTEM STRUCTURE AND FUNCTION

EPA Science Inventory

Bioavailable nitrogen is a limiting nutrient throughout the Eastern United States. Research demonstrates that exposure to large doses of nitrogen leads to deleterious environmental impacts. However, effects of chronic exposure to lower doses of nitrogen are not well known. Since...

Development of a Complete Life Cycle Sediment Toxicity Test for the Sheepshead Minnow (Cyprinodon variegatus)

EPA Science Inventory

Existing sediment toxicity test methods are limited to acute and chronic exposure of invertebrates and acute exposure of vertebrates, with limited guidance on the chronic exposure of vertebrates, specifically fishes. A series of life stage-specific studies were conducted to dete...

SOURCES AND ESTIMATED LOAD OF BIOAVAILABLE NITROGEN ATTRIBUTED TO CHRONIC NITROGEN EXPOSURE AND CHANGED ECOSYSTEM STRUCTURE AND FUNCTION

EPA Science Inventory

Bioavailable nitrogen is a limiting nutrient throughout the Eastern United States. Research demonstrates that exposure to large doses of nitrogen leads to deleterious environmental impacts. However, effects of chronic exposure to lower doses of nitrogen are under-appreciated. ...

Airborne particulate matter exposure and urinary albumin excretion: the Multi-Ethnic Study of Atherosclerosis

PubMed Central

O’Neill, M S; Diez-Roux, A V; Auchincloss, A H; Franklin, T G; Jacobs, D R; Astor, B C; Dvonch, J T; Kaufman, J

2010-01-01

Objectives Understanding mechanistic pathways linking airborne particle exposure to cardiovascular health is important for causal inference and setting environmental standards. We evaluated whether urinary albumin excretion, a subclinical marker of microvascular function which predicts cardiovascular events, was associated with ambient particle exposure. Methods Urinary albumin and creatinine were measured among members of the Multi-Ethnic Study of Atherosclerosis at three visits during 2000–2004. Exposure to PM2.5 and PM10 (µg/m3) was estimated from ambient monitors for 1 month, 2 months and two decades before visit one. We regressed recent and chronic (20 year) particulate matter (PM) exposure on urinary albumin/creatinine ratio (UACR, mg/g) and microalbuminuria at first examination, controlling for age, race/ethnicity, sex, smoking, second-hand smoke exposure, body mass index and dietary protein (n = 3901). We also evaluated UACR changes and development of microalbuminuria between the first, and second and third visits which took place at 1.5- to 2-year intervals in relation to chronic PM exposure prior to baseline using mixed models. Results Chronic and recent particle exposures were not associated with current UACR or microalbuminuria (per 10 µg/m3 increment of chronic PM10 exposure, mean difference in log UACR = −0.02 (95% CI −0.07 to 0.03) and relative probability of having microalbuminuria = 0.92 (95% CI 0.77 to 1.08)) We found only weak evidence that albuminuria was accelerated among those chronically exposed to particles: each 10 µg/m3 increment in chronic PM10 exposure was associated with a 1.14 relative probability of developing microalbuminuria over 3–4 years, although 95% confidence intervals included the null (95% CI 0.96 to 1.36). Conclusions UACR is not a strong mechanistic marker for the possible influence of air pollution on cardiovascular health in this sample. PMID:18032533

Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

PubMed

Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

2018-01-01

Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions between stress exposure (via glucocorticoid actions) and infection impose resource trade-offs that shape optimal allocation between development and somatic function. As a result, critical disease windows are likely shaped by stress exposure because any conditions that induce changes in differentiation rates will alter the duration and susceptibility of organisms to stressors or disease. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Low level exposure to monomethyl arsonous acid-induced the over-production of inflammation-related cytokines and the activation of cell signals associated with tumor progression in a urothelial cell model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escudero-Lourdes, C., E-mail: cescuder@uaslp.m; Medeiros, M.K.; Cardenas-Gonzalez, M.C.

2010-04-15

Human bladder cancer has been associated with chronic exposure to arsenic. Chronic exposure of an immortalized non-tumorigenic urothelial cell line (UROtsa cells) to arsenicals has transformed these cells to a malignant phenotype, but the involved mechanisms are not fully understood. Chronic inflammation has been linked with cancer development mainly because many pro-inflammatory cytokines, growth factors as well as angiogenic chemokines have been found in tumors. In this study the chronology of inflammatory cytokines production was profiled in UROtsa cells chronically exposed to the toxic arsenic metabolite, monomethylarsonous acid [50 nM MMA(III)] to know the role of inflammation in cell transformation.more » Acute 50 nM MMA(III) exposure induced over-production of many pro-inflammatory cytokines as soon as 12 h after acute exposure. The same cytokines remain over-regulated after chronic exposure to 50 nM MMA(III), especially after 3 mo exposure. At 3 mo exposure the sustained production of cytokines like IL-1, IL-6, IL-8 and TNF is coincident with the appearance of characteristics associated with cell transformation seen in other arsenic-UROtsa studies. The sustained and increased activation of NFkappaB and c-Jun is also present along the transformation process and the phosphorylated proteins p38 MAPK and ERK 1/2 are increased also through the time line. Taken together these results support the notion that chronic inflammation is associated within MMA(III)-induced cell transformation and may act as a promoting factor in UROtsa cell transformation.« less

Adaptation in Caco-2 human intestinal cell differentiation and phenolic transport with chronic exposure to phenolic-rich blackberry (Rubus sp.) extract

USDA-ARS?s Scientific Manuscript database

As evidence mounts for a health-protective role of dietary phenolics, the importance of understanding factors influencing bioavailability increases. Recent evidence has suggested chronic exposure may impact phenolic absorption and metabolism. To explore alterations occurring from chronic dietary e...

Chronic stressors and trauma: prospective influences on the course of bipolar disorder

PubMed Central

Gershon, A.; Johnson, S. L.; Miller, I.

2013-01-01

Background Exposure to life stress is known to adversely impact the course of bipolar disorder. Few studies have disentangled the effects of multiple types of stressors on the longitudinal course of bipolar I disorder. This study examines whether severity of chronic stressors and exposure to trauma are prospectively associated with course of illness among bipolar patients. Method One hundred and thirty-one participants diagnosed with bipolar I disorder were recruited through treatment centers, support groups and community advertisements. Severity of chronic stressors and exposure to trauma were assessed at study entry with in-person interviews using the Bedford College Life Event and Difficulty Schedule (LEDS). Course of illness was assessed by monthly interviews conducted over the course of 24 months (over 3000 assessments). Results Trauma exposure was related to more severe interpersonal chronic stressors. Multiple regression models provided evidence that severity of overall chronic stressors predicted depressive but not manic symptoms, accounting for 7.5% of explained variance. Conclusions Overall chronic stressors seem to be an important determinant of depressive symptoms within bipolar disorder, highlighting the importance of studying multiple forms of life stress. PMID:23419615

Chronic stressors and trauma: prospective influences on the course of bipolar disorder.

PubMed

Gershon, A; Johnson, S L; Miller, I

2013-12-01

Exposure to life stress is known to adversely impact the course of bipolar disorder. Few studies have disentangled the effects of multiple types of stressors on the longitudinal course of bipolar I disorder. This study examines whether severity of chronic stressors and exposure to trauma are prospectively associated with course of illness among bipolar patients. One hundred and thirty-one participants diagnosed with bipolar I disorder were recruited through treatment centers, support groups and community advertisements. Severity of chronic stressors and exposure to trauma were assessed at study entry with in-person interviews using the Bedford College Life Event and Difficulty Schedule (LEDS). Course of illness was assessed by monthly interviews conducted over the course of 24 months (over 3000 assessments). Trauma exposure was related to more severe interpersonal chronic stressors. Multiple regression models provided evidence that severity of overall chronic stressors predicted depressive but not manic symptoms, accounting for 7.5% of explained variance. Overall chronic stressors seem to be an important determinant of depressive symptoms within bipolar disorder, highlighting the importance of studying multiple forms of life stress.

Effects of nitrogen dioxide on pulmonary function in human subjects: an environmental chamber study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerr, H.D.; Kulle, T.J.; McIlhany, M.L.

Twenty human subjects with asthma and chronic bronchitis and 10 normal, healthy adults were exposed to 0.5 ppM of nitrogen dioxide for 2 h in an environmental chamber. Seven of the 13 subjects with asthma experienced symptoms with exposure, while only one each of the subjects with chronic bronchitis and the healthy, normal group experienced symptoms. Significant pulmonary function changes from control values with exposure to NO/sub 2/ were observed in decreased quasistatic compliance for the 10 normal subjects and the 20 subjects with asthma and chronic bronchitis. In addition, functional residual capacity increased significantly for the 20 subjects withmore » asthma and chronic bronchitis. The subjects with asthma and the subjects with chronic bronchitis as separate groups, however, did not show any significant changes with exposure. With this study we are reasonably confident that exposure of subjects with asthma and chronic bronchitis to 0.5 ppM NO/sub 2/ for 2 h does not produce a significant decrement in their pulmonary function.« less

Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.

PubMed

Hogan, Mary Beth; Piktel, Debra; Hubbs, Ann F; McPherson, Leslie E; Landreth, Kenneth S

2008-12-01

Patient factors that cause long-term airway remodeling are largely unidentified. This suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. To investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. The C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.

Occupational Risk Factors for COPD Phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

PubMed Central

Doney, Brent; Hnizdo, Eva; Graziani, Monica; Kullman, Greg; Burchfiel, Cecil; Baron, Sherry; Fujishiro, Kaori; Enright, Paul; Hankinson, John L.; Stukovsky, Karen Hinckley; Martin, Christopher J.; Donohue, Kathleen M.; Barr, R. Graham

2014-01-01

Introduction The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation. Methods We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45–84 year olds free of clinical cardiovascular disease at baseline. MESA ascertained the most recent job and employment, and the MESA Lung Study measured spirometry, and occupational exposures for 3686 participants. Associations between health outcomes (spirometry defined airflow limitation and Medical Research Council-defined chronic bronchitis) and occupational exposure [self-reported occupational exposure to vapor-gas, dust, or fumes (VGDF), severity of exposure, and a job-exposure matrix (JEM)-derived score] were evaluated using logistic regression models adjusted for non-occupational risk factors. Results The prevalence of airflow limitation was associated with self-reported exposure to vapor-gas (OR 2.6, 95%CI 1.1–2.3), severity of VGDF exposure (P-trend<0.01), and JEM dust exposure (OR 2.4, 95%CI 1.1–5.0), and with organic dust exposure in females; these associations were generally of greater magnitude among never smokers. The prevalence of chronic bronchitis and wheeze was associated with exposure to VGDF. The association between airflow limitation and the combined effect of smoking and VGDF exposure showed an increasing trend. Self-reported vapor-gas, dust, fumes, years and severity of exposure were associated with increased prevalence of chronic bronchitis and wheeze (P<0.001). Conclusions Airflow limitation was associated with self-reported VGDF exposure, its severity, and JEM-ascertained dust exposure in smokers and never-smokers in this multiethnic study. PMID:24568208

Chronic effects on JP-8 jet fuel exposure on the lungs. Final technical report, 1 April 1991-31 March 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witten, M.L.

1994-06-02

There are four major findings from the three years of work devoted to the effects of chronic JP-8 jet fuel exposure on the lungs and secondary organs. These findings are the following chronic exposure to JP-8 jet fuel alters pulmonary function and lung structures with an acute response with as little as seven days of low dose, approximately 500 mg/m3, exposure to JP-8 jet fuel; chronic exposure to JP-8 jet fuel increased liver, spleen, and kidney weights compared to controls. Microscopic evaluation of liver sections were normal; however, kidney and spleen had histological changes consistent with organic solvent exposure. Theremore » is a correlation between JP-8 jet fuel exposure-induced decreases in lung Substance P levels and lung neutral endopeptidase levels. Chronic exposure to JP-8 jet fuel caused a decrease in lung Substance P levels with a corresponding increase in lung neutral endopeptidase levels; and, there is a recovery process in the 56 day low dose JP-8 jet fuel-exposed lungs as marked by a return to baseline and longitudinal control 99mTcDTPA values. The 99mTcDTPA data was very consistent with our pathologic findings of very little lung injury in the 56 day low dose JP-8 jet fuel-exposed rats. We speculate that this finding indicates that there is a 'threshold' level of JP-8 jet fuel exposure that the lungs' defense mechanism(s) can tolerate.« less

Active war in Sri Lanka: Children's war exposure, coping, and posttraumatic stress disorder symptom severity.

PubMed

Soysa, Champika K; Azar, Sandra T

2016-01-01

Posttraumatic stress disorder (PTSD) in response to active war is understudied among Sinhalese children in Sri Lanka. We investigated PTSD symptom severity in children using child (n = 60) and mother (n = 60) reports; child-reported war exposure and coping; as well as self-reported maternal PTSD symptom severity. The study addressed active war in 2 rural locations (acute and chronic community war exposure). Child-reports were significantly greater than mother-reports of child PTSD symptom severity. Furthermore, children's war exposure, child-reported and mother-reported child PTSD symptom severity, and maternal PTSD symptom severity were significantly greater in the acute versus chronic community war exposure location, but children's approach and avoidance coping did not significantly differ, indicating a potential ceiling effect. Children's war exposure significantly, positively predicted child-reported child PTSD symptom severity, controlling for age, gender, and maternal PTSD symptom severity, but only maternal PTSD symptom severity significantly, positively predicted mother-reported child PTSD symptom severity. Avoidance coping (in both acute and chronic war) significantly positively mediated the children's war exposure-child-reported child PTSD symptom severity relation, but not mother-reports of the same. Approach coping (in chronic but not acute war) significantly, positively mediated the children's war exposure-child-reported and mother-reported child PTSD symptom severity relations. We advanced the literature on long-term active war by confirming the value of children's self-reports, establishing that both approach and avoidance coping positively mediated the war-exposure-PTSD symptom severity relation, and that the mediation effect of approach coping was situationally moderated by acute verses chronic community war exposure among Sri Lankan children. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Increased risk of QT prolongation associated with atherosclerotic diseases in arseniasis-endemic area in southwestern coast of Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, C.-H.; Chen, C.-L.; Hsiao, C.K.

2009-09-15

Chronic arsenic exposure has been documented to be associated with various cardiovascular diseases. We aimed to investigate 1) the increased risk of QT prolongation in chronic arsenic exposure, and 2) the relationships of cardiac repolarization (QT interval duration) with ischemic heart disease and carotid atherosclerosis. We studied 280 men and 355 women living in the endemic area of arseniasis in southwestern Taiwan. QT intervals in electrocardiogram and carotid intima-media thickness (IMT) by ultrasonography were measured. Ischemic heart disease was diagnosed by history or abnormal electrocardiogram. Significant associations of the corrected QT interval (QTc) duration with ischemic heart disease and carotidmore » intima-medium thickness and plaque were observed after adjustment for various risk factors in the multiple linear regression analysis (all p values < 0.05). Three indices of chronic arsenic exposure were all significantly associated with the risk of QTc prolongation showing dose-response relationships (p < 0.001). Chronic arsenic exposure was dose-dependently associated with the risk of QTc prolongation. Ischemic heart disease and carotid atherosclerosis were significantly associated with QTc intervals in chronic arsenic exposure. QTc prolongation might be suggested as an early biomarker for ischemic heart disease or carotid atherosclerosis in population with previous exposure to arsenic.« less

Occupational exposure to pesticides and respiratory health.

PubMed

Mamane, Ali; Baldi, Isabelle; Tessier, Jean-François; Raherison, Chantal; Bouvier, Ghislaine

2015-06-01

This article aims to review the available literature regarding the link between occupational exposure to pesticides and respiratory symptoms or diseases. Identification of epidemiological studies was performed using PubMed. 41 articles were included, 36 regarding agricultural workers and five regarding industry workers. Among the 15 cross-sectional studies focusing on respiratory symptoms and agricultural pesticide exposure, 12 found significant associations with chronic cough, wheeze, dyspnoea, breathlessness or chest tightness. All four studies on asthma found a relationship with occupational exposure, as did all three studies on chronic bronchitis. The four studies that performed spirometry reported impaired respiratory function linked to pesticide exposure, suggestive of either obstructive or restrictive syndrome according to the chemical class of pesticide. 12 papers reported results from cohort studies. Three out of nine found a significant relationship with increased risk of wheeze, five out of nine with asthma and three out of three with chronic bronchitis. In workers employed in pesticide production, elevated risks of chronic obstructive pulmonary disease (two studies out of three) and impaired respiratory function suggestive of an obstructive syndrome (two studies out of two) were reported. In conclusion, this article suggests that occupational exposure to pesticides is associated with an increased risk of respiratory symptoms, asthma and chronic bronchitis, but the causal relationship is still under debate. Copyright ©ERS 2015.

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure

PubMed Central

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-01-01

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N = 33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 µg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL × sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. PMID:25936521

An experimental double-blind irradiation study of a novel topical product (TPF 50) compared to other topical products with DNA repair enzymes, antioxidants, and growth factors with sunscreens: implications for preventing skin aging and cancer.

PubMed

Emanuele, Enzo; Spencer, James M; Braun, Martin

2014-03-01

The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.

Chronic respiratory effects of exposure to diesel emissions in coal mines.

PubMed

Ames, R G; Hall, D S; Reger, R B

1984-01-01

A 5-yr prospective design was employed to test the hypothesis that exposure to diesel emissions leads to chronic respiratory effects among underground coal miners. Changes in respiratory function and development of chronic respiratory symptoms were measured during a 5-yr study period (i.e., 1977 to 1982) in 280 diesel-exposed and 838 control miners from Eastern and Western United States underground coal mines. Spirometry measures of respiratory function included forced expiratory volume in 1 sec (FEV1.0), forced vital capacity (FVC), and forced expiratory flow rate at 50% of FVC (FEF50). Chronic respiratory symptom measures, which included chronic cough, chronic phlegm, and breathlessness, were obtained by questionnaires, as were smoking status and occupational history. Based upon these data, the pattern of evidence did not support the hypothesis either in an age-adjusted comparison of diesel vs. nondiesel miners or in an internal analysis by cumulative years of diesel exposure.

TOWARDS RELIABLE AND COST-EFFECTIVE OZONE EXPOSURE ASSESSMENT: PARAMETER EVALUATION AND MODEL VALIDATION USING THE HARVARD SOUTHERN CALIFORNIA CHRONIC OZONE EXPOSURE STUDY DATA

EPA Science Inventory

Accurate assessment of chronic human exposure to atmospheric criteria pollutants, such as ozone, is critical for understanding human health risks associated with living in environments with elevated ambient pollutant concentrations. In this study, we analyzed a data set from a...

Effect Of Ventilation On Chronic Health Risks In Schools And Offices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parthasarathy, Srinandini; Fisk, William J.; McKone, Thomas E.

This study provides a risk assessment for chronic health risks from inhalation exposure to indoor air pollutants in offices and schools with a focus how ventilation impacts exposures to, and risks from, volatile organic compounds (VOCs) and particulate matter (PM2.5). We estimate how much health risks could change with varying ventilation rates under two scenarios: (i) halving the measured ventilation rates and (ii) doubling the measured ventilation rates. For the hazard characterization we draw upon prior papers that identified pollutants potentially affecting health with indoor air concentrations responsive to changes in ventilation rates. For exposure assessment we determine representative concentrationsmore » of pollutants using data available in current literature and model changes in exposures with changes in ventilation rates. As a metric of disease burden, we use disability adjusted life years (DALYs) to address both cancer and non-cancer effects. We also compare exposures to guidelines published by regulatory agencies to assess chronic health risks. Chronic health risks are driven primarily by particulate matter exposure, with an estimated baseline disease burden of 150 DALYs per 100,000 people in offices and 140 DALYs per 100,000 people in schools. Study results show that PM2.5-related DALYs are not very sensitive to changes in ventilation rates. Filtration is more effective at controlling PM2.5 concentrations and health effects. Non-cancer health effects contribute only a small fraction of the overall chronic health burden of populations in offices and schools (<1 DALY per 100,000 people). Cancer health effects dominate the disease burden in schools (3 DALYs per 100,000) and offices (5 DALYs per 100,000), with formaldehyde being the primary risk driver. In spite of large uncertainties in toxicological data and dose-response modeling, our results support the finding that ventilation rate changes do not have significant impacts on estimated chronic disease burdens. Median estimates of DALYs are approximately doubled when the ventilation rates are halved and there is little reduction in health risks associated with doubling ventilation rates, but the very low baseline disease burden from the indoor exposures we considered makes this unremarkable. In exploring the full range of exposure concentrations, to find the fraction exceeding the Office of Environmental Health and Hazard Assessment’s (OEHHAs) chronic reference exposure levels (cRELs) and United States Environmental Protection Agency’s (USEPA) chronic reference dose (RfD) we found only minor shifts in exposure safety margins when ventilation was doubled or halved. We combined our exposure estimates with cancer potency factors published by OEHHA and USEPA to determine that the annual excess cancer risk per capita are below 1 in a million under all ventilation rate scenarios for individual pollutants. The results indicate that chronic health risks (cancer and non-cancer) associated with VOC and PM2.5 exposure in offices and schools are low and thus the chronic disease burden or health benefits of ventilation changes are likely to be well below both the level of detection by health surveillance studies and the level of regulatory thresholds.« less

Acute and chronic cold exposure differentially affects the browning of porcine white adipose tissue.

PubMed

Gao, Y; Qimuge, N R; Qin, J; Cai, R; Li, X; Chu, G Y; Pang, W J; Yang, G S

2018-07-01

Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal's response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed. Interestingly, acute cold exposure induced browning of porcine sWAT, smaller adipocytes and the upregulated expression of UCP1, PGC1α, PGC1β, C/EBPβ, Cidea, UCP3, CKMT1 and PM20D1. Conversely, chronic cold exposure impaired the browning process, reduced mitochondrial numbers and the expression of browning markers, including UCP1, PGC1α and PRDM16. The present study demonstrated that acute cold exposure (but not chronic cold exposure) induces porcine sWAT browning. Thus, browning of porcine sWAT could be a novel strategy to balance the body temperature of piglets, and thus could be protective against cold exposure.

The Longitudinal Effects of Chronic Mediated Exposure to Political Violence on Ideological Beliefs About Political Conflicts Among Youths

PubMed Central

Gvirsman, Shira Dvir; Huesmann, L. Rowell; Dubow, Eric F.; Landau, Simha F.; Boxer, Paul; Shikaki, Khalil

2015-01-01

This study examines the effects of chronic (i.e., repeated and cumulative) mediated exposure to political violence on ideological beliefs regarding political conflict. It centers on these effects on young viewers, from preadolescents to adolescents. Ideological beliefs refers here to support of war, perception of threat to one's nation, and normative beliefs concerning aggression toward the out-group. A longitudinal study was conducted on a sample of Israeli and Palestinian youths who experience the Israeli-Palestinian conflict firsthand (N = 1,207). Two alternative hypotheses were tested: that chronic exposure via the media increases support for war and aggression and elevates feeling of threat, or that chronic exposure via the media strengthens preexisting beliefs. Results demonstrated that higher levels of exposure were longitudinally related to stronger support for war. Regarding normative beliefs about aggression and threat to one's nation, mediated exposure reinforced initial beliefs, rendering the youths more extreme in their attitudes. These results mostly support the conceptualization of the relation between media violence and behaviors as “reciprocally determined” or “reinforcing spirals.” The results are also discussed in light of the differences found between the effect of exposure to political violence firsthand and exposure via the media. PMID:26997852

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion.

PubMed

Thurlow, John S; Little, Dustin J; Baker, Thomas P; Yuan, Christina M

2013-06-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion.

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

PubMed Central

Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

2013-01-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion. PMID:26064493

Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

USGS Publications Warehouse

Wang, Ning; Mebane, Christopher A.; Kunz, James L.; Ingersoll, Christopher G.; Brumbaugh, William G.; Santore, Robert C.; Gorsuch, Joseph W.; Arnold, W. Ray

2011-01-01

Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO3, pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15–72 μg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25–267 μg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13–61 μg Cu/L for survival; 8.8–38 μg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13–215 μg Cu/L) for survival or approximately fourfold (12–42 μg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and chronic exposure, and the cladoceran from chronic exposure.

Recent versus chronic exposure to particulate matter air pollution in association with neurobehavioral performance in a panel study of primary schoolchildren.

PubMed

Saenen, Nelly D; Provost, Eline B; Viaene, Mineke K; Vanpoucke, Charlotte; Lefebvre, Wouter; Vrijens, Karen; Roels, Harry A; Nawrot, Tim S

2016-10-01

Children's neuropsychological abilities are in a developmental stage. Recent air pollution exposure and neurobehavioral performance are scarcely studied. In a panel study, we repeatedly administered to each child the following neurobehavioral tests: Stroop Test (selective attention) and Continuous Performance Test (sustained attention), Digit Span Forward and Backward Tests (short-term memory), and Digit-Symbol and Pattern Comparison Tests (visual information processing speed). At school, recent inside classroom particulate matter ≤2.5 or 10μm exposure (PM2.5, PM10) was monitored on each examination day. At the child's residence, recent (same day up to 2days before) and chronic (365days before examination) exposures to PM2.5, PM10 and black carbon (BC) were modeled. Repeated neurobehavioral test performances (n=894) of the children (n=310) reflected slower Stroop Test (p=0.05) and Digit-Symbol Test (p=0.01) performances with increasing recent inside classroom PM2.5 exposure. An interquartile range (IQR) increment in recent residential outdoor PM2.5 exposure was associated with an increase in average latency of 0.087s (SE: ±0.034; p=0.01) in the Pattern Comparison Test. Regarding chronic exposure at residence, an IQR increment of PM2.5 exposure was associated with slower performances in the Continuous Performance (9.45±3.47msec; p=0.007) and Stroop Tests (59.9±26.5msec; p=0.02). Similar results were obtained for PM10 exposure. In essence, we showed differential neurobehavioral changes robustly and adversely associated with recent or chronic ambient exposure to PM air pollution at residence, i.e., with recent exposure for visual information processing speed (Pattern Comparison Test) and with chronic exposure for sustained and selective attention. Copyright © 2016. Published by Elsevier Ltd.

Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo.

PubMed

Abdullah, Muhammad; Kornegay, Joe N; Honcoop, Aubree; Parry, Traci L; Balog-Alvarez, Cynthia J; O'Neal, Sara K; Bain, James R; Muehlbauer, Michael J; Newgard, Christopher B; Patterson, Cam; Willis, Monte S

2017-07-29

Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10 -3 ), carnosine (0.40-fold of controls, p = 1.88 × 10 -2 ), fumaric acid (0.40-fold of controls, p = 7.40 × 10 -4 ), lactamide (0.33-fold of controls, p = 4.84 × 10 -2 ), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10 -2 ), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10 -2 ), glutamic acid (2.48-fold of controls, p = 2.63 × 10 -2 ), and proline (1.73-fold of controls, p = 3.01 × 10 -2 ). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10 -4 , FDR 4.7 × 10 -2 ), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle dysfunction. In contrast, two pathways, inosine-5'-monophosphate (VIP Score 3.91) and 3-phosphoglyceric acid (VIP Score 3.08) mainly contributed to the LDE signature, with two metabolites (phosphoglyceric acid and inosine-5'-monophosphate) being significantly decreased. When the BF and LDE were compared, the most significant metabolite was phosphoric acid, which was significantly less in the GRMD BF compared to control and GRMD LDE groups. The identification of elevated BF oleic acid (a long-chain fatty acid) is consistent with recent microarray studies identifying altered lipid metabolism genes, while alterations in arginine and proline metabolism are consistent with recent studies identifying elevated L-arginine in DMD patient sera as a biomarker of disease. Together, these studies demonstrate muscle-specific alterations in GRMD-affected muscle, which illustrate previously unidentified metabolic changes.

Neuroplasticity of A-type potassium channel complexes induced by chronic alcohol exposure enhances dendritic calcium transients in hippocampus.

PubMed

Mulholland, Patrick J; Spencer, Kathryn B; Hu, Wei; Kroener, Sven; Chandler, L Judson

2015-06-01

Chronic alcohol-induced cognitive impairments and maladaptive plasticity of glutamatergic synapses are well-documented. However, it is unknown if prolonged alcohol exposure affects dendritic signaling that may underlie hippocampal dysfunction in alcoholics. Back-propagation of action potentials (bAPs) into apical dendrites of hippocampal neurons provides distance-dependent signals that modulate dendritic and synaptic plasticity. The amplitude of bAPs decreases with distance from the soma that is thought to reflect an increase in the density of Kv4.2 channels toward distal dendrites. The aim of this study was to quantify changes in hippocampal Kv4.2 channel function and expression using electrophysiology, Ca(2+) imaging, and western blot analyses in a well-characterized in vitro model of chronic alcohol exposure. Chronic alcohol exposure significantly decreased expression of Kv4.2 channels and KChIP3 in hippocampus. This reduction was associated with an attenuation of macroscopic A-type K(+) currents in CA1 neurons. Chronic alcohol exposure increased bAP-evoked Ca(2+) transients in the distal apical dendrites of CA1 pyramidal neurons. The enhanced bAP-evoked Ca(2+) transients induced by chronic alcohol exposure were not related to synaptic targeting of N-methyl-D-aspartate (NMDA) receptors or morphological adaptations in apical dendritic arborization. These data suggest that chronic alcohol-induced decreases in Kv4.2 channel function possibly mediated by a downregulation of KChIP3 drive the elevated bAP-associated Ca(2+) transients in distal apical dendrites. Alcohol-induced enhancement of bAPs may affect metaplasticity and signal integration in apical dendrites of hippocampal neurons leading to alterations in hippocampal function.

Chronic myelogenous leukemia (CML)

MedlinePlus

CML; Chronic myeloid leukemia; CGL; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

Chronic ethanol exposure enhances the aggressiveness of breast cancer: the role of p38γ

PubMed Central

Xu, Mei; Wang, Siying; Ren, Zhenhua; Frank, Jacqueline A.; Yang, Xiuwei H.; Zhang, Zhuo; Ke, Zun-ji; Shi, Xianglin; Luo, Jia

2016-01-01

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the scattering of MCF7, BT20 and T47D cell colonies in a 3-dimension culture system. Chronic ethanol exposure also increased colony formation in an anchorage-independent condition and stimulated cell invasion/migration. Chronic ethanol exposure increased cancer stem-like cell (CSC) population by more than 20 folds. Breast cancer cells exposed to ethanol in vitro displayed a much higher growth rate and metastasis in mice. Ethanol selectively activated p38γ MAPK and RhoC but not p38α/β in a concentration-dependent manner. SP-MCF7 cells, a derivative of MCF7 cells which compose mainly CSC expressed high levels of phosphorylated p38γ MAPK. Knocking-down p38γ MAPK blocked ethanol-induced RhoC activation, cell scattering, invasion/migration and ethanol-increased CSC population. Furthermore, knocking-down p38γ MAPK mitigated ethanol-induced tumor growth and metastasis in mice. These results suggest that chronic ethanol exposure can enhance the aggressiveness of breast cancer by activating p38γ MAPK/RhoC pathway. PMID:26655092

THE POTENTIAL EFFECT OF AMBIENT ARSENIC IN DRINKING WATER ON ODOR IDENTIFICATION IN AN AGRICULTURAL SAMPLE IN INNER MONGOLIA

EPA Science Inventory

There is some evidence that chronic exposure to arsenic (As) can have neuropathic and neurosensory effects in humans. It is unknown if As exposure affects the sense of smell. To determine if the ability to identify odors is impaired by chronic As exposure via drinking water, 15...

GENE EXPRESSION PROFILING OF MOUSE SKIN AND PAPILLOMAS FOLLOWING CHRONIC EXPOSURE TO MONOMETHYLARSONOUS ACID IN K6/ODC TRANSGENIC MICE

EPA Science Inventory

Methylarsonous acid [MMA(III)], a common metabolite of inorganic arsenic metabolism, increases tumor frequency in the skin of K6/ODC transgenic mice following a chronic exposure. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcin...

Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia.

PubMed

Zhu, Gaochun; Chen, Zhenying; Dai, Bo; Zheng, Chaoran; Jiang, Huaide; Xu, Yurong; Sheng, Xuan; Guo, Jingjing; Dan, Yu; Liang, Shangdong; Li, Guilin

2018-06-01

Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG). Rats were given lead acetate through drinking water freely at doses of 0 g/L (control group), 0.5 g/L (low lead group), and 2 g/L (high lead group) for 1 year. Our results demonstrated that lead exposure caused autonomic nervous dysfunction, including blood pressure and heart rate increased and heart rate variability (HRV) decreased. Western blotting results indicated that after lead exposure, the protein expression levels in the SG of P2X4 receptor, IL-1β and Cx43 were up-regulated, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was activated. Real-time PCR results showed that the mRNA expression of P2X4 receptor in the SG was higher in lead exposure group than that in the control group. Double-labeled immunofluorescence results showed that P2X4 receptor was co-expressed with glutamine synthetase (GS), the marker of satellite glial cells (SGCs). These changes were positively correlated with the dose of lead exposure. The up-regulated expression of P2X4 receptor in SGCs of the SG maybe enhance the sympathoexcitatory response induced by chronic lead exposure. © 2018 Wiley Periodicals, Inc.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures.

PubMed

Kunz, James L; Ingersoll, Chris G; Smalling, Kelly L; Elskus, Adria A; Kuivila, Kathryn M

2017-09-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubia and L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. azteca reproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;36:2308-2315. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 SETAC.

Association between chronic arsenic exposure and nutritional status among the women of child bearing age: a case-control study in Bangladesh.

PubMed

Milton, Abul H; Shahidullah, S M; Smith, Wayne; Hossain, Kazi S; Hasan, Ziaul; Ahmed, Kazi T

2010-07-01

The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 microg/L) through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any) of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI < 18.5) and 360 controls (BMI 18.5-24.99) were recruited from a baseline survey conducted among 2,341 women. An excess risk for malnutrition was observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for potential confounders such as participant's age, religion, education, monthly household income and history of oral contraceptive pills. Women exposed to arsenic >50 microg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1-3.6) increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20-45 years.

Oral exposure to polystyrene nanoparticles affects iron absorption

NASA Astrophysics Data System (ADS)

Mahler, Gretchen J.; Esch, Mandy B.; Tako, Elad; Southard, Teresa L.; Archer, Shivaun D.; Glahn, Raymond P.; Shuler, Michael L.

2012-04-01

The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron transport in an in vitro model of the intestinal epithelium and an in vivo chicken intestinal loop model. Intestinal cells that are exposed to high doses of nanoparticles showed increased iron transport due to nanoparticle disruption of the cell membrane. Chickens acutely exposed to carboxylated particles (50 nm in diameter) had a lower iron absorption than unexposed or chronically exposed birds. Chronic exposure caused remodelling of the intestinal villi, which increased the surface area available for iron absorption. The agreement between the in vitro and in vivo results suggests that our in vitro intestinal epithelium model is potentially useful for toxicology studies.

Does war hurt? Effects of media exposure after missile attacks on chronic pain.

PubMed

Lerman, Sheera F; Rudich, Zvia; Shahar, Golan

2013-03-01

This study focused on the effects of exposure to terrorist missile attacks on the physical and mental well being of chronic pain patients. In this prospective and longitudinal design, 55 chronic pain patients treated at a specialty pain clinic completed self-report questionnaires regarding their pain, depression and anxiety pre- and post a three week missile attack on the southern region of Israel. In addition, levels of direct and indirect exposure to the attacks were measured. Results of regression analyses showed that exposure to the attacks through the media predicted an increase in pain intensity and in the sensory component of pain during the pre-post war period, but did not predict depression, anxiety or the affective component of pain. These findings contribute to the understanding of the effects of terrorism on physical and emotional distress and identify chronic pain patients as a vulnerable population requiring special attention during terrorism-related stress.

A case-control study of chronic neuropsychiatric disease and organic solvent exposure in automobile assembly plant workers.

PubMed Central

Nelson, N A; Robins, T G; White, R F; Garrison, R P

1994-01-01

A case-control study of chronic neurological and psychiatric disease and occupational exposure to solvents was carried out in eight automobile assembly plants. Cases included 299 subjects who were granted medical disability retirement in 1980-8. Two control groups were selected, the first from those granted retirement in the same period because of medical disability from causes unrelated to solvent exposure. The second included hourly employees from the plant population. In these facilities, solvent exposures tended to be short term and low level, although common: the average duration of exposure was 2.3 years; about 41% experienced at least one day of exposure. Of those exposed, 46% had less than one year of exposure. Results for all psychiatric disease combined (273 cases) suggested that cases had lower exposures than either control group, regardless of how exposure was expressed. Results could not be explained by conventional confounding exposures or characteristics or by usual manifestations of the healthy worker effect. By contrast, chronic neurological disease, and multiple sclerosis in particular, seemed to be associated with exposure, although few cases were identified and observed increases in risk were not statistically significant. PMID:8199679

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure.

PubMed

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-07-02

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N=33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 μg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL×sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chronic Exposure to Ambient Ozone and Asthma Hospital Admissions among Children

PubMed Central

Lin, Shao; Liu, Xiu; Le, Linh H.; Hwang, Syni-An

2008-01-01

Background The association between chronic exposure to air pollution and adverse health outcomes has not been well studied. Objective This project investigated the impact of chronic exposure to high ozone levels on childhood asthma admissions in New York State. Methods We followed a birth cohort born in New York State during 1995–1999 to first asthma admission or until 31 December 2000. We identified births and asthma admissions through the New York State Integrated Child Health Information System and linked these data with ambient ozone data (8-hr maximum) from the New York State Department of Environmental Conservation. We defined chronic ozone exposure using three indicators: mean concentration during the follow-up period, mean concentration during the ozone season, and proportion of follow-up days with ozone levels > 70 ppb. We performed logistic regression analysis to adjust for child’s age, sex, birth weight, and gestational age; maternal race/ethnicity, age, education, insurance status, smoking during pregnancy, and poverty level; and geographic region, temperature, and copollutants. Results Asthma admissions were significantly associated with increased ozone levels for all chronic exposure indicators (odds ratios, 1.16–1.68), with a positive dose–response relationship. We found stronger associations among younger children, low sociodemographic groups, and New York City residents as effect modifiers. Conclusion Chronic exposure to ambient ozone may increase the risk of asthma admissions among children. Younger children and those in low socioeconomic groups have a greater risk of asthma than do other children at the same ozone level. PMID:19079727

Exposure to cold and draught, alcohol consumption, and the NS-phenotype are associated with chronic bronchitis: an epidemiological investigation of 3387 men aged 53-75 years: the Copenhagen Male Study

PubMed Central

Suadicani, P; Hein, H; Meyer, H; Gyntelberg, F

2001-01-01

OBJECTIVES—This study was performed to estimate the strength of association between chronic bronchitis and lifetime exposure to occupational factors, current lifestyle, and the NS-phenotype in the MNS blood group among middle aged and elderly men.
METHODS—The study was carried out within the frameworks of the Copenhagen Male Study. Of 3387 men 3331 men with a mean age of 63 (range 53-75) years could be classified by prevalence of chronic bronchitis. As well as the completion of a large questionnaire on health, lifestyle, and working conditions, all participants had a thorough examination, including measurements of height and weight and blood pressure and a venous blood sample was taken for the measurement of serum cotinine and MNS typing; 16.5% of the men had the NS-phenotype. Chronic bronchitis was defined as cough and phlegm lasting 3 months or more for at least 2 years; 14.6% had chronic bronchitis.
RESULTS—Smoking and smoke inhalation were the factors most strongly associated with prevalence of chronic bronchitis. There were three major new findings: (a) long term (>5 years) occupational exposure to cold and draught was associated with a significantly increased prevalence of chronic bronchitis; compared with others, and adjusted for confounders, the odds ratio (OR) with 95% confidence interval (95% CI) was 1.4 (1.1 to 1.7), p=0.004; (b) a significant J shaped association existed between alcohol use and bronchitis, p<0.001, with the lowest prevalence found among moderate users; (c) a significant gene by environment association existed between smoking and the NS-phenotype in the MNS blood group; only among smokers was the NS-phenotype associated with a significantly decreased risk of chronic bronchitis, OR 0.67 (0.47-0.97), p=0.02. Other well known associations between dust, fumes, and even exposure to solvents and bronchitis were confirmed.
CONCLUSION—The results emphasise the multifactorial nature of chronic bronchitis, and show some hitherto unrecognised associations between cold and draught exposure, alcohol consumption, and the NS-phenotype and chronic bronchitis.


Keywords: alcohol; chronic bronchitis; cold; draught; genetic marker; MNS; occupational exposure PMID:11171928

Bumblebee learning and memory is impaired by chronic exposure to a neonicotinoid pesticide

PubMed Central

Stanley, Dara A.; Smith, Karen E.; Raine, Nigel E.

2015-01-01

Bumblebees are exposed to pesticides applied for crop protection while foraging on treated plants, with increasing evidence suggesting that this sublethal exposure has implications for pollinator declines. The challenges of navigating and learning to manipulate many different flowers underline the critical role learning plays for the foraging success and survival of bees. We assessed the impacts of both acute and chronic exposure to field-realistic levels of a widely applied neonicotinoid insecticide, thiamethoxam, on bumblebee odour learning and memory. Although bees exposed to acute doses showed conditioned responses less frequently than controls, we found no difference in the number of individuals able to learn at field-realistic exposure levels. However, following chronic pesticide exposure, bees exposed to field-realistic levels learnt more slowly and their short-term memory was significantly impaired following exposure to 2.4 ppb pesticide. These results indicate that field-realistic pesticide exposure can have appreciable impacts on learning and memory, with potential implications for essential individual behaviour and colony fitness. PMID:26568480

Central nervous system effect of chronic exposure to organophosphate insecticides.

DOT National Transportation Integrated Search

1963-10-01

Two cases are reported in which persistent CNS changes were noted in aerial applicator pilots after chronic exposure to organophosphate insecticides. The synptomatology, the basis for these symptoms and EEG changes and their reversibility are discuss...

Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites

PubMed Central

Veeramachaneni, D. N. Rao; Walters, William A.; Lozupone, Catherine; Palmer, Jennifer; Hewage, M. K. Kurundu; Bhatnagar, Rohil; Amir, Amnon; Kennett, Mary J.; Knight, Rob

2017-01-01

ABSTRACT Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may contribute to chronic colonic and systemic inflammation. We hypothesized that perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring is due to alterations in the microbiome and colonic metabolome. The 16S rRNA amplicon sequencing analysis revealed differences in beta diversity with a significant reduction in the relative abundances of short-chain fatty acid (SCFA) producers such as Oscillospira and Ruminococcaceae due to BPA exposure. Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed alterations in global metabolism and amino acid metabolism. Thus, our findings indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to chronic colon and liver inflammation. IMPORTANCE Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability—three common early biomarkers of inflammation-promoted chronic diseases. In addition, we showed that SCFA ameliorated BPA-induced intestinal permeability in vitro. Thus, our study results suggest that correcting environmental toxicant-induced bacterial dysbiosis early in life may reduce the risk of chronic diseases later in life. PMID:29034330

A pilot study of the effect of human breast milk on urinary metabolome analysis in infants.

PubMed

Shoji, Hiromichi; Taka, Hikari; Kaga, Naoko; Ikeda, Naho; Kitamura, Tomohiro; Miura, Yoshiki; Shimizu, Toshiaki

2017-08-28

This study aimed to examine the nutritional effect of breast feeding on healthy term infants by using urinary metabolome analysis. Urine samples were collected from 19 and 14 infants at 1 and 6 months, respectively. Infants were separated into two groups: the breast-fed group receiving <540 mL/week of their intake from formula (n=13 at 1 month; n=9 at 6 months); and the formula-fed group receiving no breast milk (BM) (n=6 at 1 month; n=5 at 6 months). Urinary metabolome analysis was performed using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS). A total of 29 metabolites were detected by CE-TOF/MS metabolome analysis in all samples. Urinary excretion of choline metabolites (choline base solution, N,N-dimethylglycine, sarcosine, and betaine) at 1 month were significantly (p<0.05) higher in breast-fed infants than in formula-fed infants. However, choline metabolites were not significantly different between the groups at 6 months. Urinary excretion of lactic acid in breast-fed infants at 1 and 6 months was significantly lower than that in formula-fed infants. Urinary l(-)-threonine and l-carnosine excretion at 1 month was significantly lower in breast-fed infants than in formula-fed infants, but it was not significantly different between the groups at 6 months. The type of feeding in early infancy affects choline metabolism, as well as lactate, threonine, and carnosine levels, in healthy term infants. Urinary metabolome analysis by the CE-TOF/MS method is useful for assessing nutritional metabolism in infants.

A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients.

PubMed

Derosa, Giuseppe; D'Angelo, Angela; Romano, Davide; Maffioli, Pamela

2016-10-28

The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L -carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA 1c ), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA 1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L -carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients

PubMed Central

Derosa, Giuseppe; D’Angelo, Angela; Romano, Davide; Maffioli, Pamela

2016-01-01

The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers. PMID:27801825

Effect of Carnosine on Renal Function, Oxidation and Glycation Products in the Kidneys of High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

PubMed

Fatih Aydın, Abdurrahman; Küçükgergin, Canan; Bingül, İlknur; Doğan-Ekici, Işın; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

2017-05-01

High fat diet (HFD) and low dose of streptozotocin (STZ)-treated rats provide an animal model for type 2 Diabetes Mellitus (T2DM). Oxidative stress plays a role in the development of diabetic complications. Carnosine (CAR) has antioxidant and antiglycating properties. We investigated effects of CAR on renal function, oxidation and glycation products in HFD+STZ-rats. Rats were fed with HFD (60% of total calories from fat) for 4 weeks and then a single dose STZ (40 mg/kg; i.p.) was applied. Rats with blood glucose levels above 200 mg/dL were fed with HFD until the end of the 12 th week. CAR (250 mg/kg body weight; i.p.; 5 times a week) was administered to rats for the last 4 weeks. Glycated hemoglobin (HbA1c), glucose, lipids, and andrenal function tests in serum as well as reactive oxygen species, malondialdehyde, protein carbonyl, advanced oxidation protein products, advanced glycation end products (AGEs), antioxidant power, and antioxidant enzyme activities and their mRNA expressions in kidneys were determined. CAR treatment did not alter glucose and HbA1c, but it decreased serum lipids, creatinine, and urea levels in HFD+STZ rats. Oxidation products of lipids and proteins and AGEs levels decreased, but antioxidant enzyme activities and their mRNA expressions remained unchanged due to CAR treatment. Our results indicate that CAR treatment alleviated renal function and decreased accumulation of oxidation and glycation products in kidneys in HFD+STZ-rats. © Georg Thieme Verlag KG Stuttgart · New York.

Treatment of Chronic PTSD by Cognitive Therapy and Exposure: 5-Year Follow-up

ERIC Educational Resources Information Center

Tarrier, Nicholas; Sommerfield, Claire

2004-01-01

Patients who had taken part in a randomized clinical trial of the treatment of chronic PTSD by either cognitive therapy or imaginal exposure were reassessed after 5 years. At 5-year follow-up a clear superiority of cognitive therapy over imaginal exposure emerged, although there had been no difference between the two treatment groups up to 12…

Long-term respiratory health effects in textile workers.

PubMed

Lai, Peggy S; Christiani, David C

2013-03-01

Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed byssinosis. The purpose of this review is to evaluate the effect of long-term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications, such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Cessation of exposure to cotton dust leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage:dendritic cell population ratio as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton dust-related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Textile dust-related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers.

Long term respiratory health effects in textile workers

PubMed Central

Lai, Peggy S.; Christiani, David C.

2013-01-01

Purpose of review Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed Byssinosis. The purpose of this review is to evaluate the effect of long term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Recent findings Cessation of exposure to cotton dusts leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage:dendritic cell population as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton-dust related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Summary Textile dust related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers. PMID:23361196

mRNA Transcript Abundance during Plant Growth and the Influence of Li + Exposure

DOE PAGES

Duff, M. C.; Kuhne, W. W.; Halverson, N. V.; ...

2014-10-23

Lithium (Li) toxicity in plants is, at a minimum, a function of Li + concentration, exposure time, species and growth conditions. Most plant studies with Li + focus on short-term acute exposures. This study examines short- and long-term effects of Li + exposure in Arabidopsis with Li + uptake studies and measured shoot mRNA transcript abundance levels in treated and control plants. Stress, pathogen-response and arabinogalactan protein genes were typically more up-regulated in older (chronic, low level) Li +-treatment plants and in the much younger plants from acute high-level exposures. The gene regulation behavior of high-level Li + resembled priormore » studies due to its influence on: inositol synthesis, 1-aminocyclopropane-1-carboxylate synthases and membrane ion transport. In contrast, chronically-exposed plants had gene regulation responses that were indicative of pathogen, cold, and heavy-metal stress, cell wall degradation, ethylene production, signal transduction, and calcium-release modulation. Acute Li + exposure phenocopies magnesium-deficiency symptoms and is associated with elevated expression of stress response genes that could lead to consumption of metabolic and transcriptional energy reserves and the dedication of more resources to cell development. In contrast, chronic Li + exposure increases expression signal transduction genes. The identification of new Li +-sensitive genes and a gene-based “response plan” for acute and chronic Li + exposure are delineated.« less

Development of a Novel Simulation Reactor for Chronic Exposure to Atmospheric Particulate Matter

NASA Astrophysics Data System (ADS)

Ye, Jianhuai; Salehi, Sepehr; North, Michelle L.; Portelli, Anjelica M.; Chow, Chung-Wai; Chan, Arthur W. H.

2017-02-01

Epidemiological studies have shown that air pollution is associated with the morbidity and mortality from cardiopulmonary diseases. Currently, limited experimental models are available to evaluate the physiological and cellular pathways activated by chronic multi-pollutant exposures. This manuscript describes an atmospheric simulation reactor (ASR) that was developed to investigate the health effects of air pollutants by permitting controlled chronic in vivo exposure of mice to combined particulate and gaseous pollutants. BALB/c mice were exposed for 1 hr/day for 3 consecutive days to secondary organic aerosol (SOA, a common particulate air pollutant) at 10-150 μg/m3, SOA (30 μg/m3) + ozone (65 ppb) or SOA + ozone (65 ppb) + nitrogen dioxide (NO2; 100 ppb). Daily exposure to SOA alone led to increased airway hyperresponsiveness (AHR) to methacholine with increasing SOA concentrations. Multi-pollutant exposure with ozone and/or NO2 in conjunction with a sub-toxic concentration of SOA resulted in additive effects on AHR to methacholine. Inflammatory cell recruitment to the airways was not observed in any of the exposure conditions. The ASR developed in this study allows us to evaluate the chronic health effects of relevant multi-pollutant exposures at ‘real-life’ levels under controlled conditions and permits repeated-exposure studies.

mRNA Transcript abundance during plant growth and the influence of Li(+) exposure.

PubMed

Duff, M C; Kuhne, W W; Halverson, N V; Chang, C-S; Kitamura, E; Hawthorn, L; Martinez, N E; Stafford, C; Milliken, C E; Caldwell, E F; Stieve-Caldwell, E

2014-12-01

Lithium (Li) toxicity in plants is, at a minimum, a function of Li(+) concentration, exposure time, species and growth conditions. Most plant studies with Li(+) focus on short-term acute exposures. This study examines short- and long-term effects of Li(+) exposure in Arabidopsis with Li(+) uptake studies and measured shoot mRNA transcript abundance levels in treated and control plants. Stress, pathogen-response and arabinogalactan protein genes were typically more up-regulated in older (chronic, low level) Li(+)-treatment plants and in the much younger plants from acute high-level exposures. The gene regulation behavior of high-level Li(+) resembled prior studies due to its influence on: inositol synthesis, 1-aminocyclopropane-1-carboxylate synthases and membrane ion transport. In contrast, chronically-exposed plants had gene regulation responses that were indicative of pathogen, cold, and heavy-metal stress, cell wall degradation, ethylene production, signal transduction, and calcium-release modulation. Acute Li(+) exposure phenocopies magnesium-deficiency symptoms and is associated with elevated expression of stress response genes that could lead to consumption of metabolic and transcriptional energy reserves and the dedication of more resources to cell development. In contrast, chronic Li(+) exposure increases expression signal transduction genes. The identification of new Li(+)-sensitive genes and a gene-based "response plan" for acute and chronic Li(+) exposure are delineated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of stress on alcohol drinking: a review of animal studies

PubMed Central

Lopez, Marcelo F.; Doremus-Fitzwater, Tamara L.

2011-01-01

Rationale While stress is often proposed to play a significant role in influencing alcohol consumption, the relationship between stress and alcohol is complex and poorly understood. Over several decades, stress effects on alcohol drinking have been studied using a variety of animal models and experimental procedures, yet this large body of literature has generally produced equivocal results. Objectives This paper reviews results from animal studies in which alcohol consumption is evaluated under conditions of acute/sub-chronic stress exposure or models of chronic stress exposure. Evidence also is presented indicating that chronic intermittent alcohol exposure serves as a stressor that consequently influences drinking. Results The effects of various acute/sub-chronic stress procedures on alcohol consumption have generally been mixed, but most study outcomes suggest either no effect or decreased alcohol consumption. In contrast, most studies indicate that chronic stress, especially when administered early in development, results in elevated drinking later in adulthood. Chronic alcohol exposure constitutes a potent stressor itself, and models of chronic intermittent alcohol exposure reliably produce escalation of voluntary alcohol consumption. Conclusions A complex and dynamic interplay among a wide array of genetic, biological, and environmental factors govern stress responses, regulation of alcohol drinking, and the circumstances in which stress modulates alcohol consumption. Suggestions for future directions and new approaches are presented that may aid in developing more sensitive and valid animal models that not only better mimic the clinical situation, but also provide greater understanding of mechanisms that underlie the complexity of stress effects on alcohol drinking. PMID:21850445

Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.

PubMed

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.

Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

PubMed Central

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence. PMID:23300696

Unexplained dyspnea in a patient of chronic arsenicosis: A diagnostic challenge and learning curve for physicians

PubMed Central

Sengupta, Amitabha; Maji, Arnab; Jash, Debraj; Maikap, Malay

2015-01-01

Chronic arsenic exposure causes cutaneous effects like hyperkeratosis, peripheral vascular disease, hypertension, ischemic heart disease, non-cirrhotic portal hypertension, hepatomegaly, peripheral neuropathy, respiratory involvement, bad obstetrical outcome, hematological disturbances, and diabetes mellitus. Here we present a case of a 24-year-old lady, with chronic exposure to arsenic, presenting to us with progressive dyspnea. We found pulmonary arterial hypertension (PAH) as a cause of her dyspnea. PAH can occur in arsenicosis, secondary to arsenic-induced chronic obstructive pulmonary disease (COPD), lung fibrosis, and portal hypertension, which we excluded by appropriate investigations in our case. We also excluded a familial or heritable form of PAH. Thus, with the exclusion of all these secondary causes of PAH, as well as a hereditary cause, we came to a conclusion that this PAH might be due to chronic arsenic exposure. To the best of our knowledge, no case of PAH in chronic arsenicosis has been reported to date. PMID:25814805

Chronic bronchitis, work related respiratory symptoms, and pulmonary function in welders in New Zealand.

PubMed

Bradshaw, L M; Fishwick, D; Slater, T; Pearce, N

1998-03-01

A cross sectional study of respiratory symptoms and lung function in welders was performed at eight New Zealand welding sites: 62 current welders and 75 non-welders participated. A questionnaire was administered to record demographic data, smoking habit, and current respiratory symptoms. Current and previous welding exposures were recorded to calculate a total lifetime welding fume exposure index. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) were measured before the start of the shift. There were no significant differences in ethnicity, smoking habits, or years of work experience between welders and non-welders. Symptoms of chronic bronchitis were more common in current welders (11.3%) than in non-welders (5.0%). Of those workers with a cumulative exposure index to welding fume > or = 10 years, 16.7% reported symptoms of chronic bronchitis compared with 4.7% of those with a cumulative exposure index < 4 years (odds ratio (OR) 4.1, 95% confidence interval (95% CI) 0.90 to 17.6). Workers with chronic bronchitis had significantly lower measures of baseline PEF (p = 0.008) and FEV/FVC ratio (p = 0.001) than workers without chronic bronchitis. Multivariate analysis showed that current smoking (OR 9.3, 1.0 to 86.9) and total exposure index to welding fumes > 10 years (OR 9.5, 1.3 to 71.9) were independent risk factors for chronic bronchitis. The report of any work related respiratory symptom was more prevalent in welders (30.7%) than non-welders (15.0%) and workers with these symptoms had significantly lower FEV, (p = 0.004) and FVC (p = 0.04) values. Multivariate analysis identified a high proportion of time spent welding in confined spaces as the main risk factor for reporting these symptoms (OR 2.8, 1.0 to 8.3). This study has documented a high prevalence of symptoms of chronic bronchitis and other work related respiratory symptoms in current welders. Also, workers with chronic bronchitis had reduced PEF and FEV/FVC compared with those without chronic bronchitis. These symptoms related both to cigarette smoking and a measure of lifetime exposure to welding fume.

Toxic exposure to ethylene dibromide and mercuric chloride: effects on laboratory-reared octopuses.

PubMed

Adams, P M; Hanlon, R T; Forsythe, J W

1988-01-01

The effects of acute and chronic exposure to either ethylene dibromide (EDB) or mercuric chloride (MC) were studied in laboratory-reared Octopus joubini, O. maya and O. bimaculoides. The advantages of using octopuses were that the responses were immediate, highly visible and sensitive. All species demonstrated signs of toxicity to acute and chronic exposure to EDB and to MC. A dosage-sensitive relationship for the loss and subsequent recovery of locomotor response and of chromatophore expansion was found for each species after acute exposure. For each species the LC50 for chronic exposure occurred within 12 hr at 100 mg/l for EDB and within 3 hr at 1,000 mg/l for MC. This study demonstrated the potential usefulness of laboratory-reared octopuses in evaluating the toxicity of marine environmental pollutants.

Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mostafalou, Sara; Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca

Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies,more » autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. - Highlights: ► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up.« less

Behavioral and Immunohistochemical Study of the Effects of Subchronic and Chronic Exposure to Glyphosate in Mice

PubMed Central

Ait Bali, Yassine; Ba-Mhamed, Saadia; Bennis, Mohamed

2017-01-01

Many epidemiological studies have described an adolescent-related psychiatric illness and sensorimotor deficits after Glyphosate based herbicide (GBH) exposure. GBH exposure in animal models of various ages suggests that it may be neurotoxic and could impact brain development and subsequently, behavior in adulthood. However, its neurotoxic effects on adolescent brain remain unclear and the results are limited. The present study was conducted to evaluate the neurobehavioral effects of GBH following acute, subchronic (6 weeks) and chronic (12 weeks) exposure (250 or 500 mg/kg/day) in mice treated from juvenile age until adulthood. Mice were subjected to behavioral testing with the open field (OF), the elevated plus maze, the tail suspension and Splash tests (STs). Their behaviors related to exploratory activity, anxiety and depression-like were recorded. After completion of the behavioral testing, adult mice were sacrificed and the expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and serotonin (5-HT) in the dorsal raphe nucleus (DRN), the basolateral amygdala (BLA) and the ventral medial prefrontal cortex (mPFC) was evaluated using immunohistochemical procedure. Our results indicate that unlike acute exposure, both subchronic and chronic exposure to GBH induced a decrease in body weight gain and locomotor activity, and an increase of anxiety and depression-like behavior levels. In addition, the immunohistochemical findings showed that only the chronic treatment induced a reduction of TH-immunoreactivity. However, both subchronic and chronic exposure produced a reduction of 5-HT-immunoreactivity in the DRN, BLA and ventral mPFC. Taken together, our data suggest that exposure to GBH from juvenile age through adulthood in mice leads to neurobehavioral changes that stem from the impairment of neuronal developmental processes. PMID:28848410

Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium

PubMed Central

Cartularo, Laura; Laulicht, Freda; Sun, Hong; Kluz, Thomas; Freedman, Jonathan H.; Costa, Max

2015-01-01

Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the earth’s crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24 hours; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181 genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, and cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24 hours indicated a reduction in global levels of histone methylation and acetylation that persisted 72 hours post-treatment. PMID:26314618

Evidence for a causative role of N-methyl-D-aspartate receptors in an in vitro model of alcohol withdrawal hyperexcitability.

PubMed

Thomas, M P; Monaghan, D T; Morrisett, R A

1998-10-01

Synaptic mechanisms underlying hyperexcitability due to withdrawal from chronic ethanol exposure were investigated in a hippocampal explant model system using electrophysiological techniques. Whole-cell voltage clamp recordings from CA1 pyramidal cells demonstrated that acute ethanol exposure inhibited N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents by over 40%. Chronic ethanol exposure for 6 to 11 days at 35 or 75 mM induced no differences from control explants in the fast component of the population synaptic response (non-NMDAR-mediated). Prolonged field potential recordings (to 10 hr) were used to monitor the withdrawal process in vitro. Ethanol-exposed explants from both 35 and 75 mM groups displayed an increase (60% and 89%, respectively) in the NMDAR-mediated component of synaptic transmission on withdrawal from chronic exposure. Prolonged tonic-clonic electrographic seizure activity was consistently observed after ethanol withdrawal only after the increase in NMDAR function. This hyperexcitability was inhibited by the NMDAR antagonist D-2-amino-5-phosphonovaleric acid and returned once the NMDAR component was reestablished after antagonist washout. In situ hybridization studies suggest that expression of NR2B subunit mRNA may be enhanced in explants after chronic ethanol exposure. No lasting differences were observed in the NMDAR component after acute in vitro ethanol exposure and withdrawal. These data suggest that the occurance of ethanol withdrawal hyperexcitability in this system may be directly dependent on alterations in NMDAR function after chronic exposure. Since this region and others that contain ethanol sensitive NMDARs may serve as epileptic foci, long term alterations in NMDAR function may be expected to generate paroxysmal depolarizing shifts underlying ictal events after withdrawal from ethanol exposure.

Quantitative risk assessment for a glass fiber insulation product.

PubMed

Fayerweather, W E; Bender, J R; Hadley, J G; Eastes, W

1997-04-01

California Proposition 65 (Prop65) provides a mechanism by which the manufacturer may perform a quantitative risk assessment to be used in determining the need for cancer warning labels. This paper presents a risk assessment under this regulation for professional and do-it-yourself insulation installers. It determines the level of insulation glass fiber exposure (specifically Owens Corning's R-25 PinkPlus with Miraflex) that, assuming a working lifetime exposure, poses no significant cancer risk under Prop65's regulations. "No significant risk" is defined under Prop65 as a lifetime risk of no more than one additional cancer case per 100,000 exposed persons, and nonsignificant exposure is defined as a working lifetime exposure associated with "no significant risk." This determination can be carried out despite the fact that the relevant underlying studies (i.e., chronic inhalation bioassays) of comparable glass wool fibers do not show tumorigenic activity. Nonsignificant exposures are estimated from (1) the most recent RCC chronic inhalation bioassay of nondurable fiberglass in rats; (2) intraperitoneal fiberglass injection studies in rats; (3) a distributional, decision analysis approach applied to four chronic inhalation rat bioassays of conventional fiberglass; (4) an extrapolation from the RCC chronic rat inhalation bioassay of durable refractory ceramic fibers; and (5) an extrapolation from the IOM chronic rat inhalation bioassay of durable E glass microfibers. When the EPA linear nonthreshold model is used, central estimates of nonsignificant exposure range from 0.36 fibers/cc (for the RCC chronic inhalation bioassay of fiberglass) through 21 fibers/cc (for the i.p. fiberglass injection studies). Lower 95% confidence bounds on these estimates vary from 0.17 fibers/cc through 13 fibers/cc. Estimates derived from the distributional approach or from applying the EPA linear nonthreshold model to chronic bioassays of durable fibers such as refractory ceramic fiber or E glass microfibers are intermediate to the other approaches. Estimates based on the Weibull 1.5-hit nonthreshold and 2-hit threshold models exceed by at least a factor of 10 the corresponding EPA linear nonthreshold estimates. The lowest nonsignificant exposures derived in this assessment are at least a factor of two higher than field exposures measured for professionals installing the R-25 fiberglass insulation product and are orders of magnitude higher than the estimated lifetime exposures for do-it-yourselfers.

Occupation and chronic obstructive pulmonary disease (COPD).

PubMed

Cullinan, Paul

2012-01-01

There is growing interest in preventable, non-smoking causes of chronic obstructive pulmonary disease (COPD), among which are chronic exposures to respiratory irritants in the workplace. Reviews of occupational COPD in specific occupations and industries and in general populations; supplemented with other or more recently published material. There is good evidence for an increased risk of COPD from certain specific exposures (coal mine dust, silica, welding fume, textile dust, agricultural dust, cadmium fume). Less clear is the causal role of non-specific dusts or fumes/gases in general populations where the available literature is notably uncritical. Other specific exposures, such as diesel fume; interactions between specific exposures and cigarette smoking; the development of safe working limits. Occupations with large numbers of exposed employees, particularly in low-income countries.

Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.

PubMed

Mathur, Priya; Guo, Su

2011-06-01

Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.

PubMed

Dina, Olayinka A; Joseph, Elizabeth K; Levine, Jon D; Green, Paul G

2010-04-01

While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. Copyright 2010 American Pain Society. All rights reserved.

Incidence of chronic bronchitis in a cohort of pulp mill workers with repeated gassings to sulphur dioxide and other irritant gases

PubMed Central

2013-01-01

Background Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. Methods The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970–2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. Results The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). Conclusions Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment. PMID:24354705

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

PubMed Central

Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

2015-01-01

The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

Chronic occupational stress exposure may increase the vulnerability to acoustic trauma in military professionals.

PubMed

Mălina, Ciumaşu-Rimbu

2015-01-01

Today little is known about the connection between chronic stress exposure and hearing loss. These effects cannot be explained by differences in HPA axis response but recent studies saying that chronic stress induced limbic system alterations spread to nonlimbic areas affecting auditory system might be the key. On the other hand we know that subjects exposed to chronic stress may prove hypersensitivity to novel stressors. The aim of this study is to confirm that occupational chronic stress (OCS) exposure determines vulnerability to acoustic trauma and to establish a method to identify individuals at risk prior to their exposure to high intensity acoustic stimulus. 60 military personnel with known acoustic trauma injury evidentiated through audiograms and occupational chronic stress exposure quantified through validated questionnaires were exposed to mild novel stressor: occupational medicine evaluation and clinically assessed for maladaptive cardiovascular response (MCVR). Employees were split in two groups, group 1 (MCVR) and group 2 (non MCVR). We found positive correlation between level of perceived OCS and level of hearing loss on entire group and between groups with values of parameters significantly higher in group 1. Subjects exposed to OCS with hypersensitivity to novel stressor evidentiated through maladaptive cardiovascular stress response may be more vulnerable to high intensity acoustic stimulus and consequently acoustic trauma. Establishing methods and biomarkers that help us indentify individuals at risk of developing acoustic trauma might decrease the high burden of hearing loss.

Comparison of the effects of acute and chronic psychological stress on metabolic features in rats*

PubMed Central

Rostamkhani, Fatemeh; Zardooz, Homeira; Zahediasl, Saleh; Farrokhi, Babak

2012-01-01

This study was aimed to compare the effects of acute and chronic psychological stress on metabolic factors. Forty-two male Wistar rats were divided into control and stressed groups. Stress was applied by a communication box acutely (1 d) and chronically (15 and 30 d). Blood sampling was carried out by retro-orbital-puncture method. The plasma levels of glucose, cholesterol, triglyceride, insulin, and corticosterone were measured. In addition, feed and water intake, latency to eat and drink, adrenal and body weights were determined. Acute and chronic psychological stress did not significantly change basal plasma corticosterone levels. However, immediately (1 min) after acute exposure to stress, plasma corticosterone level increased compared to that before stress exposure. Acute stress increased plasma insulin levels significantly. Fifteen days of stress exposure resulted in plasma glucose increase. Chronic stress significantly increased feed intake, latency to eat, and adrenal weight compared to acute stress. The body weights of both control and stressed groups increased markedly during the experiment. Homeostasis model assessment of insulin resistance (HOMA-IR) index did not change significantly in the stressed group. In conclusion, application of acute and chronic psychological stress leads to different metabolic and/or behavioral changes but the metabolic changes resulting from acute exposure to stress seem to be more pronounced. PMID:23125083

Stress response in rat brain after different durations of noise exposure.

PubMed

Samson, James; Sheeladevi, Rathinasamy; Ravindran, Rajan; Senthilvelan, Manohar

2007-01-01

The alteration in the levels of plasma corticosterone, brain norepinephrine (NE), and expression of brain heat shock proteins (Hsp70) after different durations of noise exposure (acute, 1 day; sub-acute, 15 days; chronic, 30 days) has been studied to analyze their role in combating time-dependent stress effects of noise. Broadband white noise (100dB) exposure to male Wistar albino rats significantly increased the levels of plasma corticosterone and NE in all three durations of noise exposure. The sustained increase observed in their levels in the chronic group suggests that animals are not getting adapted to noise even after 30 days of exposure. The important role of Hsp70 in combating noise induced stress is evident from the significant increase in its expression after chronic exposure, while there was a reciprocal decrease in the NE and corticosterone when compared with their levels after acute and sub-acute noise exposure. This clearly indicates that the time-dependent stress response to noise exposure is a complex mechanism involving highly interconnected systems such as hypothalamo-pituitary-adrenal (HPA) axis, heat shock proteins and may have serious implications in vital organs, particularly in the brain when there is a prolonged noise exposure.

Chronic bronchitis in farmers.

PubMed

Melbostad, E; Eduard, W; Magnus, P

1997-08-01

Chronic bronchitis was studied in relation to work time and years of exposure in farming, as well as to production type, dusty occupation outside farming, and the combination of work exposure and smoking, in a population of farmers. In 1989 a representative cohort of 10,792 farmers and spouses was selected from a government register and invited to participate in a cross-sectional study in 1991. The total response rate was 80%. There were 33% part-time farmers, and among the men 32% of the full-time and 42% of the part-time farmers had worked in dusty occupations outside farming. Bronchitis symptoms were recorded on a self-administered questionnaire, spirometric data were obtained, and internal reference equations were calculated for forced expiratory volume in 1 s (FEV1.0). The exposure factors of importance for chronic bronchitis were full-time farming versus part-time farming, livestock production types (poultry, dairy, swine, horse and combinations), and occupational dust exposure outside agriculture. The combinations of the work exposure factors were significant and showed a 2- to 3-fold increase in risk for chronic bronchitis. Combinations with smoking showed up to a 6-fold increase in risk. Over the age of 50 years, chronic bronchitis was a risk factor for airway obstruction defined as the standardized residuals for FEV1.0 less than -2 for both nonsmokers (OR 2.8, 95% CI 1.1-6.8) and smokers (OR 8.5, 95% CI 5.1-14.3). Work exposure factors in farming and other dusty occupations enhance the risk for chronic bronchitis from 2- to 3-fold for farmers. In combination with smoking the risk increases to up to 6-fold.

The mechanisms for lung cancer risk of PM2.5 : Induction of epithelial-mesenchymal transition and cancer stem cell properties in human non-small cell lung cancer cells.

PubMed

Wei, Hongying; Liang, Fan; Cheng, Wei; Zhou, Ren; Wu, Xiaomeng; Feng, Yan; Wang, Yan

2017-11-01

Fine particulate matter (PM 2.5 ) is a major component of air pollutions that are closely associated with increased risk of lung cancer. However, the role of PM 2.5 in the etiology of lung cancer is largely unknown. In this study, we performed acute (24 hours) and chronic (five passages) exposure models to investigate the carcinogenetic mechanisms of PM 2.5 by targeting the induction of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties in human non-small cell lung cancer cell line A549. We found that both acute and chronic PM 2.5 exposure enhanced cell migration and invasion, decreased mRNA expression of epithelial markers and increased mRNA expression of mesenchymal markers. Chronic PM 2.5 exposure further induced notable EMT morphology and CSC properties, indicating the developing process of cell malignant behaviors from acute to chronic PM 2.5 exposure. CSC properties induced by chronic PM 2.5 exposure characterized with increased cell-surface markers (CD44, ABCG2), self-renewal genes (SOX2 and OCT4), side population cells and neoplastic capacity. Furthermore, the levels of three stemness-associated microRNAs, Let-7a, miR-16 and miR-34a, were found to be significantly downregulated by chronic PM 2.5 exposure, with microarray data analysis from TCGA database showing their lower expression in human lung adenocarcinoma tissues than that in the adjacent normal lung tissues. These data revealed that the induction of EMT and CSC properties were involved in the lung cancer risk of PM 2.5 , and implicated CSC properties and related microRNAs as possible biomarkers for carcinogenicity prediction of PM 2.5 . © 2017 Wiley Periodicals, Inc.

A dose for the wiser is enough: the alcohol benefits for associative learning in zebrafish.

PubMed

Chacon, Diana M; Luchiari, Ana C

2014-08-04

This study aimed to test seeking behavior caused by alcohol and the drug effects on learning in the zebrafish, Danio rerio. Three treatments were conducted: acute, chronic and withdrawal, using 0.10%, 0.25%, and 1.00% alcohol and control (0.00%) (vol/vol.%). For the drug seeking behavior, we used a place preference paradigm (shuttle box tank) before and after alcohol exposure in acute (single exposure) and chronic (7 days) treatments. We observed a change in the basal preference due to the association with alcohol only for 0.25% and 1.00% doses in both acute and chronic offering, indicating an alcohol-seeking behavior after the drug exposure. For the learning task, two treatments were tested: chronic alcohol exposure (26 days including the learning period) and alcohol withdrawal (15 days of alcohol exposure before the learning period). During the learning period, fish received light stimulus followed by food in a pre-defined area of the tank for 8 consecutive days. The low dose group (0.10%) learned the task by the 3rd day both in chronic and withdrawal treatments. The higher doses (0.25% and 1.00%) caused a learning impairment in the chronic treatment group, while fish from the alcohol withdrawal treatment displayed learning on the final testing day. Therefore, we suggest that high alcohol doses impair learning and cause drug seeking behavior, even after drug exposure cessation, while low doses positively affect learning and do not cause seeking behavior. Given our results we propose that the zebrafish is a promising model for identifying active compounds, antibodies or genes which modulate the alcohol dual effects: learning improvement and reinforcing behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Lack of association between chronic exposure to biomass fuel smoke and markers of right ventricular pressure overload at high altitude

PubMed Central

Caravedo, Maria A.; Painschab, Matthew S.; Davila-Roman, Victor G.; De Ferrari, Aldo; Gilman, Robert H.; Vasquez-Villar, Angel D.; Pollard, Suzanne L.; Miranda, J. Jaime; Checkley, William

2014-01-01

Background Chronic exposure to biomass fuel smoke has been implicated in the development of pulmonary hypertension and right ventricular pressure/volume overload through activation of inflammation, increase in vascular resistance and endothelial dysfunction. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and echocardiography-derived pulmonary artery systolic pressure (PASP) levels in a high-altitude population-based study in Peru with and without chronic exposure to biomass fuel smoke. Methods NT-pro-BNP levels were measured in 519 adults (275 with and 244 without chronic exposure to biomass fuel smoke). Participants answered sociodemographics and clinical history questionnaires, underwent a clinical examination and blood testing for cardiopulmonary biomarkers. PASP was measured in a subgroup of 153 (31%) subjects. Results The study group consisted of 280 men (54%) and 239 women (46%). Average age was 56 years and average body mass index was 27 kg/m2. In multivariable analysis, there was no association between chronic exposure to biomass fuel smoke and NT-pro-BNP (p=0.31) or PASP (p=0.31). In the subgroup in which both NT-pro-BNP levels and PASP were measured, there was strong evidence of an association between these two variables (ρ=0.24, 95% CI 0.09-0.39; p=0.003). We found that age, high sensitivity C-reactive protein, being male and systolic blood pressure were positively associated with NT-pro-BNP levels whereas body mass index, LDL/HDL ratio and HOMA-IR were negatively associated (all p<0.01). Conclusions In this population-based study in a high-altitude setting, neither NT-pro-BNP levels nor echocardiography-derived PASP were associated with chronic exposure to biomass fuel smoke. PMID:25440802

Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs their energy metabolism.

PubMed

Jin, Yuanxiang; Lin, Xiaojian; Miao, Wenyu; Wu, Tao; Shen, Hangjie; Chen, Shan; Li, Yanhong; Pan, Qiaoqiao; Fu, Zhengwei

2014-03-21

We evaluated the effects of a 20-week chronic exposure of mice to a low dose of cypermethrin (CYP), atrazine (ATZ) and 17α-ethynyestradiol (EE2) on energy metabolism. Here, male mice were exposed to 50 μg/kg BW/day CYP, 100 μg/kg BW/day ATZ or 1 μg/kg BW/day EE2 supplied in their drinking water for 20 weeks. During the exposure, mice were fed a high energy diet (HD). The bodyweights were not significantly affected by chronic exposure to EDCs, while the serum-free fatty acids (FFA) levels, hepatic lipid accumulation and triacylglycerol (TG) contents increased significantly in the ATZ- and CYP-HD groups. To determine the mechanism involved, we determined the expression levels of the genes in the glucose and fat metabolism pathways in the liver and adipose tissue. The results showed that chronic exposure to ATZ and CYP increased the mRNA levels of a number of key genes involved in both the de novo FFA synthesis pathway and the transport of FFA from blood. The increased amount of FFA was partially consumed as energy through β-oxidation in the mitochondria. Some of the FFA was used to synthesize TG in the liver by up-regulating primary genes, which resulted in increased TG levels and lipid accumulation. The results indicate that chronic exposure to EDCs has the potential to cause energy metabolic dysregulation and hepatotoxicity in mice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Airway responsiveness to methacholine, respiratory symptoms, and dust exposure levels in grain and flour mill workers in eastern France.

PubMed

Massin, N; Bohadana, A B; Wild, P; Kolopp-Sarda, M N; Toamain, J P

1995-06-01

Our goal was to assess the relation between dust exposure levels and the respiratory health status of workers in grain and flour mills in eastern France. We studied 118 male workers from 11 mills and 164 unexposed male controls. Dust concentration was measured by personal sampling methods. Outcome variables included respiratory symptoms, routine pulmonary function tests, and indices of airway responsiveness to methacholine. A great within- and between-area variability of inhalable dust concentration was found in all mills. A dose-response relationship was observed between dust exposure levels and chronic respiratory symptoms, suggesting that exposure to grain and flour dust may lead to chronic bronchitis. A significant relation was found between dust exposure and airway hyper-responsiveness; this finding is important since it has been hypothesized that the latter abnormality may lead to or be a predisposing factor in subsequent chronic, irreversible airflow obstruction.

A common neonicotinoid pesticide, thiamethoxam, impairs honey bee flight ability.

PubMed

Tosi, Simone; Burgio, Giovanni; Nieh, James C

2017-04-26

Pesticides can pose environmental risks, and a common neonicotinoid pesticide, thiamethoxam, decreases homing success in honey bees. Neonicotinoids can alter bee navigation, but we present the first evidence that neonicotinoid exposure alone can impair the physical ability of bees to fly. We tested the effects of acute or chronic exposure to thiamethoxam on the flight ability of foragers in flight mills. Within 1 h of consuming a single sublethal dose (1.34 ng/bee), foragers showed excitation and significantly increased flight duration (+78%) and distance (+72%). Chronic exposure significantly decreased flight duration (-54%), distance (-56%), and average velocity (-7%) after either one or two days of continuous exposure that resulted in bees ingesting field-relevant thiamethoxam doses of 1.96-2.90 ng/bee/day. These results provide the first demonstration that acute or chronic exposure to a neonicotinoid alone can significantly alter bee flight. Such exposure may impair foraging and homing, which are vital to normal colony function and ecosystem services.

Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice

NASA Astrophysics Data System (ADS)

Hu, Wei

Background: The medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol exposure is unknown. Here we explored the effects of acamprosate on an attentional set-shifting task, and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons. Methods: We induced alcohol dependence in mice via chronic intermittent ethanol (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2-bottle choice paradigm. Impairments of executive function were assessed in an attentional set-shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol-induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices. Results: Chronic ethanol exposure impaired cognitive flexibility in the attentional set-shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic ethanol exposure increased use-dependent presynaptic transmitter release and enhanced postsynaptic N-methyl-D-aspartate receptor (NMDAR) function. Moreover, CIE-treatment lowered input resistance, and decreased the threshold and the afterhyperpolarization (AHP) of action potentials, suggesting chronic ethanol exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these ethanol-induced changes cellular function. Conclusion: Acamprosate improved attentional control of ethanol exposed animals, but did not alter the concurrent changes in synaptic transmission or membrane excitability of mPFC neurons, indicating that these changes are not the pharmacological targets of acamprosate in the recovery of mPFC functions affected by chronic ethanol exposure.

Biomarkers for assessing potential carcinogenic effects of chronic arsenic exposure in Inner Mongolia, CHINA

EPA Science Inventory

Arsenic is ubiquitous in the environment. Chronic arsenic exposure via drinking water has been associated. with carcinogenic, cardiovascular, neurological and diabetic effects in humans and has been of great public health concern worldwide. In 2001, U.S. Environmental Protection ...

Marked heterogeneity in growth characteristics of myoblast clonal cultures and myoblast mixed cultures obtained from the same individual.

PubMed

Maier, Andrea B; Cohen, Ron; Blom, Joke; van Heemst, Diana; Westendorp, Rudi G J

2012-01-01

Sarcopenia is defined as an age-related decrease in skeletal muscle mass and function while adjacent satellite cells are unable to compensate for this loss. However, myoblast cultures can be established even in the presence of sarcopenia. It is yet unknown whether satellite cells from failing muscle in older age are equally affected, as human satellite cells have been assessed using myoblast mixed cultures and not by using myoblast clonal cultures. We questioned to what extent myoblast mixed cultures reflect the in vivo characteristics of single satellite cells from adult skeletal muscle. We established a myoblast mixed culture and three myoblast clonal cultures out of the same muscle biopsy and cultured these cells for 100 days. Replicative capacity and oxidative stress resistance were compared. We found marked heterogeneity between the myoblast clonal cultures that all had a significantly lower replicative capacity when compared to the mixed culture. Replicative capacity of the clonal cultures was inversely related to the β-galactosidase activity after exposure to oxidative stress. Addition of L-carnosine enhanced the remaining replicative capacity in all cultures with a concomitant marginal decrease in β-galactosidase activity. It is concluded that myoblast mixed cultures in vitro do not reflect the marked heterogeneity between single isolated satellite cells. The consequences of the heterogeneity on muscle performance remain to be established. Copyright © 2011 S. Karger AG, Basel.

Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

PubMed

Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V

2016-01-01

There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes.

PubMed

Rompala, Gregory R; Mounier, Anais; Wolfe, Cody M; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2 , known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development.

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes

PubMed Central

Rompala, Gregory R.; Mounier, Anais; Wolfe, Cody M.; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E.

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development. PMID:29472946

Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

PubMed

Bassi, Roberto; Niewczas, Monika A; Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D'Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

2017-01-01

Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

[The gastric mucosal adhesiveness of Z-103 in rats with chronic ulcer].

PubMed

Seiki, M; Aita, H; Mera, Y; Arai, K; Toyama, S; Furuta, S; Morita, H; Hori, Y; Yoneta, T; Tagashira, E

1992-04-01

The gastric mucosal adhesiveness of Z-103 in rats with acetic acid ulcer was studied macroscopically, histologically, and biochemically. From macroscopical observations, when Z-103 was orally administered to an acetic acid ulcer model, there was adhesion of Zn to the normal mucosa as well as the ulcerous site under both the fasting condition and after feeding. It was also proven that the strength and duration of adhesiveness were increased dose-dependently under fasting conditions. In addition, histological localization of Zn was noted from the covering epithelial cell layer to the gastric lamina propria mucosae in the normal tissue and in the most superficial ulcerous layer and the granulous layer of the ulcerous site. Measurement of the gastric tissue Zn content after oral administration of 100 mg/kg of Zn showed that the Zn content was significantly increased for 6 hr at the normal site and for 24 hr at the ulcerous site. On the other hand, although ZnSO4 and ZnSO4+carnosine combination macroscopically produced generally the same level of adhesiveness as Z-103, when the gastric tissue Zn content for Z-103 and ZnSO4 were compared, the Zn content of ZnSO4 was lower than that for Z-103 at both the normal and ulcerous site. In summary, Z-103 shows a long-term adhesive and permeable action on the gastric mucosa in acetic acid ulcer rats, and it has a comparable high affinity at the ulcerous site.

Identification of the key molecules involved in chronic copper exposure-aggravated memory impairment in transgenic mice of Alzheimer's disease using proteomic analysis.

PubMed

Yu, Jun; Luo, Xiaobin; Xu, Hua; Ma, Quan; Yuan, Jianhui; Li, Xuling; Chang, Raymond Chuen-Chung; Qu, Zhongsen; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

2015-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by a progressive impairment of cognitive functions including spatial learning and memory. Excess copper exposure accelerates the development of AD; however, the potential mechanisms by which copper exacerbates the symptoms of AD remain unknown. In this study, we explored the effects of chronic copper exposure on cognitive function by treating 6 month-old triple AD transgenic (3xTg-AD) mice with 250 ppm copper sulfate in drinking water for 6 months, and identified several potential key molecules involved in the effects of chronic copper exposure on memory by proteomic analysis. The behavioral test showed that chronic copper exposure aggravated memory impairment of 3xTg-AD mice. Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry revealed a total of 44 differentially expressed proteins (18 upregulated and 26 down-regulated) in hippocampus between the wild-type (WT) mice and non-exposed 3xTg-AD mice. A total of 40 differentially expressed proteins were revealed (20 upregulated and 20 down-regulated) in hippocampus between copper exposed and non-exposed 3xTg-AD mice. Among these differentially expressed proteins, complexin-1 and complexin-2, two memory associated proteins, were significantly decreased in hippocampus of 3xTg-AD mice compared with the WT mice. Furthermore, the expression of these two proteins was further down-regulated in 3xTg-AD mice when exposed to copper. The abnormal expression of complexin-1 and complexin-2 identified by proteomic analysis was verified by western blot analysis. Taken together, our data showed that chronic copper exposure accelerated memory impairment and altered the expression of proteins in hippocampus in 3xTg-AD mice. The functional analysis on the differentially expressed proteins suggested that complexin-1 and complexin-2 may be the key molecules involved in chronic copper exposure-aggravated memory impairment in AD.

Acute and chronic toxicity of nickel to rainbow trout (Oncorhynchus mykiss).

PubMed

Brix, Kevin V; Keithly, James; DeForest, David K; Laughlin, Jim

2004-09-01

Of the fish species tested in chronic Ni exposures, rainbow trout (Oncorhynchus mykiss) is the most sensitive. To develop additional Ni toxicity data and to investigate the toxic mode of action for Ni, we conducted acute (96-h) and chronic (85-d early life-stage) flow-through studies using rainbow trout. In addition to standard toxicological endpoints, we investigated the effects of Ni on ionoregulatory physiology (Na, Ca, and Mg). The acute median lethal concentration for Ni was 20.8 mg/L, and the 24-h gill median lethal accumulation was 666 nmol/g wet weight. No effects on plasma Ca, Mg, or Na were observed during acute exposure. In the chronic study, no significant effects on embryo survival, swim-up, hatching, or fingerling survival or growth were observed at dissolved Ni concentrations up to 466 microg/L, the highest concentration tested. This concentration is considerably higher than the only other reported chronic no-observed-effect concentration (<33 microg/L) for rainbow trout. Accumulation of Ni in trout eggs indicates the chorion is only a partial barrier with 36%, 63%, and 1% of total accumulated Ni associated with the chorion, yolk, and embryo, respectively. Whole-egg ion concentrations were reduced by Ni exposure. However, most of this reduction occurred in the chorion rather than in the embryos, and no effects on hatching success or larval survival were observed as a result. Plasma ion concentrations measured in swim-up fingerlings at the end of the chronic-exposure period were not significantly reduced by exposure to Ni. Nickel accumulated on the gill in an exponential manner but plateaued in trout plasma at waterborne Ni concentrations of 118 microg/L or greater. Consistent with previous studies, Ni did not appear to disrupt ionoregulation in acute exposures of rainbow trout. Our results also suggest that Ni is not an ionoregulatory toxicant in long-term exposures, but the lack of effects in the highest Ni treatment precludes a definitive conclusion.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures

USGS Publications Warehouse

Kunz, James L.; Ingersoll, Christopher G.; Smalling, Kelly; Elskus, Adria; Kuivila, Kathryn

2017-01-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubiaand L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. aztecareproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;9999:1–8. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

The promise and challenge of virtual gaming technologies for chronic pain: the case of graded exposure for low back pain.

PubMed

Trost, Zina; Zielke, Marjorie; Guck, Adam; Nowlin, Liza; Zakhidov, Djanhangir; France, Christopher R; Keefe, Francis

2015-01-01

Virtual reality (VR) technologies have been successfully applied to acute pain interventions and recent reviews have suggested their potential utility in chronic pain. The current review highlights the specific relevance of VR interactive gaming technologies for pain-specific intervention, including their current use across a variety of physical conditions. Using the example of graded-exposure treatment for pain-related fear and disability in chronic low back pain, we discuss ways that VR gaming can be harnessed to optimize existing chronic pain therapies and examine the potential limitations of traditional VR interfaces in the context of chronic pain. We conclude by discussing directions for future research on VR-mediated applications in chronic pain.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

PubMed Central

da Silva, Fernando B. R.; Cunha, Polyane A.; Ribera, Paula C.; Barros, Mayara A.; Cartágenes, Sabrina C.; Fernandes, Luanna M. P.; Teixeira, Francisco B.; Fontes-Júnior, Enéas A.; Prediger, Rui D.; Lima, Rafael R.; Maia, Cristiane S. F.

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats.

PubMed

da Silva, Fernando B R; Cunha, Polyane A; Ribera, Paula C; Barros, Mayara A; Cartágenes, Sabrina C; Fernandes, Luanna M P; Teixeira, Francisco B; Fontes-Júnior, Enéas A; Prediger, Rui D; Lima, Rafael R; Maia, Cristiane S F

2018-01-01

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures' morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Exposure to cold and draught, alcohol consumption, and the NS-phenotype are associated with chronic bronchitis: an epidemiological investigation of 3387 men aged 53-75 years: the Copenhagen Male Study.

PubMed

Suadicani, P; Hein, H O; Meyer, H W; Gyntelberg, F

2001-03-01

This study was performed to estimate the strength of association between chronic bronchitis and lifetime exposure to occupational factors, current lifestyle, and the NS-phenotype in the MNS blood group among middle aged and elderly men. The study was carried out within the frameworks of the Copenhagen Male Study. Of 3387 men 3331 men with a mean age of 63 (range 53-75) years could be classified by prevalence of chronic bronchitis. As well as the completion of a large questionnaire on health, lifestyle, and working conditions, all participants had a thorough examination, including measurements of height and weight and blood pressure and a venous blood sample was taken for the measurement of serum cotinine and MNS typing; 16.5% of the men had the NS-phenotype. Chronic bronchitis was defined as cough and phlegm lasting 3 months or more for at least 2 years; 14.6% had chronic bronchitis. Smoking and smoke inhalation were the factors most strongly associated with prevalence of chronic bronchitis. There were three major new findings: (a) long term (>5 years) occupational exposure to cold and draught was associated with a significantly increased prevalence of chronic bronchitis; compared with others, and adjusted for confounders, the odds ratio (OR) with 95% confidence interval (95% CI) was 1.4 (1.1 to 1.7), p=0.004; (b) a significant J shaped association existed between alcohol use and bronchitis, p<0.001, with the lowest prevalence found among moderate users; (c) a significant gene by environment association existed between smoking and the NS-phenotype in the MNS blood group; only among smokers was the NS-phenotype associated with a significantly decreased risk of chronic bronchitis, OR 0.67 (0.47-0.97), p=0.02. Other well known associations between dust, fumes, and even exposure to solvents and bronchitis were confirmed. The results emphasise the multifactorial nature of chronic bronchitis, and show some hitherto unrecognised associations between cold and draught exposure, alcohol consumption, and the NS-phenotype and chronic bronchitis.

Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats.

PubMed

Der-Avakian, Andre; Markou, Athina

2010-07-01

Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent decrease in motivated behavior, which was not correlated with body weight loss. Social interaction was not affected during withdrawal from either drug. These results indicate that withdrawal from chronic amphetamine exposure leads to an immediate and enduring anhedonic state.

Molecular, cellular, and tissue impact of depleted uranium on xenobiotic-metabolizing enzymes.

PubMed

Gueguen, Yann; Rouas, Caroline; Monin, Audrey; Manens, Line; Stefani, Johanna; Delissen, Olivia; Grison, Stéphane; Dublineau, Isabelle

2014-02-01

Enzymes that metabolize xenobiotics (XME) are well recognized in experimental models as representative indicators of organ detoxification functions and of exposure to toxicants. As several in vivo studies have shown, uranium can alter XME in the rat liver or kidneys after either acute or chronic exposure. To determine how length or level of exposure affects these changes in XME, we continued our investigation of chronic rat exposure to depleted uranium (DU, uranyl nitrate). The first study examined the effect of duration (1-18 months) of chronic exposure to DU, the second evaluated dose dependence, from a level close to that found in the environment near mining sites (0.2 mg/L) to a supra-environmental dose (120 mg/L, 10 times the highest level naturally found in the environment), and the third was an in vitro assessment of whether DU exposure directly affects XME and, in particular, CYP3A. The experimental in vivo models used here demonstrated that CYP3A is the enzyme modified to the greatest extent: high gene expression changed after 6 and 9 months. The most substantial effects were observed in the liver of rats after 9 months of exposure to 120 mg/L of DU: CYP3A gene and protein expression and enzyme activity all decreased by more than 40 %. Nonetheless, no direct effect of DU by itself was observed after in vitro exposure of rat microsomal preparations, HepG2 cells, or human primary hepatocytes. Overall, these results probably indicate the occurrence of regulatory or adaptive mechanisms that could explain the indirect effect observed in vivo after chronic exposure.

Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

PubMed

Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

2012-11-01

The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time.

The costs of chronic noise exposure for terrestrial organisms.

PubMed

Barber, Jesse R; Crooks, Kevin R; Fristrup, Kurt M

2010-03-01

Growth in transportation networks, resource extraction, motorized recreation and urban development is responsible for chronic noise exposure in most terrestrial areas, including remote wilderness sites. Increased noise levels reduce the distance and area over which acoustic signals can be perceived by animals. Here, we review a broad range of findings that indicate the potential severity of this threat to diverse taxa, and recent studies that document substantial changes in foraging and anti-predator behavior, reproductive success, density and community structure in response to noise. Effective management of protected areas must include noise assessment, and research is needed to further quantify the ecological consequences of chronic noise exposure in terrestrial environments.

Anxiogenic-like effects of chronic nicotine exposure in zebrafish.

PubMed

Stewart, Adam Michael; Grossman, Leah; Collier, Adam D; Echevarria, David J; Kalueff, Allan V

2015-12-01

Nicotine is one of the most widely used and abused legal drugs. Although its pharmacological profile has been extensively investigated in humans and rodents, nicotine CNS action remains poorly understood. The importance of finding evolutionarily conserved signaling pathways, and the need to apply high-throughput in vivo screens for CNS drug discovery, necessitate novel efficient experimental models for nicotine research. Zebrafish (Danio rerio) are rapidly emerging as an excellent organism for studying drug abuse, neuropharmacology and toxicology and have recently been applied to testing nicotine. Anxiolytic, rewarding and memory-modulating effects of acute nicotine treatment in zebrafish are consistently reported in the literature. However, while nicotine abuse is more relevant to long-term exposure models, little is known about chronic effects of nicotine on zebrafish behavior. In the present study, chronic 4-day exposure to 1-2mg/L nicotine mildly increased adult zebrafish shoaling but did not alter baseline cortisol levels. We also found that chronic exposure to nicotine evokes robust anxiogenic behavioral responses in zebrafish tested in the novel tank test paradigm. Generally paralleling clinical and rodent data on anxiogenic effects of chronic nicotine, our study supports the developing utility of zebrafish for nicotine research. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in gene expression in chronic allergy mouse model exposed to natural environmental PM2.5-rich ambient air pollution.

PubMed

Ouyang, Yuhui; Xu, Zhaojun; Fan, Erzhong; Li, Ying; Miyake, Kunio; Xu, Xianyan; Zhang, Luo

2018-04-20

Particulate matter (PM) air pollution has been associated with an increase in the incidence of chronic allergic diseases; however, the mechanisms underlying the effect of exposure to natural ambient air pollution in chronic allergic diseases have not been fully elucidated. In the present study, we aimed to investigate the cellular responses induced by exposure to natural ambient air pollution, employing a mouse model of chronic allergy. The results indicated that exposure to ambient air pollution significantly increased the number of eosinophils in the nasal mucosa. The modulation of gene expression profile identified a set of regulated genes, and the Triggering Receptor Expressed on Myeloid cells1(TREM1) signaling canonical pathway was increased after exposure to ambient air pollution. In vitro, PM2.5 increased Nucleotide-binding oligomerization domain-containing protein 1 (Nod1) and nuclear factor (NF)-κB signaling pathway activation in A549 and HEK293 cell cultures. These results suggest a novel mechanism by which, PM2.5 in ambient air pollution may stimulate the innate immune system through the PM2.5-Nod1-NF-κB axis in chronic allergic disease.

Modeling Nuclear Receptor-Mediated Activity and Hepatotoxicity with Boolean Networks

EPA Science Inventory

Predicting the human health risk of chronic exposure to environmental contaminants remains an open problem. Chronic exposure to a wide array of chemicals – e.g., conazoles, perfluourinated chemicals and phthalates – has been associated with a range of hepatic lesions in rodents t...

Effects of a Chronic Lower Range of Triclosan Exposure on a Stream Mesocosm Community

EPA Science Inventory

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is an antimicrobial found in consumer soaps and toothpaste. It is in treated wastewater effluents at low part per billion concentrations, representing a potentially chronic exposure condition for biota inhabiting receiving strea...

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.

EPA Science Inventory

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. ME Gilbert1, ME Kelly2, S. Salant3, T Shafer1, J Goodman3 1Neurotoxicology Div, US EPA, RTP, NC, 27711, 2Children's Hospital, Philadelphia, PA, 19104, 3Helen Hayes Hospital, Haverstraw, NY, 10993.
...

SMALL AIRWAYS FUNCTION RESPONSE IN SMOKERS AND PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT AIR PARTICLES

EPA Science Inventory

Numerous field and epidemiological studies have shown significant associations between particulate matter (PM) exposure and various morbidity outcomes including hospital admissions for bronchitis and asthma. These population based studies indicate that persons with chronic obstru...

Use of a 15 k gene microarray to determine gene expression changes in response to acute and chronic methylmercury exposure in the fathead minnow Pimephales promelas Rafinesque

USGS Publications Warehouse

Klaper, R.; Carter, Barbara J.; Richter, C.A.; Drevnick, P.E.; Sandheinrich, M.B.; Tillitt, D.E.

2008-01-01

This study describes the use of a 15 000 gene microarray developed for the toxicological model species, Pimephales promelas, in investigating the impact of acute and chronic methylmercury exposures in male gonad and liver tissues. The results show significant differences in the individual genes that were differentially expressed in response to each treatment. In liver, a total of 650 genes exhibited significantly (P < 0.05) altered expression with greater than two-fold differences from the controls in response to acute exposure and a total of 267 genes were differentially expressed in response to chronic exposure. A majority of these genes were downregulated rather than upregulated. Fewer genes were altered in gonad than in liver at both timepoints. A total of 212 genes were differentially expressed in response to acute exposure and 155 genes were altered in response to chronic exposure. Despite the differences in individual genes expressed across treatments, the functional categories that altered genes were associated with showed some similarities. Of interest in light of other studies involving the effects of methylmercury on fish, several genes associated with apoptosis were upregulated in response to both acute and chronic exposures. Induction of apoptosis has been associated with effects on reproduction seen in the previous studies. This study demonstrates the utility of microarray analysis for investigations of the physiological effects of toxicants as well as the time-course of effects that may take place. In addition, it is the first publication to demonstrate the use of this new 15 000 gene microarray for fish biology and toxicology. ?? 2008 The Authors.

Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

PubMed

Stier, Antoine; Massemin, Sylvie; Criscuolo, François

2014-12-01

Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

PubMed

Flores-Montoya, Mayra Gisel; Sobin, Christina

2015-07-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). Copyright © 2014 John Wiley & Sons, Ltd.

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

PubMed Central

Flores-Montoya, Mayra Gisel; Sobin, Christina

2014-01-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1. PMID:25219894

Effects of acute and chronic exposure to both 900 MHz and 2100 MHz electromagnetic radiation on glutamate receptor signaling pathway.

PubMed

Gökçek-Saraç, Çiğdem; Er, Hakan; Kencebay Manas, Ceren; Kantar Gok, Deniz; Özen, Şükrü; Derin, Narin

2017-09-01

To demonstrate the molecular effects of acute and chronic exposure to both 900 and 2100 MHz radiofrequency electromagnetic radiation (RF-EMR) on the hippocampal level/activity of some of the enzymes - including PKA, CaMKIIα, CREB, and p44/42 MAPK - from N-methyl-D-aspartate receptor (NMDAR)-related signaling pathways. Rats were divided into the following groups: sham rats, and rats exposed to 900 and 2100 MHz RF-EMR for 2 h/day for acute (1 week) or chronic (10 weeks), respectively. Western blotting and activity measurement assays were used to assess the level/activity of the selected enzymes. The obtained results revealed that the hippocampal level/activity of selected enzymes was significantly higher in the chronic groups as compared to the acute groups at both 900 and 2100 MHz RF-EMR exposure. In addition, hippocampal level/activity of selected enzymes was significantly higher at 2100 MHz RF-EMR than 900 MHz RF-EMR in both acute and chronic groups. The present study provides experimental evidence that both exposure duration (1 week versus 10 weeks) and different carrier frequencies (900 vs. 2100 MHz) had different effects on the protein expression of hippocampus in Wistar rats, which might encourage further research on protection against RF-EMR exposure.

Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis.

PubMed

Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Williams, Timothy; Ting, Hua; Lee, Shin-Da

2014-06-01

Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.

Evaluation of the serum catalase and myeloperoxidase activities in chronic arsenic-exposed individuals and concomitant cytogenetic damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banerjee, Mayukh; Banerjee, Nilanjana; Ghosh, Pritha

2010-11-15

Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA damage that might ultimately culminate in cancer. In order to keep the level of ROS in balance, an array of enzymes is present, of which catalase (CAT) and myeloperoxidase (MPO) are important members. Hence, in this study, we determined the activities of these two enzymes in the seramore » and chromosomal aberrations (CA) in peripheral blood lymphocytes in individuals exposed and unexposed to arsenic in drinking water. Arsenic in drinking water and in urine was used as a measure of exposure. Our results show that individuals chronically exposed to arsenic have significantly higher CAT and MPO activities and higher incidence of CA. We found moderate positive correlations between CAT and MPO activities, induction of CA and arsenic in urine and water. These results indicate that chronic arsenic exposure causes higher CAT and MPO activities in serum that correlates with induction of genetic damage. We conclude that the serum levels of these enzymes might be used as biomarkers of early arsenic exposure induced disease much before the classical dermatological symptoms of arsenicosis begin to appear.« less

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

PubMed

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M; Wilks, Martin F; Spandidos, Demetrios A; Fenga, Concettina

2016-10-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well‑designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review)

PubMed Central

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M.; Wilks, Martin F.; Spandidos, Demetrios A.; Fenga, Concettina

2016-01-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well-designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases. PMID:27600395

Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review.

PubMed

Yoshida, Takahiko; Yamauchi, Hiroshi; Fan Sun, Gui

2004-08-01

Chronic arsenic (As) poisoning has become a worldwide public health issue. Most human As exposure occurs from consumption of drinking water containing high amounts of inorganic As (iAs). In this paper, epidemiological studies conducted on the dose-response relationships between iAs exposure via the drinking water and related adverse health effects are reviewed. Before the review, the methods for evaluation of the individual As exposure are summarized and classified into two types, that is, the methods depending on As concentration of the drinking water and the methods depending on biological monitoring for As exposure; certain methods may be applied as optimum As exposure indexes to study dose-response relationship based on various As exposure situation. Chronic effects of iAs exposure via drinking water include skin lesions, neurological effects, hypertension, peripheral vascular disease, cardiovascular disease, respiratory disease, diabetes mellitus, and malignancies including skin cancer. The skin is quite sensitive to arsenic, and skin lesions are some of the most common and earliest nonmalignant effects related to chronic As exposure. The increase of prevalence in the skin lesions has been observed even at the exposure levels in the range of 0.005-0.01 mg/l As in drinking waters. Skin, lung, bladder, kidney, liver, and uterus are considered as sites As-induced malignancies, and the skin is though to be perhaps the most sensitive site. Prospective studies in large area of endemic As poisoning, like Bangladesh or China, where the rate of malignancies is expected to increase within the next several decades, will help to clarify the dose-response relationship between As exposure levels and adverse health effects with enhanced accuracy.

APOPTOSIS GENE EXPRESSION IN HUMAN EPDERMAL KERATINOCYTES TREATED WITH SODIUM ARSENITE USING REAL TIME PCR ARRAY

EPA Science Inventory

Arsenic exposure via contaminated drinking water is a great public health concern worldwide. Chronic arsenic exposure has been associated with human skin, lung and bladder cancer and other chronic effects. We have previous reported that sodium arsenite stimulated cell proliferati...

AN "INJURY-TIME INTEGRAL" MODEL FOR RELATING ACUTE TO CHRONIC INJURY TO PHOSGENE

EPA Science Inventory

ABSTRACT
The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the "concentration x time" (C x T) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (m...

CHRONIC EXPOSURE OF RATS TO 100-MHZ (CW) RADIOFREQUENCY RADIATION: ASSESSMENT OF BIOLOGICAL EFFECTS

EPA Science Inventory

A multidisciplinary approach was employed to assess the possible biological effects of chronic exposure of rats to 100-MHz continuous wave (CW) radiofrequency (RF) radiation. A group of 20 time-bred rats were exposed in a transverse electronmagnetic mode (TEM) transmission line t...

Acute and chronic respiratory effects of sodium borate particulate exposures.

PubMed Central

Wegman, D H; Eisen, E A; Hu, X; Woskie, S R; Smith, R G; Garabrant, D H

1994-01-01

This study examined work-related chronic abnormality in pulmonary function and work-related acute irritant symptoms associated with exposure to borate dust in mining and processing operations. Chronic effects were examined by pulmonary function at the beginning and end of a 7-year interval. Time-specific estimates of sodium borate particulate exposures were used to estimate cumulative exposure during the study interval. Change in pulmonary function over the 7 years was found unrelated to the estimate of cumulative exposure during that interval. Exposure-response associations also were examined with respect to short-term peak exposures and incidence of five symptoms of acute respiratory irritation. Hourly measures of health outcome and continuous measures of particulate exposure were made on each subject throughout the day. Whenever a subject reported one of the irritant symptoms, a symptom intensity score was also recorded along with the approximate time of onset. The findings indicated that exposure-response relationships were present for each of the specific symptoms at several symptom intensity levels. The associations were present when exposure was estimated by both day-long and short-term (15-min) time-weighted average exposures. Associations persisted after taking account of smoking, age, and the presence of a common cold. No significant difference in response rate was found between workers exposed to different types of sodium borate dusts. PMID:7889871

Combined endosulfan and cypermethrin-induced toxicity to embryo-larval development of Rhinella arenarum.

PubMed

Svartz, Gabriela V; Aronzon, Carolina M; Pérez Coll, Cristina S

2016-01-01

The combined effects of two widely used pesticides, endosulfan and cypermethrin, on survival of embryo-larval development of the South American toad (Rhinella arenarum) were examined. The toxicity bioassays were performed according to the AMPHITOX test. Embryos and larvae were exposed to mixtures of these pesticides at equitoxic ratios from acute or chronic exposure to evaluate interaction effects. The results were analyzed using both Marking's additive index and combination index (CI)-isobologram methods. Acute (96-h) and intermediate (168-h) toxicity of endosulfan-cypermethrin mixtures remained almost constant for larvae and embryos, but when exposure duration was increased, there was a significant elevation in toxicity, obtaining chronic (240-h) no-observed-effect concentrations (NOEC) values of 0.045 and 0.16 mg/L for embryos and larvae, respectively. These are environmentally relevant concentrations that reflect a realistic risk of this pesticide mixture to this native amphibian species. The toxicity increment with the exposure duration was coincident with the central nervous system development on embryos reaching the larval period, the main target organ of these pesticides. The interactions of the pesticide mixtures at acute and chronic exposure were antagonistic for embryo development (CI > 1), and additive (CI = 1) for larvae, while chronic exposure interactions were synergistic (CI < 1) for both developmental periods. Data indicated that endosulfan-cypermethrin mixtures resulted in different interaction types depending on duration and developmental stage exposed. As a general pattern and considering conditions of overall developmental period and chronic exposure, this pesticide mixture usually applied in Argentine crop fields is synergistic with respect to toxicity for this native amphibian species.

Acute and Chronic Ethanol Exposure Differentially Regulate CB1 Receptor Function at Glutamatergic Synapses in the Rat Basolateral Amygdala

PubMed Central

Robinson, Stacey L.; Alexander, Nancy J.; Bluett, Rebecca J.; Patel, Sachin; McCool, Brian A.

2016-01-01

The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

Association between hepatitis C infection and cerebro-cardiovascular disease: analysis of a national population-based survey in Egypt.

PubMed

Gadallah, Mohsen; Kandil, Sahar; Mohsen, Amira

2018-05-03

To examine the association between hepatitis C virus (HCV) infection, cardiovascular risk factors and cerebro-cardiovascular (CCV) disease. The source of data was the Egypt Health Issues Survey conducted in 2015. Participants were 11 256 individuals with complete HCV testing, age 25-59 years. Data on demographics, cardiovascular risk factors, CCV disease (myocardial infarction and/or cerebral stroke) and HCV infection were retrieved. Descriptive, bivariate, multivariable logistic regression and sensitivity analyses were performed to determine the independent association of past HCV exposure or chronic infection with diabetes, hypertension and CCV disease. 3.9% of participants were antibody positive/RNA negative and considered to have past HCV exposure; 7.9% had detectable HCV-RNA and were considered to have chronic infection. Participants with negative antibodies and no history of liver disease (n = 9928) were the control group. In addition to the previously known risk factors, multivariable analyses revealed that diabetes was independently associated with past HCV exposure (OR = 1.71, 95% CI: 1.27-2.32) and HCV chronic infection (OR = 1.56, 95% CI: 1.23-1.97), whereas CCV disease was independently associated with past exposure (OR = 2.69, 95% CI: 1.62-4.46) and not with chronic infection. No evidence of an association between hypertension and either HCV status was found. The association of both past HCV exposure and chronic infection with diabetes and that of past HCV exposure with CCV disease may suggest targeting HCV-positive reactors for preventive and curative programmes addressing extrahepatic complications. © 2018 John Wiley & Sons Ltd.

Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

PubMed

Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

2013-12-01

The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

Evidence for a dipolar-coupled AM system in carnosine in human calf muscle from in vivo 1H NMR spectroscopy

NASA Astrophysics Data System (ADS)

Schröder, Leif; Bachert, Peter

2003-10-01

Spin systems with residual dipolar couplings such as creatine, taurine, and lactate in skeletal muscle tissue exhibit first-order spectra in in vivo 1H NMR spectroscopy at 1.5 T because the coupled protons are represented by (nearly) symmetrized eigenfunctions. The imidazole ring protons (H2, H4) of carnosine are suspected to form also a coupled system. The ring's stiffness could enable a connectivity between these anisochronous protons with the consequence of second-order spectra at low field strength. Our purpose was to study whether this deviation from the Paschen-Back condition can be used to detect the H2-H4 coupling in localized 1D 1H NMR spectra obtained at 1.5 T (64 MHz) from the human calf in a conventional whole-body scanner. As for the hydrogen hyperfine interaction, a Breit-Rabi equation was derived to describe the transition from Zeeman to Paschen-Back regime for two dipolar-coupled protons. The ratio of the measurable coupling strength ( Sk) and the difference in resonance frequencies of the coupled spins (Δ ω) induces quantum-state mixing of various degree upon definition of an appropriate eigenbase of the coupled spin system. The corresponding Clebsch-Gordan coefficients manifest in characteristic energy corrections in the Breit-Rabi formula. These additional terms were used to define an asymmetry parameter of the line positions as a function of Sk and Δ ω. The observed frequency shifts of the resonances were found to be consistent with this parameter within the accuracy achievable in in vivo NMR spectroscopy. Thus it was possible to identify the origin of satellite peaks of H2, H4 and to describe this so far not investigated type of residual dipolar coupling in vivo.

Evidence for the role of histaminergic pathways in neuroprotective mechanism of ischemic postconditioning in mice.

PubMed

Kaur, Indresh; Kumar, Amit; Jaggi, Amteshwar S; Singh, Nirmal

2017-08-01

The present study has been designed to investigate the possible role of histaminergic pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo). Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was employed to produce I/R-induced cerebral injury in National Institutes of Health mice mice. iPoCo involving three episodes of carotid artery occlusion and reperfusion of 10 sec each was instituted immediately after BCAO just before prolonged reperfusion. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using Morris water maze test. Rotarod test, inclined beam-walking test, and neurological severity score (NSS) were performed to assess motor incoordination and sensorimotor abilities. Brain acetylcholine esterase (AChE) activity, brain myeloperoxidase (MPO) activity, brain thiobarbituric acid-reactive species (TBARS), and glutathione level (GSH) were also estimated. BCAO produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑AChE, ↑MPO ↓GSH, and ↑TBARS). iPoCo attenuated the deleterious effect of BCAO on infarct size, memory, NSS, motor coordination, and biochemical markers. Pretreatment of carnosine (a histamine [HA] precursor) potentiated the neuroprotective effects of iPoCo, whereas pretreatment of ketotifen (HA H1 receptor blocker and mast cell stabilizer) abolished the protective effects of iPoCo as well as that of carnosine on iPoCo. It may be concluded that neuroprotective effect of iPoCo probably involves activation of histaminergic pathways. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Zinc-carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis.

PubMed

Wilson, Laura S; Rosenkrantz, Wayne S; Roycroft, Linda M

2011-02-01

Chelated zinc-carnosine and vitamin E [GastriCalm(®) (GCM); Teva Animal Health] is marketed as an anti-emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double-blinded, placebo-controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica(®); Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n=30) or placebo (n=30) groups. All dogs received ∼ 5 mg/kg ciclosporin (range, 3.5-5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs ≥ 13.6 kg received one tablet once daily. GastriCalm(®) or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty-one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty-seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P=0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P<0.05). © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

Antioxidant status of turkey breast meat and blood after feeding a diet enriched with histidine.

PubMed

Kopec, W; Wiliczkiewicz, A; Jamroz, D; Biazik, E; Pudlo, A; Hikawczuk, T; Skiba, T; Korzeniowska, M

2016-01-01

The objective of this study was to investigate the effects of 1) spray dried blood cells rich in histidine and 2) pure histidine added to feed on the antioxidant status and concentration of carnosine related components in the blood and breast meat of female turkeys. The experiment was performed on 168 Big7 turkey females randomly assigned to 3 dietary treatments: control; control with the addition of 0.18% L-histidine (His); and control with the addition of spray dried blood cells (SDBC). Birds were raised for 103 d on a floor with sawdust litter, with drinking water and feed ad libitum. The antioxidant status of blood plasma and breast muscle was analyzed by ferric reducing ability (FRAP) and by 2,2-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals scavenging ability. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was analyzed in the blood and breast meat, with the content of carnosine and anserine quantified by HPLC. Proximate analysis as well as amino acid profiling were carried out for the feed and breast muscles. Growth performance parameters also were calculated. Histidine supplementation of the turkey diet resulted in increased DPPH radical scavenging capacity in the breast muscles and blood, but did not result in higher histidine dipeptide concentrations. The enzymatic antioxidant system of turkey blood was affected by the diet with SDBC. In the plasma, the SDBC addition increased both SOD and GPx activity, and decreased GPx activity in the erythrocytes. Feeding turkeys with an SDBC containing diet increased BW and the content of isoleucine and valine in breast muscles. © 2015 Poultry Science Association Inc.

Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

PubMed

Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

2017-02-01

Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study.

PubMed

Argos, Maria; Kalra, Tara; Rathouz, Paul J; Chen, Yu; Pierce, Brandon; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; van Geen, Alexander; Graziano, Joseph; Ahsan, Habibul

2010-07-24

Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure. US National Institutes of Health. Copyright 2010 Elsevier Ltd. All rights reserved.

Lung Inflammation, Injury, and Proliferative Response after Repetitive Particulate Hexavalent Chromium Exposure

PubMed Central

Beaver, Laura M.; Stemmy, Erik J.; Schwartz, Arnold M.; Damsker, Jesse M.; Constant, Stephanie L.; Ceryak, Susan M.; Patierno, Steven R.

2009-01-01

Background Chronic inflammation is implicated in the development of several human cancers, including lung cancer. Certain particulate hexavalent chromium [Cr(VI)] compounds are well-documented human respiratory carcinogens that release genotoxic soluble chromate and are associated with fibrosis, fibrosarcomas, adenocarcinomas, and squamous cell carcinomas of the lung. Despite this, little is known about the pathologic injury and immune responses after repetitive exposure to particulate chromates. Objectives In this study we investigated the lung injury, inflammation, proliferation, and survival signaling responses after repetitive exposure to particulate chromate. Methods BALB/c mice were repetitively treated with particulate basic zinc chromate or saline using an intranasal exposure regimen. We assessed lungs for Cr(VI)-induced changes by bronchoalveolar lavage, histologic examination, and immunohistochemistry. Results Single exposure to Cr(VI) resulted in inflammation of lung tissue that persists for up to 21 days. Repetitive Cr(VI) exposure induced a neutrophilic inflammatory airway response 24 hr after each treatment. Neutrophils were subsequently replaced by increasing numbers of macrophages by 5 days after treatment. Repetitive Cr(VI) exposure induced chronic peribronchial inflammation with alveolar and interstitial pneumonitis dominated by lymphocytes and macrophages. Moreover, chronic toxic mucosal injury was observed and accompanied by increased airway pro-matrix metalloprotease-9. Injury and inflammation correlated with airways becoming immunoreactive for phosphorylation of the survival signaling protein Akt and the proliferation marker Ki-67. We observed a reactive proliferative response in epithelial cells lining airways of chromate-exposed animals. Conclusions These data illustrate that repetitive exposure to particulate chromate induces chronic injury and an inflammatory microenvironment that may promote Cr(VI) carcinogenesis. PMID:20049209

[Methylmethacrylate and organic dementia. A dose-response analysis among dental technicians and opticians].

PubMed

Steendahl, U; Prescott, E; Damsgaard, M T

1992-05-11

The substance methylmethacrylate (MMA) is an organic solvent which is employed inter alii for prostheses which is suspected of being neurotoxic. With the object of illustrating whether there is a connection between exposure to MMA and symptoms of organic dementia, a cross-sectional investigation was carried out on a population consisting of occupationally active dental technicians and opticians (n = 528) and a group of dental technicians who were no longer occupationally active (n = 173). No noteworthy difference in the background variables, apart from age, was observed. Age was taken into consideration in the analysis. The results show a statistically significant increase in the prevalence of the chronic symptoms on increasing exposure. Where the acute symptoms are concerned, the connection is not statistically significant, but a tendency is observed. A chronic symptom index constructed on the basis of 13 questions concerning chronic symptoms is compared with the life exposure and the age. A statistically significant increase in the index was found with exposure to MMA, although not for the oldest age group. The pattern symptoms, presence of bias and other forms of exposure are discussed. It is concluded that this investigation confirms the hypothesis that symptoms of organic dementia have a connection the exposure to MMA. The results support the presumption that MMA causes acute and chronic damage to the central nervous system even with exposure below the safety limits. It is recommended that the occupational environment of dental technicians, including the present safety limits, should be revised.

Sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells in mice

PubMed Central

Guo, Chang-Ying; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Huang, Wen-Jing; Takamura, Syu; Hayashi, Fumiko; Doi, Hanako; Kitajima, Yuriko; Ono, Yusuke; Ogi, Tomoo; Li, Tao-Sheng

2015-01-01

We evaluated the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells. Adult C57BL/6 mice were daily exposed to 0, 2, 10, 50, and 250 mGy γ-ray for 1 month in succession, respectively. The damage of hematopoietic stem/progenitor cells in bone marrow were investigated within 2 hours (acute phase) or at 3 months (chronic phase) after the last exposure. Daily exposure to over 10 mGy γ-ray significantly decreased the number and colony-forming capacity of hematopoietic stem/progenitor cells at acute phase, and did not completely recover at chronic phase with 250 mGy exposure. Interestingly, the daily exposure to 10 or 50 mGy γ-ray decreased the formation of mixed types of colonies at chronic phase, but the total number of colonies was comparable to control. Immunostaining analysis showed that the formation of 53BP1 foci in c-kit+ stem/progenitor cells was significantly increased with daily exposure to 50 and 250 mGy at acute phase, and 250 mGy at chronic phase. Many genes involved in toxicity responses were up- or down-regulated with the exposures to all doses. Our data have clearly shown the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells of mice with daily exposures to 2 ~ 250 mGy γ-ray. PMID:25623887

Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

PubMed

Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

2016-05-01

Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety/compulsive-like behaviors may be driven by greater kappa opioid receptor sensitivity and a hypodopaminergic state of the nucleus accumbens. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Pesticide exposures and chronic kidney disease of unknown etiology: an epidemiologic review.

PubMed

Valcke, Mathieu; Levasseur, Marie-Eve; Soares da Silva, Agnes; Wesseling, Catharina

2017-05-23

The main causes of chronic kidney disease (CKD) globally are diabetes and hypertension but epidemics of chronic kidney disease of unknown etiology (CKDu) occur in Central America, Sri Lanka, India and beyond. Althoug also being observed in women, CKDu concentrates among men in agricultural sectors. Therefore, suspicions fell initially on pesticide exposure, but currently chronic heat stress and dehydration are considered key etiologic factors. Responding to persistent community and scientific concerns about the role of pesticides, we performed a systematic review of epidemiologic studies that addressed associations between any indicator of pesticide exposure and any outcome measure of CKD. Of the 21 analytical studies we identified, seven were categorized as with low, ten with medium and four with relatively high explanation value. Thirteen (62%) studies reported one or more positive associations, but four had a low explanation value and three presented equivocal results. The main limitations of both positive and negative studies were unspecific and unquantified exposure measurement ('pesticides'), the cross-sectional nature of most studies, confounding and selection bias. The four studies with stronger designs and better exposure assessment (from Sri Lanka, India and USA) all showed exposure-responses or clear associations, but for different pesticides in each study, and three of these studies were conducted in areas without CKDu epidemics. No study investigated interactions between pesticides and other concommittant exposures in agricultural occupations, in particular heat stress and dehydration. In conclusion, existing studies provide scarce evidence for an association between pesticides and regional CKDu epidemics but, given the poor pesticide exposure assessment in the majority, a role of nephrotoxic agrochemicals cannot be conclusively discarded. Future research should procure assessment of lifetime exposures to relevant specific pesticides and enough power to look into interactions with other major risk factors, in particular heat stress.

Persistent effects of prior chronic exposure to corticosterone on reward-related learning and motivation in rodents.

PubMed

Olausson, Peter; Kiraly, Drew D; Gourley, Shannon L; Taylor, Jane R

2013-02-01

Repeated or prolonged exposure to stress has profound effects on a wide spectrum of behavioral and neurobiological processes and has been associated with the pathophysiology of depression. The multifaceted nature of this disorder includes despair, anhedonia, diminished motivation, and disrupted cognition, and it has been proposed that depression is also associated with reduced reward-motivated learning. We have previously reported that prior chronic corticosterone exposure to mice produces a lasting depressive-like state that can be reversed by chronic antidepressant treatment. In the present study, we tested the effects of prior chronic exposure to corticosterone (50 μg/ml) administered to rats or to mice in drinking water for 14 days followed by dose-tapering over 9 days. The exposure to corticosterone produced lasting deficits in the acquisition of reward-related learning tested on a food-motivated instrumental task conducted 10-20 days after the last day of full dose corticosterone exposure. Rats exposed to corticosterone also displayed reduced responding on a progressive ratio schedule of reinforcement when tested on day 21 after exposure. Amitriptyline (200 mg/ml in drinking water) exposure for 14 days to mice produced the opposite effect, enhancing food-motivated instrumental acquisition and performance. Repeated treatment with amitriptyline (5 mg/kg, intraperitoneally; bid) subsequent to corticosterone exposure also prevented the corticosterone-induced deficits in rats. These results are consistent with aberrant reward-related learning and motivational processes in depressive states and provide new evidence that stress-induced neuroadaptive alterations in cortico-limbic-striatal brain circuits involved in learning and motivation may play a critical role in aspects of mood disorders.

Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

PubMed Central

2014-01-01

Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route. PMID:24684892

Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models.

PubMed

Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

2014-04-01

Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route.

Exposure to cooking oil fumes and chronic bronchitis in nonsmoking women aged 40 years and over: a health-care based study.

PubMed

Chen, Huang-Chi; Wu, Chia-Fang; Chong, Inn-Wen; Wu, Ming-Tsang

2018-02-13

Little is known about the effect of exposure to cooking oil fumes (COFs) on the development of non-malignant respiratory diseases in nonsmoking women. This study investigated the relationship between exposure to COFs and chronic bronchitis in female Taiwanese non-smokers. Searching the 1999 claims and registration records maintained by Taiwan's National Health Insurance Program, we identified 1846 women aged 40 years or older diagnosed as having chronic bronchitis (ICD-9 code: 491) at least twice in 1999 as potential study cases and 4624 women who had no diagnosis of chronic bronchitis the same year as potential study controls. We visited randomly selected women from each group in their homes, interviewed to collect related data including cooking habits and kitchen characteristics, and them a spirometry to collect FEV1 and FVC data between 2000 and 2009. After the exclusion of thirty smokers, the women were classified those with chronic bronchitis (n = 53), probable chronic bronchitis (n = 285), and no pulmonary disease (n = 306) based on physician diagnosis and American Thoracic Society criteria. Women who had cooked ≥ 21 times per week between the ages of 20 and 40 years old had a 4.73-fold higher risk of chronic bronchitis than those cooking < 14 times per week (95% CI = 1.65-13.53). Perceived kitchen smokiness was significantly associated with decreased FEV1 (- 137 ml, p = 0.021) and FEV1/FVC ratio (- 7.67%, p = 0.008). Exposure to COF may exacerbate the progression of chronic bronchitis in nonsmoking women.

Neuropsychological effects of exposure to naphtha among automotive workers.

PubMed Central

White, R F; Robins, T G; Proctor, S; Echeverria, D; Rocskay, A S

1994-01-01

The association between exposure to naphtha and neurobehavioural measures was examined prospectively over one year among workers employed at an automotive plant that used naphtha to calibrate fuel injectors. The neurobehavioural tests included those that assess mood, basic intelligence, and functioning of the cerebral frontal lobes and limbic system and were designed so that acute, reversible, and chronic effects of solvent exposure could be assessed. Participants were 248 workers in June 1988, and the testing was repeated on 185 of these workers in 1989. Concentrations of naphtha at the plant ranged from six to 709 mg/m3, although exposure was greater in 1988 than in 1989. Duration of exposure for individual subjects ranged from 0.8 to 7.3 years. Cross sectional data analyses showed significant associations between level of exposure to naphtha and slower timed scores on trails A, and greater reports of negative affective symptoms on profile of mood states scales in 1988 but not 1989. Threshold model analyses of the 1989 data showed an association between score on visual reproductions immediate recall and daily exposure to naphtha at or above 1050 h x mg/m3. Models of chronic exposure showed no associations between chronic exposure and negative neurobehavioural outcome. Results suggest that naphtha produces mild acute reversible effects on function of the central nervous system at or above daily exposures of 540 h x mg/m3 (approximately 90 ppm/h). PMID:8111457

Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice.

PubMed

Xia, Jizhou; Jin, Cuiyuan; Pan, Zihong; Sun, Liwei; Fu, Zhengwei; Jin, Yuanxiang

2018-08-01

Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that can contaminate food and water. In this study, effects of chronic exposure to low concentrations of Pb on metabolism and gut microbiota were evaluated in mice. It was observed that exposure of mice to 0.1mg/L Pb, supplied via drinking water, for 15weeks increased hepatic TG and TCH levels. The levels of some key genes related to lipid metabolism in the liver increased significantly in Pb-treated mice. For the gut microbiota, at the phylum level, the relative abundance of Firmicutes and Bacteroidetes changed obviously in the feces and the cecal contents of mice exposed to 0.1mg/L Pb for 15weeks. In addition, 16s rRNA gene sequencing further discovered that Pb exposure affected the structure and richness of the gut microbiota. Moreover, a 1 H NMR metabolic analysis unambiguously identified 31 metabolites, and 15 metabolites were noticeably altered in 0.1mg/L Pb-treated mice. Taken together, the data indicate that chronic Pb exposure induces dysbiosis of the gut microbiota and metabolic disorder in mice. Chronic Pb exposure induces metabolic disorder, dysbiosis of the gut microbiota and hepatic lipid metabolism disorder in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

Chronic Exposure to Deoxynivalenol Has No Influence on the Oral Bioavailability of Fumonisin B1 in Broiler Chickens

PubMed Central

Antonissen, Gunther; Devreese, Mathias; Van Immerseel, Filip; De Baere, Siegrid; Hessenberger, Sabine; Martel, An; Croubels, Siska

2015-01-01

Both deoxynivalenol (DON) and fumonisin B1 (FB1) are common contaminants of feed. Fumonisins (FBs) in general have a very limited oral bioavailability in healthy animals. Previous studies have demonstrated that chronic exposure to DON impairs the intestinal barrier function and integrity, by affecting the intestinal surface area and function of the tight junctions. This might influence the oral bioavailability of FB1, and possibly lead to altered toxicity of this mycotoxin. A toxicokinetic study was performed with two groups of 6 broiler chickens, which were all administered an oral bolus of 2.5 mg FBs/kg BW after three-week exposure to either uncontaminated feed (group 1) or feed contaminated with 3.12 mg DON/kg feed (group 2). No significant differences in toxicokinetic parameters of FB1 could be demonstrated between the groups. Also, no increased or decreased body exposure to FB1 was observed, since the relative oral bioavailability of FB1 after chronic DON exposure was 92.2%. PMID:25690690

THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

EPA Science Inventory

Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: VI. DEVELOPMENTAL EFFECTS.

EPA Science Inventory

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA:
VI. DEVELOPMENTAL EFFECTS

Richard K. Kwok, M.S.P.H., Judy L. Mumford, Ph.D., Pauline Mendola, Ph.D. Epidemiology and Biomarkers Branch, NHEERL, US Environmental Protection Agency; Yajua...

Exposure to Chronic Community Violence: Resilience in African American Children

ERIC Educational Resources Information Center

Jones, Janine M.

2007-01-01

In many African American communities, violence and poverty are often part of daily living. As a result, children are at risk for difficulties in all aspect of their lives, particularly their emotional well-being. This study explored the relationship between exposure to chronic community violence and the development of complex post-traumatic stress…

Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure.

PubMed

Rouas, Caroline; Souidi, Maâmar; Grandcolas, Line; Grison, Stephane; Baudelin, Cedric; Gourmelon, Patrick; Pallardy, Marc; Gueguen, Yann

2009-11-01

The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment. Copyright © 2009 Elsevier B.V. All rights reserved.

Sulfur dioxide-induced chronic bronchitis in beagle dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greene, S.A.; Wolff, R.K.; Hahn, F.F.

This study was done to produce a model of chronic bronchitis. Twelve beagle dogs were exposed to 500 ppm sulfur dioxide (SO/sub 2/) for 2 h/d, 5d/wk for 21 wk and 4 dogs were sham-exposed to filtered ambient air for the same period. Exposure effects were evaluated by periodically examining the dogs using chest radiographs, pulmonary function, tracheal mucous clearance, and the cellular and soluble components of bronchopulmonary lavage fluids. Dogs were serially sacrificed after 13 and 21 wk of exposure and after 6 and 14 wk of recovery. Clinical signs produced in the SO/sub 2/-exposed dogs included mucoid nasalmore » discharge, productive cough, moist rales on auscultation, tonsilitis, and conjunctivitis. Chest radiographs revealed mild peribronchiolar thickening. Histopathology, tracheal mucous clearance measurements, and lavage cytology were consistent with a diagnosis of chronic bronchitis. It is concluded that repeated exposure to 500 ppm SO/sub 2/ for 21 wk produced chronic bronchitis in the beagle dog. Complete recovery occurred within 5 wk following cessation of SO/sub 2/ exposure. 43 references, 2 figures, 2 tables.« less

Bilateral Vestibular Dysfunction Associated With Chronic Exposure to Military Jet Propellant Type-Eight Jet Fuel

PubMed Central

Fife, Terry D.; Robb, Michael J. A.; Steenerson, Kristen K.; Saha, Kamala C.

2018-01-01

We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3–5 years’ duration while working on or near the flight line. Exposure to toxic hydrocarbons was substantiated by the presence of JP-8 metabolite n-hexane in the blood of one of the cases. The presenting symptoms were dizziness, headache, fatigue, and imbalance. Rotational chair testing confirmed bilateral vestibular dysfunction in all the three patients. Vestibular function improved over time once the exposure was removed. Bilateral vestibular dysfunction has been associated with hydrocarbon exposure in humans, but only recently has emphasis been placed specifically on the detrimental effects of JP-8 jet fuel and its numerous hydrocarbon constituents. Data are limited on the mechanism of JP-8-induced vestibular dysfunction or ototoxicity. Early recognition of JP-8 toxicity risk, cessation of exposure, and customized vestibular therapy offer the best chance for improved balance. Bilateral vestibular impairment is under-recognized in those chronically exposed to all forms of jet fuel. PMID:29867750

Bilateral Vestibular Dysfunction Associated With Chronic Exposure to Military Jet Propellant Type-Eight Jet Fuel.

PubMed

Fife, Terry D; Robb, Michael J A; Steenerson, Kristen K; Saha, Kamala C

2018-01-01

We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3-5 years' duration while working on or near the flight line. Exposure to toxic hydrocarbons was substantiated by the presence of JP-8 metabolite n -hexane in the blood of one of the cases. The presenting symptoms were dizziness, headache, fatigue, and imbalance. Rotational chair testing confirmed bilateral vestibular dysfunction in all the three patients. Vestibular function improved over time once the exposure was removed. Bilateral vestibular dysfunction has been associated with hydrocarbon exposure in humans, but only recently has emphasis been placed specifically on the detrimental effects of JP-8 jet fuel and its numerous hydrocarbon constituents. Data are limited on the mechanism of JP-8-induced vestibular dysfunction or ototoxicity. Early recognition of JP-8 toxicity risk, cessation of exposure, and customized vestibular therapy offer the best chance for improved balance. Bilateral vestibular impairment is under-recognized in those chronically exposed to all forms of jet fuel.

Investigation of chronic toxicity of hydroxyapatite nanoparticles administered orally for one year in wistar rats.

PubMed

Remya, N S; Syama, S; Sabareeswaran, A; Mohanan, P V

2017-07-01

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (nano HA), a prospective nano biomaterial is extensively studied, its interaction on biological systems following chronic exposure is less exploited. In the present study, Wistar rats were given various concentrations of nano HA in the diet to determine the chronic toxicity and potential carcinogenicity. Altogether 140 rats were used for the study under various administration dosages along with control. The animals were sacrificed after 12months of controlled continuous dosing. All in-life parameters, including body weight, food consumption, clinical observations, survival, biochemical and hematology, were unaffected by the chronic exposure of nano HA orally. Similarly, gross and histopathological evaluation was also unchanged following exposure to nano HA. No evidence of nano HA-related lesions or Nano HA-induced neoplasia was suggested in this rodent bioassay study. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice.

PubMed

Tamura, Haruka; Ohgami, Nobutaka; Yajima, Ichiro; Iida, Machiko; Ohgami, Kyoko; Fujii, Noriko; Itabe, Hiroyuki; Kusudo, Tastuya; Yamashita, Hitoshi; Kato, Masashi

2012-01-01

We are routinely exposed to low frequency noise (LFN; below 0.5 kHz) at moderate levels of 60-70 dB sound pressure level (SPL) generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz) and high frequency noise (HFN; 16 kHz) at 70 dB SPL at a distance of approximately 10-20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance.

Risk assessment of low-level chemical exposures from consumer products under the U.S. Consumer Product Safety Commission chronic hazard guidelines.

PubMed Central

Babich, M A

1998-01-01

The U.S. Consumer Product Safety Commission (CPSC) is an independent regulatory agency that was created in 1973. The CPSC has jurisdiction over more the 15,000 types of consumer products used in and around the home or by children, except items such as food, drugs, cosmetics, medical devices, pesticides, certain radioactive materials, products that emit radiation (e.g., microwave ovens), and automobiles. The CPSC has investigated many low-level exposures from consumer products, including formaldehyde emissions from urea-formaldehyde foam insulation and pressed wood products, CO and NO2 emmissions from combustion appliances, and dioxin in paper products. Many chemical hazards are addressed under the Federal Hazardous Substances Act (FHSA), which applies to acute and chronic health effects resulting from high- or low-level exposures. In 1992 the Commission issued guidelines for assessing chronic hazards under the FHSA, including carcinogenicity, neurotoxicity, reproductive/developmental toxicity, exposure, bioavailability, risk assessment, and acceptable risk. The chronic hazard guidelines describe a series of default assumptions, which are used in the absence of evidence to the contrary. However, the guidelines are intended to be sufficiently flexible to incorporate the latest scientific information. The use of alternative procedures is permissible, on a case-by-case basis, provided that the procedures used are scientifically defensible and supported by appropriate data. The application of the chronic hazard guidelines in assessing the risks from low-level exposures is discussed. PMID:9539035

Chronic Arsenic Exposure in Nanomolar Concentrations Compromises Wound Response and Intercellular Signaling in Airway Epithelial Cells

PubMed Central

Boitano, Scott

2013-01-01

Paracrine ATP signaling in the lung epithelium participates in a variety of innate immune functions, including mucociliary clearance, bactericide production, and as an initiating signal in wound repair. We evaluated the effects of chronic low-dose arsenic relevant to U.S. drinking water standards (i.e., 10 ppb [130nM]) on airway epithelial cells. Immortalized human bronchial epithelial cells (16HBE14o-) were exposed to 0, 130, or 330nM arsenic (as Na-arsenite) for 4–5 weeks and examined for wound repair efficiency and ATP-mediated Ca2+ signaling. We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP-mediated Ca2+ signaling. We further show that arsenic compromises ATP-mediated Ca2+ signaling by altering both Ca2+ release from intracellular stores (via metabotropic P2Y receptors) and Ca2+ influx mechanisms (via ionotropic P2X receptors). To better model the effects of arsenic on ATP-mediated Ca2+ signaling under conditions of natural exposure, we cultured tracheal epithelial cells obtained from mice exposed to control or 50 ppb Na-arsenite supplemented drinking water for 4 weeks. Tracheal epithelial cells from arsenic-exposed mice displayed reduced ATP-mediated Ca2+ signaling dynamics similar to our in vitro chronic exposure. Our findings demonstrate that chronic arsenic exposure at levels that are commonly found in drinking water (i.e., 10–50 ppb) alters cellular mechanisms critical to airway innate immunity. PMID:23204110

Chronic Exposure to Low Frequency Noise at Moderate Levels Causes Impaired Balance in Mice

PubMed Central

Tamura, Haruka; Ohgami, Nobutaka; Yajima, Ichiro; Iida, Machiko; Ohgami, Kyoko; Fujii, Noriko; Itabe, Hiroyuki; Kusudo, Tastuya; Yamashita, Hitoshi; Kato, Masashi

2012-01-01

We are routinely exposed to low frequency noise (LFN; below 0.5 kHz) at moderate levels of 60–70 dB sound pressure level (SPL) generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz) and high frequency noise (HFN; 16 kHz) at 70 dB SPL at a distance of approximately 10–20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance. PMID:22768129

Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway.

PubMed

Ibarra-Lecue, Inés; Mollinedo-Gajate, Irene; Meana, J Javier; Callado, Luis F; Diez-Alarcia, Rebeca; Urigüen, Leyre

2018-04-27

Long-term use of potent cannabis during adolescence increases the risk of developing schizophrenia later in life, but to date, the mechanisms involved remain unknown. Several findings suggest that the functional selectivity of serotonin 2A receptor (5-HT2AR) through inhibitory G-proteins is involved in the molecular mechanisms responsible for psychotic symptoms. Moreover, this receptor is dysregulated in the frontal cortex of schizophrenia patients. In this context, studies involving cannabis exposure and 5-HT2AR are scarce. Here, we tested in mice the effect of an early chronic Δ 9 -tetrahydrocannabinol (THC) exposure on cortical 5-HT2AR expression, as well as on its in vivo and in vitro functionality. Long-term exposure to THC induced a pro-hallucinogenic molecular conformation of the 5-HT2AR and exacerbated schizophrenia-like responses, such as prepulse inhibition disruption. Supersensitive coupling of 5-HT2AR toward inhibitory Gαi1-, Gαi3-, Gαo-, and Gαz-proteins after chronic THC exposure was observed, without changes in the canonical Gαq/11-protein pathway. In addition, we found that inhibition of Akt/mTOR pathway by rapamycin blocks the changes in 5-HT2AR signaling pattern and the supersensitivity to schizophrenia-like effects induced by chronic THC. The present study provides the first evidence of a mechanistic explanation for the relationship between chronic cannabis exposure in early life and increased risk of developing psychosis-like behaviors in adulthood.

Effects of chronic lead intoxication on rat serotoninergic system and anxiety behavior.

PubMed

Sansar, Wafa; Bouyatas, My Mustapha; Ahboucha, Samir; Gamrani, Halima

2012-01-01

Chronic lead exposure has been shown to produce behavioral disturbances in human and animal models. These disturbances are associated with alterations in monoaminergic neurotransmission in the central nervous system (CNS), some of which have been attributed to serotonin (5-HT). This study was undertaken to investigate the chronic effects of lead exposure on the serotoninergic system in the dorsal raphe nucleus (DRN) and the consequences of its toxicity on rat behavior. Adult male Wistar rats were chronically exposed for 3 months to 0.5% lead acetate in drinking water. The serotoninergic system was evaluated using immunohistochemistry and the anxiety behavior was assessed by the light/dark box test. The results show that chronic lead exposure induces a significant increase of blood and brain lead levels in treated rats compared with controls. The density of the immunoreactive serotoninergic cell bodies was significantly higher in treated rats in all parts of the DRN. Assessment of animal behavior using the light/dark box test showed that lead-treated rats spent significantly more time in the light chamber compared with controls (P=0.001). These findings suggest that lead exposure may possibly induce increased anxiety as a consequence of changes in neuronal 5-HT content in the DRN. Copyright © 2011 Elsevier GmbH. All rights reserved.

Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

PubMed Central

Abdullah, Muhammad; Kornegay, Joe N.; Honcoop, Aubree; Parry, Traci L.; Balog-Alvarez, Cynthia J.; Muehlbauer, Michael J.; Newgard, Christopher B.; Patterson, Cam

2017-01-01

Background: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. Methods: We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Results: Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10−3), carnosine (0.40-fold of controls, p = 1.88 × 10−2), fumaric acid (0.40-fold of controls, p = 7.40 × 10−4), lactamide (0.33-fold of controls, p = 4.84 × 10−2), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10−2), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10−2), glutamic acid (2.48-fold of controls, p = 2.63 × 10−2), and proline (1.73-fold of controls, p = 3.01 × 10−2). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10−4, FDR 4.7 × 10−2), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle dysfunction. In contrast, two pathways, inosine-5′-monophosphate (VIP Score 3.91) and 3-phosphoglyceric acid (VIP Score 3.08) mainly contributed to the LDE signature, with two metabolites (phosphoglyceric acid and inosine-5′-monophosphate) being significantly decreased. When the BF and LDE were compared, the most significant metabolite was phosphoric acid, which was significantly less in the GRMD BF compared to control and GRMD LDE groups. Conclusions: The identification of elevated BF oleic acid (a long-chain fatty acid) is consistent with recent microarray studies identifying altered lipid metabolism genes, while alterations in arginine and proline metabolism are consistent with recent studies identifying elevated L-arginine in DMD patient sera as a biomarker of disease. Together, these studies demonstrate muscle-specific alterations in GRMD-affected muscle, which illustrate previously unidentified metabolic changes. PMID:28758940

Effects of chronic hypoxia on maternal vasodilation and vascular reactivity in guinea pig and ovine pregnancy.

PubMed

White, Margueritte M; Zhang, Lubo

2003-01-01

During pregnancy, exposure to chronic hypoxia is thought to be associated with an increased risk of preeclampsia and fetal intrauterine growth restriction (IUGR). While some studies suggest that this process may be mediated through effects of chronic hypoxia on uterine artery vasodilation and growth, these observations are likely to be species specific and may represent genetic variability in maternal adaptation to hypoxia. This review is a comparative analysis of the effects of chronic hypoxia on vascular reactivity in pregnant and nonpregnant guinea pig and sheep. Data suggest that exposure to chronic hypoxia is associated with enhanced uterine artery blood flow in the sheep, whereas, in the guinea pig, blood flow is decreased.

Moderators and Mediators of the Relationship Between Stress and Insomnia: Stressor Chronicity, Cognitive Intrusion, and Coping

PubMed Central

Pillai, Vivek; Roth, Thomas; Mullins, Heather M.; Drake, Christopher L.

2014-01-01

Study Objectives: To assess moderators, such as stressor chronicity, and mediators, including stress response in the form of cognitive intrusion and coping behavior, of the prospective association between naturalistic stress and incident insomnia. Design: Longitudinal. Setting: Epidemiological. Participants: A community-based sample of good sleepers (n = 2,892) with no lifetime history of insomnia. Interventions: None. Measurements and Results: Participants reported the number of stressful events they had encountered at baseline, as well as the perceived severity and chronicity of each event. Similarly, volitional stress responses such as coping, as well as more involuntary responses such as cognitive intrusion were assayed for each stressor. Follow-up assessment 1 y hence revealed an insomnia incidence rate of 9.1%. Stress exposure was a significant predictor of insomnia onset, such that the odds of developing insomnia increased by 19% for every additional stressor. Chronicity significantly moderated this relationship, such that the likelihood of developing insomnia as a result of stress exposure increased as a function of chronicity. Cognitive intrusion significantly mediated the association between stress exposure and insomnia. Finally, three specific coping behaviors also acted as mediators: behavioral disengagement, distraction, and substance use. Conclusions: Most studies characterize the relationship between stress exposure and insomnia as a simple dose-response phenomenon. However, our data suggest that certain stressor characteristics significantly moderate this association. Stress response in the form of cognitive intrusion and specific maladaptive coping behaviors mediate the effects of stress exposure. These findings highlight the need for a multidimensional approach to stress assessment in future research and clinical practice. Citation: Pillai V, Roth T, Mullins HM, Drake CL. Moderators and mediators of the relationship between stress and insomnia: stressor chronicity, cognitive intrusion, and coping. SLEEP 2014;37(7):1199-1208. PMID:25061248

Moderators and mediators of the relationship between stress and insomnia: stressor chronicity, cognitive intrusion, and coping.

PubMed

Pillai, Vivek; Roth, Thomas; Mullins, Heather M; Drake, Christopher L

2014-07-01

To assess moderators, such as stressor chronicity, and mediators, including stress response in the form of cognitive intrusion and coping behavior, of the prospective association between naturalistic stress and incident insomnia. Longitudinal. Epidemiological. A community-based sample of good sleepers (n = 2,892) with no lifetime history of insomnia. None. Participants reported the number of stressful events they had encountered at baseline, as well as the perceived severity and chronicity of each event. Similarly, volitional stress responses such as coping, as well as more involuntary responses such as cognitive intrusion were assayed for each stressor. Follow-up assessment 1 y hence revealed an insomnia incidence rate of 9.1%. Stress exposure was a significant predictor of insomnia onset, such that the odds of developing insomnia increased by 19% for every additional stressor. Chronicity significantly moderated this relationship, such that the likelihood of developing insomnia as a result of stress exposure increased as a function of chronicity. Cognitive intrusion significantly mediated the association between stress exposure and insomnia. Finally, three specific coping behaviors also acted as mediators: behavioral disengagement, distraction, and substance use. Most studies characterize the relationship between stress exposure and insomnia as a simple dose-response phenomenon. However, our data suggest that certain stressor characteristics significantly moderate this association. Stress response in the form of cognitive intrusion and specific maladaptive coping behaviors mediate the effects of stress exposure. These findings highlight the need for a multidimensional approach to stress assessment in future research and clinical practice. Pillai V, Roth T, Mullins HM, Drake CL. Moderators and mediators of the relationship between stress and insomnia: stressor chronicity, cognitive intrusion, and coping.

Termination of pseudopregnancy in the rat alters the response to progesterone, chlordiazepoxide, and MK-801 in the elevated plus-maze.

PubMed

Bitran, Daniel; Solano, Steven M

2005-07-01

Allopregnanolone, a neurosteroid-reduced metabolite of progesterone, is a well-documented positive modulator of the gamma-aminobutyric type A (GABA(A)) receptor. As has been reported for other positive modulators of the GABA(A) receptor, chronic exposure to neurosteroids is hypothesized to decrease GABA(A) receptor function. Drawing from the literature on chronic exposure to benzodiazepines or alcohol, putative changes in N-methyl-D-aspartate (NMDA) receptor function are also expected after chronic neurosteroid exposure. To assess the sensitivity of the GABA(A) and NMDA receptors after chronic elevation of neurosteroid produced by termination of pseudopregnancy in behavioral tests of anxiety and sensorimotor coordination. Female rats ovariectomized on day 10 of pseudopregnancy were tested in the elevated plus-maze and on the rotor rod after an acute injection of progesterone (4 mg/0.2 ml, s.c.), chlordiazepoxide (5 or 15 mg/kg, i.p.), or MK-801 (0.025, 0.05, or 0.1 mg/kg, i.p.). Pseudopregnancy termination produced an anxiogenic-like response in the plus-maze; an acute injection of progesterone restored baseline levels of behavior in this test. Pseudopregnancy termination eliminated the anxiolytic-like, sedative, and ataxic effects of chlordiazepoxide. In contrast, pseudopregnancy termination produced an increased sensitivity to the anxiolytic-like and ataxic effects of MK-801. The effects of pseudopregnancy termination on the behavioral response to positive modulators of the GABA(A) receptor are consistent with results from studies in which chronic exposure to neurosteroids decreases the response to acute neurosteroid and benzodiazepine administration. However, unlike the enhanced glutamatergic tone resulting from discontinuation of chronic benzodiazepine or alcohol exposure, the termination of pseudopregnancy apparently decreases NMDA receptor function.

Chronic and Acute Exposures to the World Trade Center Disaster and Lower Respiratory Symptoms: Area Residents and Workers

PubMed Central

Friedman, Stephen M.; Pillai, Parul S.; Reibman, Joan; Berger, Kenneth I.; Goldring, Roberta; Stellman, Steven D.; Farfel, Mark

2012-01-01

Objectives. We assessed associations between new-onset (post–September 11, 2001 [9/11]) lower respiratory symptoms reported on 2 surveys, administered 3 years apart, and acute and chronic 9/11-related exposures among New York City World Trade Center–area residents and workers enrolled in the World Trade Center Health Registry. Methods. World Trade Center–area residents and workers were categorized as case participants or control participants on the basis of lower respiratory symptoms reported in surveys administered 2 to 3 and 5 to 6 years after 9/11. We created composite exposure scales after principal components analyses of detailed exposure histories obtained during face-to-face interviews. We used multivariate logistic regression models to determine associations between lower respiratory symptoms and composite exposure scales. Results. Both acute and chronic exposures to the events of 9/11 were independently associated, often in a dose-dependent manner, with lower respiratory symptoms among individuals who lived and worked in the area of the World Trade Center. Conclusions. Study findings argue for detailed assessments of exposure during and after events in the future from which potentially toxic materials may be released and for rapid interventions to minimize exposures and screen for potential adverse health effects. PMID:22515865

Chronic and acute exposures to the world trade center disaster and lower respiratory symptoms: area residents and workers.

PubMed

Maslow, Carey B; Friedman, Stephen M; Pillai, Parul S; Reibman, Joan; Berger, Kenneth I; Goldring, Roberta; Stellman, Steven D; Farfel, Mark

2012-06-01

We assessed associations between new-onset (post-September 11, 2001 [9/11]) lower respiratory symptoms reported on 2 surveys, administered 3 years apart, and acute and chronic 9/11-related exposures among New York City World Trade Center-area residents and workers enrolled in the World Trade Center Health Registry. World Trade Center-area residents and workers were categorized as case participants or control participants on the basis of lower respiratory symptoms reported in surveys administered 2 to 3 and 5 to 6 years after 9/11. We created composite exposure scales after principal components analyses of detailed exposure histories obtained during face-to-face interviews. We used multivariate logistic regression models to determine associations between lower respiratory symptoms and composite exposure scales. Both acute and chronic exposures to the events of 9/11 were independently associated, often in a dose-dependent manner, with lower respiratory symptoms among individuals who lived and worked in the area of the World Trade Center. Study findings argue for detailed assessments of exposure during and after events in the future from which potentially toxic materials may be released and for rapid interventions to minimize exposures and screen for potential adverse health effects.

Occupational exposure to dust and lung disease among sheet metal workers.

PubMed Central

Hunting, K L; Welch, L S

1993-01-01

A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack-years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was significantly associated with obstructive lung disease but the dose-response relation was inconsistent, especially for those with higher pack-years of smoking exposure. Exposure to fibreglass was not a risk factor for obstructive lung disease. PMID:8507596

Chronic and persistent viral hemorrhagic septicemia virus infections in Pacific herring

USGS Publications Warehouse

Hershberger, P.K.; Gregg, J.L.; Grady, C.A.; Taylor, L.; Winton, J.R.

2010-01-01

Chronic viral hemorrhagic septicemia virus (VHSV) infections were established in a laboratory stock of Pacific herring Clupea pallasii held in a large-volume tank supplied with pathogenfree seawater at temperatures ranging from 6.8 to 11.6??C. The infections were characterized by viral persistence for extended periods and near-background levels of host mortality. Infectious virus was recovered from mortalities occurring up to 167 d post-exposure and was detected in normal-appearing herring for as long as 224 d following initial challenge. Geometric mean viral titers were generally as high as or higher in brain tissues than in pools of kidney and spleen tissues, with overall prevalence of infection being higher in the brain. Upon re-exposure to VHSV in a standard laboratory challenge, negligible mortality occurred among groups of herring that were either chronically infected or fully recovered, indicating that survival from chronic manifestations conferred protection against future disease. However, some survivors of chronic VHS infections were capable of replicating virus upon re-exposure. Demonstration of a chronic manifestation of VHSV infection among Pacific herring maintained at ambient seawater temperatures provides insights into the mechanisms by which the virus is maintained among populations of endemic hosts. ?? 2010 Inter-Research.

Chronic and persistent viral hemorrhagic septicemia virus infections in Pacific herring

USGS Publications Warehouse

Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Cortney A.; Taylor, L.

2010-01-01

Chronic viral hemorrhagic septicemia virus (VHSV) infections were established in a laboratory stock of Pacific herring Clupea pallasii held in a large-volume tank supplied with pathogen-free seawater at temperatures ranging from 6.8 to 11.6°C. The infections were characterized by viral persistence for extended periods and near-background levels of host mortality. Infectious virus was recovered from mortalities occurring up to 167 d post-exposure and was detected in normal-appearing herring for as long as 224 d following initial challenge. Geometric mean viral titers were generally as high as or higher in brain tissues than in pools of kidney and spleen tissues, with overall prevalence of infection being higher in the brain. Upon re-exposure to VHSV in a standard laboratory challenge, negligible mortality occurred among groups of herring that were either chronically infected or fully recovered, indicating that survival from chronic manifestations conferred protection against future disease. However, some survivors of chronic VHS infections were capable of replicating virus upon re-exposure. Demonstration of a chronic manifestation of VHSV infection among Pacific herring maintained at ambient seawater temperatures provides insights into the mechanisms by which the virus is maintained among populations of endemic hosts.

Comparison of short-term chronic and chronic silver toxicity to fathead minnows in unamended and sodium chloride-amended waters.

PubMed

Naddy, Rami B; Rehner, Anita B; McNerney, Gina R; Gorsuch, Joseph W; Kramer, James R; Wood, Chris M; Paquin, Paul R; Stubblefield, William A

2007-09-01

The chronic (early life stage [ELS]) and short-term chronic (STC) toxicity of silver (as silver nitrate) to fathead minnows (FHM) was determined concurrently in flow-through exposures (33 volume additions/d). Paired ELS (approximately 30 d) and STC (7 d) studies were conducted with and without the addition of 60 mg/L Cl (as NaCl). The paired studies in unamended water were later repeated using standard flow conditions (9 volume additions/d). The purpose of the paired studies was to determine if short-term chronic endpoints can be used to predict effects in ELS studies. For each experiment, a "split-chamber" design (organisms were held in a common exposure chamber) allowed the direct comparison between short-term and chronic exposures. It appeared that the chronic toxicity of silver was mitigated to some extent by NaCl addition. The maximum acceptable toxicant concentration for growth in the ELS study was 0.53 microg dissolved Ag/L under standard flow conditions. Early life stage and STC endpoints in all three studies typically agreed within a factor of two. Whole-body sodium and silver concentrations measured in individual fathead minnows during these studies showed an increase in silver body burdens and a decrease in sodium concentration. These results indicate that the STC study could be used as a surrogate test to estimate chronic toxicity and that the mechanism of chronic silver toxicity may be the same as for acute toxicity.

Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors

PubMed Central

Groneberg-Kloft, Beatrix; Kraus, Thomas; Mark, Anke van; Wagner, Ulrich; Fischer, Axel

2006-01-01

Air pollution remains a leading cause of many respiratory diseases including chronic cough. Although episodes of incidental, dramatic air pollution are relatively rare, current levels of exposure of pollutants in industrialized and developing countries such as total articles, diesel exhaust particles and common cigarette smoke may be responsible for the development of chronic cough both in children and adults. The present study analyses the effects of common environmental factors as potential causes of chronic cough. Different PubMed-based researches were performed that related the term cough to various environmental factors. There is some evidence that chronic inhalation of diesel can lead to the development of cough. For long-term exposure to nitrogen dioxide (NO2), children were found to exhibit increased incidences of chronic cough and decreased lung function parameters. Although a number of studies did not show that outdoor pollution directly causes the development of asthma, they have demonstrated that high levels pollutants and their interaction with sunlight produce ozone (O3) and that repeated exposure to it can lead to chronic cough. In summary, next to the well-known air pollutants which also include particulate matter and sulphur dioxide, a number of other indoor and outdoor pollutants have been demonstrated to cause chronic cough and therefore, environmental factors have to be taken into account as potential initiators of both adult and pediatric chronic cough. PMID:16722555

[Toxicology screening in paediatrics].

PubMed

Garcia-Algar, Óscar; Cuadrado González, Ainoha; Falcon, María

2016-09-01

The prevalence of acute or chronic exposure to substances of abuse in paediatric patients, from the neonatal period to adolescence, is not well established as most cases go unnoticed. Regardless of clinical cases of acute poisoning leading to visits to emergency room, the exposure is usually detected by a questionnaire to the parents or children. In the last few years, new validated analytical methodologies have been developed in order to detect parent drugs and their metabolites in different biological matrices. These biological matrices have different time windows for detection of the exposure: acute (i.e., urine, blood, oral fluid), and chronic (i.e., hair, meconium or teeth). The aim of this paper was to review the scenarios where the use of biological matrices is indicated for the detection of acute or chronic exposure to substances of abuse. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

PubMed

Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

2018-06-01

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

Toxic effects of lead on biochemical and histological alterations in green mussel (Perna viridis) induced by environmentally relevant concentrations.

PubMed

Hariharan, G; Purvaja, R; Ramesh, R

2014-01-01

Acute and chronic toxicity tests were conducted on green mussel (Perna viridis) to determine the adverse effects of lead (Pb). Exposure of organisms to acute toxicity test for 96 h and lethal concentration (LC(50)) was the endpoint of the test. Acute toxicity for 96-h LC(50) and 95% confidence intervals of P. viridis was 2.62 ± 0.12 (2.62-3.24) mg/L Pb. Chronic toxicity tests revealed that survival of exposed organisms decreased with elevated exposure concentrations. No-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) were calculated based on survival of test organisms. Results of this study demonstrated an increase in toxicity in test organisms with rise in exposure time and concentration. In this study, histology and biochemical enzymes, namely, catalase, reduced glutathione, glutathione S-transferase, and lipid peroxides, were correlated with chronic value and survival endpoints of P. viridis after chronic exposure to Pb. Biochemical and histological responses to different concentrations of Pb were assessed and significant differences were observed between control and increasing exposure concentrations. Biomarker studies in internal organs confirmed that the observed changes are due to adverse effects of Pb. This assessment of toxicity was the first step to determining the seawater quality criteria for marine organisms.

Acute and chronic effects of Cr(VI) on Hypsiboas pulchellus embryos and tadpoles.

PubMed

Natale, G S; Ammassari, L L; Basso, N G; Ronco, A E

2006-10-27

In the last few years there has been great concern about declines in the abundance of several species of amphibians around the world. Among amphibians, anurans have a biphasic life cycle, with aquatic tadpoles and generally terrestrial adults, and they have an extremely permeable skin, making them excellent indicators of the health of the environment. A number of different causes have been suggested for the global decline of anurans, the pollution of their habitat by chemical stressors being considered one of the major factors. Among chemical stressors, heavy metals are known for their high toxicity at very low concentrations. This study assessed short- (96 h, 'acute') and long-term (1272 h, 'chronic') exposure to Cr(VI) at lethal (3 to 90 mg 1(-1)) and sublethal concentrations (0.001 to 12 mg 1(-1)) on Hypsiboaspulchellus (previously called Hyla pulchella; see Faivovich et al. 2005) tadpoles (Fam. Hylidae) from central eastern Argentina. Fertilized eggs collected from a clean pond near La Plata (Buenos Aires Province) were used for acute and chronic toxicity testing. Assays were done under controlled laboratory conditions. Results of chronic exposure were used to assess the effect of factors such as toxicant concentration and age of organisms at the beginning of exposure on the response variables (growth, development and survival until metamorphosis). Results indicated a higher sensitivity to Cr(VI) of individuals first exposed as tadpoles than those first exposed as embryos during acute and chronic exposure. Exposure to the highest sublethal concentrations (6 to 12 mg 1(-1)) of the toxicant showed early inhibitory effects on growth of all treated organisms compensated at longer exposure periods with an increase in the growth rate compared to the control groups.

Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

PubMed

Ali, S F; Newport, G D; Scallet, A C; Paule, M G; Bailey, J R; Slikker, W

1991-11-01

THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

The physiological consequences of exposure to chronic, sublethal waterborne nickel in rainbow trout (Oncorhynchus mykiss): exercise vs resting physiology.

PubMed

Pane, Eric F; Haque, Aziz; Goss, Greg G; Wood, Chris M

2004-03-01

In rainbow trout (Oncorhynchus mykiss), following chronic (42 day) exposure to both 384 microg Ni l(-1) and 2034 microg Ni l(-1), Ni accumulation was greatest in the gill, kidney and plasma, with the plasma as the main sink for Ni. Indeed, trapped plasma analysis revealed that extensive loading of Ni in the plasma accounted for substantial percentages of accumulated Ni in several tissues including the liver and heart. Accumulated Ni in the gill and kidney was less dependent on plasma Ni concentration, suggesting a more intracellular accumulation of Ni in these tissues. We present evidence for a clear, persistent cost of acclimation to chronic, sublethal Ni exposure. Chronic (40-99 day) exposure to sublethal waterborne Ni (243-394 microg Ni l(-1); approximately 1% of the 96 h LC(50)) impaired the exercise physiology, but not the resting physiology, of rainbow trout. Ni acted as a limiting stressor, decreasing maximal rates of oxygen consumption (MO2,max) during strenuous exercise in trout exposed for 34 days to sublethal Ni. This drop in high-performance gas exchange was attributed mainly to a reduction in relative branchial diffusing capacity (D(rel)) caused by thickening of secondary lamellae. Morphometric analysis of the gills of chronically exposed fish revealed overall swelling of secondary lamellae, as well as hypertrophic respiratory epithelia within secondary lamellae. Additionally, contraction of the lamellar blood pillar system and narrowing of interlamellar water channels occurred, possibly contributing to decreased high-performance gas exchange. Decreased aerobic capacity persisted in fish previously exposed to nickel despite a clean-water exposure period of 38 days and an almost complete depuration of gill Ni, suggesting that extrabranchial mechanisms of chronic Ni toxicity may also be important. Chronic impairment of such a dynamically active and critical organ as the gill may depress the overall fitness of a fish by impairing predator avoidance, prey capture and migration success with obvious environmental implications.

The temporal impact of chronic intermittent psychosocial stress on high-fat diet-induced alterations in body weight.

PubMed

Finger, Beate C; Dinan, Timothy G; Cryan, John F

2012-06-01

Chronic stress and diet can independently or in concert influence the body's homeostasis over time. Thus, it is crucial to investigate the interplay of these parameters to gain insight into the evolution of stress-induced metabolic and eating disorders. C57BL/6J mice were subjected to chronic psychosocial (mixed model of social defeat and overcrowding) stress in combination with either a high- or low-fat diet for three or six weeks. To determine the evolution of stress and dietary effects, changes in body weight, caloric intake and caloric efficiency were determined as well as circulating leptin, insulin, glucose and corticosterone levels and social avoidance behaviour. Exposure to stress for three weeks caused an increase in weight gain, in caloric intake and in caloric efficiency only in mice on a low-fat diet. However, after six weeks, only stressed mice on a high-fat diet displayed a pronounced inhibition of body weight gain, accompanied by reduced caloric intake and caloric efficiency. Stress decreased circulating leptin levels in mice on a low-fat diet after three weeks and in mice on a high-fat diet after three and six weeks of exposure. Plasma levels of insulin and markers of insulin resistance were blunted in mice on high-fat diet following six weeks of stress exposure. Social avoidance following chronic stress was present in all mice after three and six weeks. This study describes the evolution of the chronic effects of social defeat/overcrowding stress in combination with exposure to high- or low-fat diet. Most importantly, we demonstrate that a six week chronic exposure to social defeat stress prevents the metabolic effects of high-fat diet, by inhibiting an increase in weight gain, caloric intake and efficiency and insulin resistance as well as in plasma leptin and insulin levels. This study highlights the importance of considering the chronic aspects of both parameters and their time-dependent interplay. Copyright © 2011 Elsevier Ltd. All rights reserved.

Brick mortar exposure and chronic lymphocytic leukemia.

PubMed

Markovic-Denic, L; Jankovic, S; Marinkovic, J; Radovanovic, Z

1995-01-01

A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL.

Chronic exposure to cocaine binging predisposes to an accelerated course of dilated cardiomyopathy in conscious dogs following rapid ventricular pacing.

PubMed

Parikh, Pratik; Nikolaidis, Lazaros A; Stolarski, Carol; Shen, You-Tang; Shannon, Richard P

2005-12-01

Despite extensive study, the extent to which cocaine use predisposes to cardiac injury remains unknown. We hypothesized that chronic cocaine binging would increase susceptibility to a subsequent cardiac insult, even in the absence of demonstrable effects on baseline hemodynamics. We studied progression of dilated cardiomyopathy (DCM) induced by rapid ventricular pacing (240 beats per minute) in five conscious, chronically instrumented dogs, after exposure to repetitive cocaine binging (COC) in the form of four consecutive 1 mg/kg i.v. boluses daily for 8 days, to simulate human cocaine abuse. We compared the results with nine control dogs (CON) undergoing the exact pacing protocol, without prior cocaine exposure. Baseline hemodynamics were not significantly altered by chronic cocaine exposure. Following 2 weeks of pacing, COC dogs exhibited accelerated progression to DCM, depressed plasma nitric oxide levels (CON, 17 +/- 2 microM; COC, 10 +/- 2 microM, p < 0.05), and a significantly greater increase in plasma epinephrine (CON, 33 +/- 6 pg/ml; COC, 104 +/- 24 pg/ml). After only 2 weeks of pacing, COC dogs demonstrated progressive DCM of a magnitude comparable with end-stage pacing-induced DCM. Chronic cocaine binging increases susceptibility to a subsequent myocardial insult and accelerates progression of DCM in conscious dogs following rapid pacing. These data suggest that although chronic cocaine use alone may not affect myocardial function, it predisposes to greater susceptibility to a superimposed insult.

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

PubMed

Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

2014-05-15

Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: V. BIOMARKER STUDIES - A PILOT STUDY

EPA Science Inventory

Health Effects of Chronic Exposure to Arsenic via Drinking Water in Inner Mongolia: V. Biomarker Studies - a Pilot Study

Michael T. Schmitt, M.S.P.H., Judy S. Mumford, Ph.D., National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agenc...

HEALTH RISKS FROM CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER: FINDINGS FROM THE CLINICAL INVESTIGATIONS DATA IN INNER MONGOLIA, CHINA

EPA Science Inventory

Prior studies have reported a large number of arsenicism cases in the Mongolia Autonomous Region of China due to drinking arsenic-contaminated water with concentrations up to 1.8 mg/L. However, the endemic health risks from chronic exposure to arsenic in this population have not...

Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

DTIC Science & Technology

1979-01-01

parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

GENE EXPRESSION PROFILING OF THE RAT KIDNEY FOLLOWING CHRONIC EXPOSURE (100 WKS) TO THE WATER DISINFECTANT BYPRODUCT AND RENAL CARCINOGEN, POTASSIUM BROMATE.

EPA Science Inventory

Gene expression profiling of the rat kidney following chronic exposure (100 wks) to the water
disinfectant byproduct and renal carcinogen, potassium bromate.

Don Delker, James Allen, Gail Nelson, Tanya Moore, Barbara Roop, Russell Owen, and Anthony DeAngelo. Environment...

CHRONIC EXPOSURE TO ARSENITE IN DRINKING WATER IMPAIRS GLUCOSE TOLERANCE IN C57BL/6 MICE

EPA Science Inventory

Chronic exposures to inorganic arsenic (iAs) have been associated with increased prevalence of type 2 diabetes mellitus. This study examines in vivo diabetogenic effects of iAs in an animal model. Here, weanling male C57BL/6 mice received deionized water containing iAs(III) (25 ...

Chronic dysphagia and trigeminal anesthesia after trichloroethylene exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawrence, W.H.; Partyka, E.K.

1981-12-01

A patient is described who inhaled trichloroethylene fumes while working in a closed underground pit. At the time of exposure he developed dysphagia, dysarthria and dyspnea. Assessment of his condition 11 years after the incident indicated major damage of cranial nerves, particularly the trigeminal, chronic involvement of the bulbar cranial nerves, and resultant esophageal and pharnygeal motility impairment. (JMT)

Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

ERIC Educational Resources Information Center

Hunter, John A.

2010-01-01

Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

Stress Exposure and Depression in Disadvantaged Women: The Protective Effects of Optimism and Perceived Control

ERIC Educational Resources Information Center

Grote, Nancy K.; Bledsoe, Sarah E.; Larkin, Jill; Lemay, Edward P., Jr.; Brown, Charlotte

2007-01-01

In the present study, the authors predicted that the individual protective factors of optimism and perceived control over acute and chronic stressors would buffer the relations between acute and chronic stress exposure and severity of depression, controlling for household income, in a sample of financially disadvantaged women. Ninety-seven African…

The Association Between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan.

PubMed

DeBeer, Bryann B; Davidson, Dena; Meyer, Eric C; Kimbrel, Nathan A; Gulliver, Suzy B; Morissette, Sandra B

2017-01-01

The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of chronic multisymptom illness (CMI). Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans' health is needed.

The Association between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan

PubMed Central

DeBeer, Bryann B.; Davidson, Dena; Meyer, Eric C.; Kimbrel, Nathan A.; Gulliver, Suzy B.; Morissette, Sandra B.

2017-01-01

Objective The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of Chronic Multisymptom Illness (CMI). Methods Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Results Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. Conclusions These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans’ health is needed. PMID:28045798

Urbanization and Daily Exposure to Biomass Fuel Smoke Both Contribute to Chronic Bronchitis Risk in a Population with Low Prevalence of Daily Tobacco Smoking.

PubMed

Miele, Catherine H; Jaganath, Devan; Miranda, J Jaime; Bernabe-Ortiz, Antonio; Gilman, Robert H; Johnson, Caroline M; Diette, Gregory B; Wise, Robert A; Checkley, William

2016-01-01

Risk factors beyond tobacco smoking associated with chronic bronchitis are not well understood. We sought to describe the prevalence and risk factors of chronic bronchitis across four distinct settings in Peru with overall low prevalence of tobacco smoking yet varying degrees of urbanization, daily exposure to biomass fuel smoke and living at high altitude. We analyzed data of 2,947 participants from rural and urban Puno, Lima and Tumbes including spirometry, blood samples, anthropometry and administered questionnaires about respiratory symptoms. We used multivariable Poisson regression to assess biologic, socioeconomic and environmental risk factors associated with chronic bronchitis. Overall prevalence of chronic bronchitis was 5.9% (95%CI 5.1%-6.9%) with variation by setting: prevalence was lower in semi-urban Tumbes (1.3%) vs. highly urbanized Lima (8.9%), urban Puno (7.0%) and rural Puno (7.8%; p < 0.001). Chronic bronchitis was more common among participants with vs. without COPD based on FEV1/FVC< LLN (12.1% vs 5.6%, p < 0.01) and it was associated with increased reporting of dyspnea on exertion (p < 0.001), hospitalization (p = 0.003) and workdays missed due to respiratory symptoms (p < 0.001). Older age (Prevalence ratio [PR] = 1.23 for each 10-years of age, 95%CI 1.09-1.40) past history of asthma (PR = 2.87, 95%CI 1.80-4.56), urbanization (PR = 3.34, 95%CI 2.18-5.11) and daily exposure to biomass fuel smoke (PR = 2.00, 95%CI 1.30-3.07) were all associated with chronic bronchitis. We found important variations in the prevalence of chronic bronchitis across settings. Prevalence increased with both urbanization and with daily exposure to biomass fuel smoke. Having chronic bronchitis was also associated with worse patient-centered outcomes including dyspnea, hospitalization and missed workdays.

Chronic Sinusitis

MedlinePlus

... connected to chronic sinusitis Aspirin sensitivity that causes respiratory symptoms An immune system disorder, such as HIV/AIDS or cystic fibrosis Hay fever or another allergic condition that affects your sinuses Regular exposure to pollutants such as cigarette smoke Complications Chronic ...

Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

PubMed Central

Jaén, Ángeles; Zock, Jan Paul; Kogevinas, Manolis; Ferrer, Antonio; Marín, Albert

2006-01-01

Background Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain. Methods We interviewed 576 subjects of both sexes aged 20–70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire. Forced spirometry was performed by 497 subjects according to ATS normative. Results Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women). Textile industry was the most frequently reported job in relation to these exposures (39%). Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3). Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits. Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV1 -80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV1/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed. Conclusion Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry. Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking. PMID:16476167

Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model

PubMed Central

Laube, Beth L.; Afshar-Mohajer, Nima; Koehler, Kirsten; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

2017-01-01

Objective To determine the effect of an acute (1 week) and chronic (3 weeks) exposure to E-cigarette (E-cig) emissions on mucociliary clearance (MCC) in murine lungs. Methods C57BL/6 male mice (age 10.5 ±2.4 weeks) were exposed for 20min/day to E-cigarette aerosol generated by a Joyetech 510-T® E-cig containing either 0% nicotine (N)/propylene glycol (PG) for 1 week (n = 6), or 3 weeks (n = 9), or 2.4% N/PG for one week (n = 6), or 3 weeks (n = 9), followed by measurement of MCC. Control mice (n = 15) were not exposed to PG alone, or N/PG. MCC was assessed by gamma camera following aspiration of 99mtechnetium aerosol and was expressed as the amount of radioactivity removed from both lungs over 6 hours (MCC6hrs). Venous blood was assayed for cotinine levels in control mice and in mice exposed for 3-weeks to PG alone and N/PG. Results MCC6hrs in control mice and in mice acutely exposed to PG alone and N/PG was similar, averaging (±1 standard deviation) 8.6±5.2%, 7.5±2.8% and 11.2±5.9%, respectively. In contrast, chronic exposure to PG alone stimulated MCC6hrs (17.2 ±8.0)% and this stimulation was significantly blunted following chronic exposure to N/PG (8.7 ±4.6)% (p < .05). Serum cotinine levels were <0.5ng/ml in control mice and in mice exposed to PG alone, whereas, N/PG exposed mice averaged 14.6 ± 12.0 ng/ml. Conclusions In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine. PMID:28651446

Effects of alcohol and noise on temporary threshold shift in Guinea pigs.

PubMed

Liu, Tien-Chen; Hsu, Chuan-Jen; Hwang, Juen-Haur; Tseng, Fen-Yu; Chen, Yuh-Shyang

2004-01-01

The purpose of this study was to investigate the effects of concomitant exposure to noise and alcohol on the auditory thresholds. Twenty-four guinea pigs were equally divided into three groups: the acute intoxication group, the chronic intoxication group and the control group. Animals in the acute group received single intraperitoneal injections of ethanol (2 g/kg). In the chronic group, alcohol was administered via drinking water (10%, v/v) over a 60-day period. All animals were exposed to a white noise at the intensity of 105 dB A for 30 min. Auditory brainstem response (ABR) thresholds and distortion product otoacoustic emission (DPOAE) levels were measured before, immediately after noise exposure and also 1, 2, and 7 days following exposure. The results showed: first, acute alcohol injection caused a significant, temporary elevation of ABR threshold (4.8 dB in average), while chronic alcohol treatment did not change auditory threshold significantly. Second, noise exposure induced a mean threshold shift of 15.4- 19.7 dB. ABR threshold returned to normal 2 days after exposure. Both acute and chronic alcohol treatment did not alter the magnitude and time course of recovery of the temporary threshold shift (TTS). Third, the mean DPOAE amplitudes decreased at most frequencies following acute injection of alcohol. However, the differences did not reach statistical significance. Fourth, the mean DPOAE levels dropped 3.4-9.6 dB in all groups after noise exposure and returned to normal 1 day to 2 days after noise. There were no significant differences in the amount of DPOAE suppression after noise between the three groups. In summary, we have found that acute and chronic treatment of alcohol in combination with noise did not significantly exacerbate TTS or decrease DPOAE amplitudes relative to noise exposure alone. Copyright 2004 S. Karger AG, Basel

Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations.

PubMed

Ramlan, Nurul Farhana; Sata, Nurul Syafida Asma Mohd; Hassan, Siti Norhidayah; Bakar, Noraini Abu; Ahmad, Syahida; Zulkifli, Syaizwan Zahmir; Abdullah, Che Azurahanim Che; Ibrahim, Wan Norhamidah Wan

2017-08-14

Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

PubMed

Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

2015-06-01

There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus. © The Author(s) 2015.

New Insights into the Effects of Chronic Kidney Failure and Dialysate Exposure on the Peritoneum.

PubMed

Vlahu, Carmen A; Aten, Jan; de Graaff, Marijke; van Veen, Henk; Everts, Vincent; de Waart, Dirk R; Struijk, Dirk G; Krediet, Raymond T

♦ INTRODUCTION: Chronic uremia and the exposure to dialysis solutions during peritoneal dialysis (PD) induce peritoneal alterations. Using a long-term peritoneal exposure model, we compared the effects of chronic kidney failure (CKD) itself and exposure to either a 'conventional' or a 'biocompatible' dialysis solution on peritoneal morphology and function. ♦ METHODS: Wistar rats (Harlan, Zeist, the Netherlands) were grouped into: normal kidney function (NKF), CKD induced by 70% nephrectomy, CKD receiving daily peritoneal infusions with 3.86% glucose Dianeal (CKDD), or Physioneal (both solutions from Baxter Healthcare, Castlebar, Ireland) (CKDP). At 16 weeks, a peritoneal function test was performed, and histology, ultrastructure, and hydroxyproline content of peritoneal tissue were assessed. ♦ RESULTS: Comparing CKD with NKF, peritoneal transport rates were higher, mesothelial cells (MC) displayed increased number of microvilli, blood and lymph vasculature expanded, vascular basal lamina appeared thicker, with limited areas of duplication, and fibrosis had developed. All alterations, except lymphangiogenesis, were enhanced by exposure to both dialysis fluids. Distinct MC alterations were observed in CKDD and CKDP, the latter displaying prominent basolateral protrusions. In addition, CKDP was associated with a trend towards less fibrosis compared to CKDD. ♦ CONCLUSIONS: Chronic kidney failure itself induced peritoneal alterations, which were in part augmented by exposure to glucose-based dialysis solutions. Overall, the conventional and biocompatible solutions had similar long-term effects on the peritoneum. Importantly, the latter may attenuate the development of fibrosis. Copyright © 2016 International Society for Peritoneal Dialysis.

Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization.

PubMed

Simpson, Norah S; Scott-Sutherland, Jennifer; Gautam, Shiva; Sethna, Navil; Haack, Monika

2017-09-01

Chronic pain conditions are highly co-morbid with insufficient sleep. While the mechanistic relationships between the two are not understood, chronic insufficient sleep may be one pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of three weeks of restricted sleep with limited recovery (five nights of 4-hour sleep/night followed by two nights of 8-hour sleep/night) was compared to three weeks of 8-hour sleep/night (control protocol). Seventeen healthy adults participated, with fourteen completing both three-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared to the control protocol, participants in the sleep-restriction/recovery protocol experienced mild increases in spontaneous pain (p<0.05). Heat-pain thresholds decreased following the first week of sleep restriction (p<0.05), but normalized with longer exposure to sleep restriction. In contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both p<0.05), although only in the last two weeks of the sleep restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

Influence of chronic exposure to cold environment on thyroid gland function in rabbits.

PubMed

Mustafa, S; Elgazzar, A

2014-07-01

Chronic exposure to cold can affect the thyroid gland. However, the effect on thyroid gland perfusion images and the ratio between thyroid hormones secretion were not addressed in any previous study. The present study investigates the effects of chronic cold exposure on thyroid gland function using radionuclide tracer and thyroid hormones secretion concentration. New Zealand white rabbits weighing approximately 1.8-2 kg were kept in a cold room (4°C) for 7 weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Rabbits chronically exposed to cold had less body weights than control. Thyroid gland uptake is higher in rabbits chronically exposed to cold than controls using radionuclide perfusion study. The increase was proportional to the time period, so the increase after 7 weeks was greater than 5 weeks. There is also an increase in free triiodothyronine (FT3) and a decrease in free thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher in rabbits chronically exposed to cold than control and the increase was proportional to the duration. The decrease in rabbit body weights may be related to the increase in metabolism due to the increase of thyroid hormones. Chronic cold exposure also increased the conversion of T4 to T3, which is more potent in thermogenic effect. © Georg Thieme Verlag KG Stuttgart · New York.

COPD and chronic bronchitis risk of indoor air pollution from solid fuel: a systematic review and meta-analysis.

PubMed

Kurmi, Om P; Semple, Sean; Simkhada, Padam; Smith, W Cairns S; Ayres, Jon G

2010-03-01

Over half the world is exposed daily to the smoke from combustion of solid fuels. Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease and can be caused by biomass smoke exposure. However, studies of biomass exposure and COPD show a wide range of effect sizes. The aim of this systematic review was to quantify the impact of biomass smoke on the development of COPD and define reasons for differences in the reported effect sizes. A systematic review was conducted of studies with sufficient statistical power to calculate the health risk of COPD from the use of solid fuel, which followed standardised criteria for the diagnosis of COPD and which dealt with confounding factors. The results were pooled by fuel type and country to produce summary estimates using a random effects model. Publication bias was also estimated. There were positive associations between the use of solid fuels and COPD (OR=2.80, 95% CI 1.85 to 4.0) and chronic bronchitis (OR=2.32, 95% CI 1.92 to 2.80). Pooled estimates for different types of fuel show that exposure to wood smoke while performing domestic work presents a greater risk of development of COPD and chronic bronchitis than other fuels. Despite heterogeneity across the selected studies, exposure to solid fuel smoke is consistently associated with COPD and chronic bronchitis. Efforts should be made to reduce exposure to solid fuel by using either cleaner fuel or relatively cleaner technology while performing domestic work.

Chronic exposure of grandparents to poverty and body mass index trajectories of grandchildren: a prospective intergenerational study.

PubMed

Li, Miao

2015-02-01

In this study, I used the growth curve model to examine the association between grandparents' (first generation (G1)) life-course exposure to chronic poverty and grandchildren's (third generation (G3)) body mass index (BMI; weight (kg)/height (m)(2)) growth trajectories. This association was estimated separately for male and female grandchildren. Analyses were based on prospective data from a US longitudinal survey, the Panel Study of Income Dynamics (1968-2011), and 2 of its supplemental studies: the Child Development Supplement (1997-2011) and the Transition into Adulthood Study (1997-2011). A prospectively enrolled nationally representative cohort of 2,613 G3 youth (1,323 male, 1,290 female) sampled in the 2 supplemental studies was linked to 1,719 grandparents from the Panel Study of Income Dynamics core sample. Chronic exposure to poverty among grandparents was prospectively ascertained annually over a 30-year period prior to the collection of data on grandchildren. Findings suggested that grandparents' chronic poverty exposure was positively associated with the slope of the BMI trajectory among granddaughters (β = 0.10, 95% confidence interval: 0.03, 0.17) but not among grandsons (β = 0.02, 95% confidence interval: -0.04, 0.08). The association between grandparents' chronic poverty exposure and granddaughters' BMI growth slope remained even after controlling for parental (second generation (G2)) socioeconomic status and BMI. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Incidence and prevalence of chronic bronchitis: impact of smoking and welding. The RHINE study.

PubMed

Holm, M; Kim, J-L; Lillienberg, L; Storaas, T; Jögi, R; Svanes, C; Schlünssen, V; Forsberg, B; Gíslason, T; Janson, C; Torén, K

2012-04-01

To investigate the prevalence and incidence rate of chronic bronchitis (CB) in relation to smoking habits and exposure to welding fumes in a general population sample. Subjects from Northern Europe born between 1945 and 1971 who participated in Stage 1 (1989-1994) of the European Community Respiratory Health Survey were mailed a respiratory questionnaire in 1999-2001 (the RHINE study); 15,909 answered the questionnaire and gave complete data on smoking. CB was defined as chronic productive cough of at least 3 months a year for 2 consecutive years. The questionnaire comprised an item about age when CB started and items about exposure to welding fumes. The incidence of CB was retrospectively assessed for the observation period 1980-2001. CB had a prevalence of 5.4%, and was associated with current smoking and welding exposure. The incidence rate of CB was 1.9 per 1000 person-years, and was increased in relation to welding exposure (low exposure HR 1.4, 95%CI 1.1-1.8; high exposure HR 2.0, 95%CI 1.6-2.7) and in relation to smoking (HR 2.1, 95%CI 1.8-2.5). Smoking and occupational exposure to welding fumes are both associated with an increased risk of CB.

DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

PubMed Central

Musilli, S.; Nicolas, N.; El Ali, Z.; Orellana-Moreno, P.; Grand, C.; Tack, K.; Kerdine-Römer, S.; Bertho, J. M.

2017-01-01

90Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL−1 of 90Sr. Results indicated that a 30-minute exposure to 90Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90Sr exposure. PMID:28134299

DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences.

PubMed

Musilli, S; Nicolas, N; El Ali, Z; Orellana-Moreno, P; Grand, C; Tack, K; Kerdine-Römer, S; Bertho, J M

2017-01-30

90 Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90 Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90 Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90 Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL -1 of 90 Sr. Results indicated that a 30-minute exposure to 90 Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90 Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90 Sr exposure.

Development of the larval amphibian growth and development assay: Effects of chronic 4-tert-octylphenol or 17ß-trenbolone exposure in Xenopus laevis from embryo to juvenile

EPA Science Inventory

The Larval Amphibian Growth and Development Assay (LAGDA) is a Tier II test guideline being developed by the US Environmental Protection Agency under the Endocrine Disruptor Screening Program. The LAGDA was designed to evaluate effects of chronic chemical exposure on growth, thy...

Differences in Depression, Posttraumatic Stress Disorder, and Lifetime Trauma Exposure in Formerly Abused Women with Mild versus Moderate to Severe Chronic Pain

ERIC Educational Resources Information Center

Humphreys, Janice; Cooper, Bruce A.; Miaskowski, Christine

2010-01-01

Although associations between intimate partner violence, chronic pain, depression, posttraumatic stress disorder (PTSD), and lifetime trauma exposure are well known, previous studies are limited by their recruitment of women from shelters. These relationships were explored with a community-based sample of formerly abused women ( N = 84).…

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: IV. DISTRIBUTION OF ARSENIC CONCENTRATIONS IN WELLS

EPA Science Inventory

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA:
IV. DISTRIBUTION OF ARSENIC CONCENTRATIONS IN WELLS

Zhixiong Ning, B.S., Zhiyi Liu,B.S., Shiying Zhang, B.S., Chenglong Ma, B.S., Inner Mongolia Ba Men Anti-epidemic Station, Michael Ri...

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA. III. NEUROLOGICAL SYMPTOMS AND PIN-PRICK MEASURES

EPA Science Inventory

Health Effects of Chronic Exposure to Arsenic via Drinking Water in Inner Mongolia: III. Neurological Symptoms and Pin-prick Measures

Yanhong Li, M.D.,Yajuan.Xia, M.D., Kegong Wu, M.D., Inner Mongolia Center For Endemic Disease Control and Research, Ling Ling He, B.S., Zhi...

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: II. VIBROTACTILE AND VISUAL MEASURES FINAL DOCUMENT TITLE.

EPA Science Inventory

HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC IN DRINKING WATER IN INNER MONGOLIA: II. VIBROTACTILE AND VISUAL MEASURES.

David Otto, Ph.D., Judy Mumford, Ph.D., Richard Kwok, M.S.P.H., Ken Hudnell, Ph.D.,
U.S. Environmental Protection Agency; Yanhong Li, M.D., Yajuan ...

The Effect of Chronic Hypercapnia on Oxygen Affinity and 2, 3 Diphosphoglycerate as Related to Submarine Exposure

DTIC Science & Technology

The relationship between oxygen affinity and 2,3 diphosphoglycerate (2,3 DPG) in the red cell has been studied in chronic hypercapnia induced by...initial values after seven days of exposure. Both oxygen half-saturation pressure (P50) and the level of 2,3 DPG of the red cells followed the time

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

PubMed

Solanki, Hitendra S; Advani, Jayshree; Khan, Aafaque Ahmad; Radhakrishnan, Aneesha; Sahasrabuddhe, Nandini A; Pinto, Sneha M; Chang, Xiaofei; Prasad, Thottethodi Subrahmanya Keshava; Mathur, Premendu Prakash; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi

2017-08-01

Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.

Smoking, environmental tobacco smoke and occupational irritants increase the risk of chronic rhinitis.

PubMed

Hisinger-Mölkänen, Hanna; Piirilä, Päivi; Haahtela, Tari; Sovijärvi, Anssi; Pallasaho, Paula

2018-01-01

Allergic and non-allergic rhinitis cause a lot of symptoms in everyday life. To decrease the burden more information of the preventable risk factors is needed. We assessed prevalence and risk factors for chronic nasal symptoms, exploring the effects of smoking, environmental tobacco smoke, exposure to occupational irritants, and their combinations. In 2016, a postal survey was conducted among a random population sample of 8000 adults in Helsinki, Finland with a 50.5% response rate. Smoking was associated with a significant increase in occurrence of chronic rhinitis (longstanding nasal congestion or runny nose), but not with self-reported or physician diagnosed allergic rhinitis. The highest prevalence estimates of nasal symptoms, 55.1% for chronic rhinitis, 49.1% for nasal congestion, and 40.7% for runny nose, were found among smokers with occupational exposure to gases, fumes or dusts.Besides active smoking, also exposure to environmental tobacco smoke combined with occupational exposure increased the risk of nasal symptoms. Smoking, environmental tobacco smoke, and occupational irritants are significant risk factors for nasal symptoms with an additive pattern. The findings suggest that these factors should be systematically inquired in patients with nasal symptoms for appropriate preventive measures. (192 words).

Cigarette smoke induces mitochondrial metabolic reprogramming in lung cells.

PubMed

Solanki, Hitendra S; Babu, Niraj; Jain, Ankit P; Bhat, Mohd Younis; Puttamallesh, Vinuth N; Advani, Jayshree; Raja, Remya; Mangalaparthi, Kiran K; Kumar, Mahesh M; Prasad, T S Keshava; Mathur, Premendu Prakash; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi

2018-05-01

Cellular transformation owing to cigarette smoking is due to chronic exposure and not acute. However, systematic studies to understand the molecular alterations in lung cells due to cigarette smoke are lacking. To understand these molecular alterations induced by chronic cigarette smoke exposure, we carried out tandem mass tag (TMT) based temporal proteomic profiling of lung cells exposed to cigarette smoke for upto 12months. We identified 2620 proteins in total, of which 671 proteins were differentially expressed (1.5-fold) after 12months of exposure. Prolonged exposure of lung cells to smoke for 12months revealed dysregulation of oxidative phosphorylation and overexpression of enzymes involved in TCA cycle. In addition, we also observed overexpression of enzymes involved in glutamine metabolism, fatty acid degradation and lactate synthesis. This could possibly explain the availability of alternative source of carbon to TCA cycle apart from glycolytic pyruvate. Our data indicates that chronic exposure to cigarette smoke induces mitochondrial metabolic reprogramming in cells to support growth and survival. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

APPROACHES TO RISK ASSESSMENT FOR MULTIPLE CHEMICAL EXPOSURES

EPA Science Inventory

The Environmental Criteria and Assessment Office (ECAO) in Cincinnati has developed health risk assessment methods for chronic exposure to single chemical from a single route of exposure. Risk assessments for carcinogens associated an exposure level with a particular incidence of...

Chronic Noise Exposure Acts Cumulatively to Exacerbate Alzheimer’s Disease-Like Amyloid-β Pathology and Neuroinflammation in the Rat Hippocampus

PubMed Central

Cui, Bo; Li, Kang; Gai, Zhihui; She, Xiaojun; Zhang, Na; Xu, Chuanxiang; Chen, Xuewei; An, Gaihong; Ma, Qiang; Wang, Rui

2015-01-01

A putative etiological association exists between noise exposure and Alzheimer’s disease (AD). Amyloid-β (Aβ) pathology is thought to be one of the primary initiating factors in AD. It has been further suggested that subsequent dysregulation of Aβ may play a mechanistic role in the AD-like pathophysiology associated with noise exposure. Here, we used ELISA, immunoblotting, cytokine arrays, and RT-PCR, to examine both hippocampal Aβ pathology and neuroinflammation in rats at different time points after noise exposure. We found that chronic noise exposure significantly accelerated the progressive overproduction of Aβ, which persisted for 7 to 14 days after the cessation of exposure. This effect was accompanied by up-regulated expression of amyloid precursor protein (APP) and its cleavage enzymes, β- and γ-secretases. Cytokine analysis revealed that chronic noise exposure increased levels of tumor necrosis factor-α and the receptor for advanced glycation end products, while decreasing the expression of activin A and platelet-derived growth factor- AA. Furthermore, we found persistent elevations of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 expression that closely corresponded to the noise-induced increases in Aβ and neuroinflammation. These studies suggest that lifelong environmental noise exposure may have cumulative effects on the onset and development of AD. PMID:26251361

Neovascularization and Angiogenic Gene Expression Following Chronic Arsenic Exposure in Mice

PubMed Central

Soucy, Nicole V.; Mayka, Debra; Klei, Linda R.; Nemec, Antonia A.; Bauer, John A.; Barchowsky, Aaron

2015-01-01

Exposure to arsenic in drinking water increases incidence of cardiovascular diseases. However, the basic mechanisms and genetic changes that promote these diseases are unknown. This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5–500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50–250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel density were reduced by exposure to 500 ppb AsIII for 20 wk. These data demonstrate differential concentration and time-dependent effects of chronic arsenic exposure on cardiovascular phenotype and vascular remodeling that may explain the etiology for AsIII-induced disease. PMID:15738583

Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease.

PubMed

Eisner, Mark D; Balmes, John; Katz, Patricia P; Trupin, Laura; Yelin, Edward H; Blanc, Paul D

2005-05-12

Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction. Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies. Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD. Participants were recruited from all 48 contiguous U.S. states by random digit dialing. Lifetime ETS exposure was ascertained by structured telephone interview. We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD. Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD. The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21). The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84). The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure. ETS exposure may be an important cause of COPD. Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure.

Burn Pit Emissions Exposure and Respiratory and Cardiovascular Conditions Among Airborne Hazards and Open Burn Pit Registry Participants.

PubMed

Liu, Jason; Lezama, Nicholas; Gasper, Joseph; Kawata, Jennifer; Morley, Sybil; Helmer, Drew; Ciminera, Paul

2016-07-01

The aim of this study was to determine how burn pit emissions exposure is associated with the incidence of respiratory and cardiovascular conditions. We examined the associations between assumed geographic and self-reported burn pit emissions exposure and respiratory and cardiovascular outcomes in participants of the Airborne Hazards and Open Burn Pit Registry. We found significant dose-response associations for higher risk of self-reported emphysema, chronic bronchitis, or chronic obstructive pulmonary disease with increased days of deployment within 2 miles of selected burn pits (P-trend = 0.01) and self-reported burn pit smoke exposure (P-trend = 0.0005). We found associations between burn pit emissions exposure and higher incidence of post-deployment self-reported respiratory and cardiovascular conditions, but these findings should be interpreted with caution because the surrogate measurements of burn pit emissions exposure in this analysis may not reflect individual exposure levels.

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

PubMed Central

Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D’Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

2017-01-01

Background Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. Methods To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. Results LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. Conclusions We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function. PMID:28052095

Does chronic exposure to mobile phones affect cognition?

PubMed Central

Mohan, Mamta; Khaliq, Farah; Panwar, Aprajita; Vaney, Neelam

2016-01-01

Summary Mobile phones form an integral part of our modern lifestyle. Following the drastic rise in mobile phone use in recent years, it has become important to study its potential public health impact. Amongst the various mobile phone health hazards, the most alarming is the possible effect on the brain. The aim of the present study was to explore whether chronic exposure to mobile phones affects cognition. Ninety subjects aged 17–25 years with normal hearing were recruited for the study and divided into three groups according to their duration of mobile phone use. No significant differences in N100, P200, N200, P300 latencies or N2-P300 amplitude were observed. Our results suggest that chronic mobile phone exposure does not have detrimental effects on cognition. PMID:27027894

Chronic Sucralose or L-Glucose Ingestion Does Not Suppress Food Intake.

PubMed

Wang, Qiao-Ping; Simpson, Stephen J; Herzog, Herbert; Neely, G Gregory

2017-08-01

Despite widespread consumption of non-nutritive sweeteners (NNSs), the impact of manipulating the perceived sweetness of food is unclear. Previously we reported that chronic consumption of the NNSs sucralose or L-glucose led to increased calories consumed post-exposure; however, a recent study suggested this effect occurs because NNSs acutely suppress food intake, leading to a caloric debt. Here we show that acute ingestion of sucralose in the context of a low-carbohydrate diet causes a pronounced increase in calories consumed. Moreover, neither sucralose nor L-glucose had a lasting effect on food intake during chronic exposure; however, both NNSs enhance food intake post-exposure. Together these data confirm that sucralose and L-glucose promote food intake under a variety of experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Epigenetic programming of obesity and diabetes by in utero exposure to gestational diabetes mellitus.

PubMed

Ruchat, Stephanie-May; Hivert, Marie-France; Bouchard, Luigi

2013-10-01

It is now well accepted that offspring exposed to maternal undernutrition, obesity, or gestational diabetes mellitus have an increased risk for chronic diseases later in life, supporting the theory of the early origins of chronic diseases. However, the molecular mechanisms through which the exposure to an altered in utero environment translates into the development of chronic diseases are not yet well understood. Recently reported promising results help to resolve this issue. They suggest that epigenetic modifications are a potential mechanism for fetal metabolic programming. This review provides an overview of the relationship between the exposure to an altered intrauterine environment and fetal metabolic programming, focusing on gestational diabetes mellitus and epigenetic variations at adipokine candidate genes. © 2013 International Life Sciences Institute.

Effect of Schizandra chinensis lignans on cell division in the corneal epithelium and tongue of albino rats exposed to chronic cold stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mel'nik, E.I.; Lupandin, A.V.; Timoshin, S.S.

The authors study the possibility of correcting cellular manifestations of disadaptation following chronic exposure to cold stress by means of preparations of Sch. chinensis. The model of chronic stress was cooling male albino rats daily for 1.5 h to a temperature of 28-30 C for 28 days. Since differences between levels of proliferation in intact animals and in the rats receiving 1.9% ethanol solution were absent, values obtained in the group of intact animals are presented in a table as the control. The animals underwent euthanasia 48 hours after the final exposure to the cold. The rats received an injectionmore » of tritium-thymidine one hour before sacrifice. It is shown that the results confirm those in previous studies of stimulation of DNA synthesis and mitotic activity in the corneal and lingual epithelium of albino rats during chronic exposure to stress.« less

[Blastomogenic effect following single and chronic exposure to a mixture of cesium-137 and strontium-90].

PubMed

Danetskaia, E V; Lavrent'ev, L N; Zapol'skaia, N A

1976-01-01

The rate of tumor incidence in different rhythms of rat stomach exposure to cesium-137 and strontium-90 was analysed. The correlative values of the administered nucleids activity were selected by analogy with their content in global natural fall-out. In single exposure to the concentrations of 400 and 100 mc/per rat of cesium-137 and strontium-90 mixture accordingly, osteogenic osteosarcomas developed approximatley 4 times as frequently as in chronic administration of the same radionucleids in concentrations of 2 and 8 mc/per rat, correspondingly.

Long term exposure to environmental concentrations of diesel exhaust particles does not impact the phenotype of human bronchial epithelial cells.

PubMed

Savary, Camille C; Bellamri, Nessrine; Morzadec, Claudie; Langouët, Sophie; Lecureur, Valérie; Vernhet, Laurent

2018-06-19

Chronic exposure to diesel engine exhausts is associated with an increased risk of pulmonary diseases including lung cancer. Diesel engine exhausts contain large amounts of diesel exhaust particles (DEP) on which are adsorbed several carcinogenic compounds such as polycyclic aromatic hydrocarbons. Acute toxicity of high concentrations of DEP has been largely demonstrated in various in vitro cellular models. In contrast, the cellular and molecular impacts of low environmental concentrations of DEP on the phenotype of chronically exposed lung epithelial cells remain to be investigated. In the present study, we show that long term exposure (6 months) to 2 μg/ml (0.4 μg/cm 2 ) DEP (standard reference material 1650b) increased cytochrome P4501A mRNA levels in the human bronchial epithelial BEAS-2B cell line. However, chronic exposure to DEP did not change cell morphology, trigger epithelial-mesenchymal transition or increase anchorage-independent cell growth. Moreover, DEP increase neither the levels of reactive oxygen species or those of γ-histone H2AX, nor the expression of interleukin-6 and interleukin-8. Our results thus demonstrate that the chronic exposure to low DEP concentrations could increase cytochrome P501A gene expression in BEAS-2B cells but did not induce molecular effects related to genotoxicity, oxidative stress or inflammation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronic Δ⁸-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain.

PubMed

Prini, Pamela; Penna, Federica; Sciuccati, Emanuele; Alberio, Tiziana; Rubino, Tiziana

2017-10-04

Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ⁸-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ⁸-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ⁸-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ⁸-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ⁸-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ⁸-THC adverse effects.

Chronic and Acute Ozone Exposure in the Week Prior to Delivery Is Associated with the Risk of Stillbirth

PubMed Central

Ha, Sandie; Pollack, Anna Z.; Zhu, Yeyi; Seeni, Indulaxmi; Kim, Sung Soo; Sherman, Seth; Liu, Danping

2017-01-01

Chronic and acute air pollution has been studied in relation to stillbirth with inconsistent findings. We examined stillbirth risk in a retrospective cohort of 223,375 singleton deliveries from 12 clinical sites across the United States. Average criteria air pollutant exposure was calculated using modified Community Multiscale Air Quality models for the day of delivery and each of the seven days prior, whole pregnancy, and first trimester. Poisson regression models using generalized estimating equations estimated the relative risk (RR) of stillbirth and 95% confidence intervals (CI) in relation to an interquartile range increase in pollutant with adjustment for temperature, clinical, and demographic factors. Ozone (O3) was associated with a 13–22% increased risk of stillbirth on days 2, 3, and 5–7 prior to delivery in single pollutant models, and these findings persisted in multi-pollutant models for days 5 (RR = 1.22, CI = 1.07–1.38) and 6 (RR = 1.18, CI = 1.04–1.33). Whole pregnancy and first trimester O3 increased risk 18–39% in single pollutant models. Maternal asthma increased stillbirth risk associated with chronic PM2.5 and carbon monoxide exposures. Both chronic and acute O3 exposure consistently increased stillbirth risk, while the role of other pollutants varied. Approximately 8000 stillbirths per year in the US may be attributable to O3 exposure. PMID:28684711

Effects of a chronic exposure to a highly palatable diet and its withdrawal, in adulthood, on cerebral Na+,K+-ATPase and plasma S100B in neonatally handled rats.

PubMed

da S Benetti, Carla; Silveira, Patrícia P; Matté, Cristiane; Stefanello, Francieli M; Leite, Marina C; Gonçalves, Carlos Alberto S; Wyse, Angela T S; Dalmaz, Carla; Goldani, Marcelo Z

2010-04-01

We have previously demonstrated that early environment influences the metabolic response, affecting abdominal fat deposition in adult female rats exposed to a long-term highly caloric diet. In the present study, our goal was to verify the effects of the chronic exposure, in adulthood, to a highly palatable diet (chocolate) on cerebral Na+,K+-ATPase activity and S100B protein concentrations, and the response to its withdrawal in neonatally handled and non-handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, S100B protein concentrations, as well as cerebral Na(+),K(+)-ATPase activity during chronic exposure and after chocolate withdrawal in adult female rats that had been exposed or not to neonatal handling (10 min/day, 10 first days of life). Non-handled rats chronically exposed to chocolate exhibited increased plasma S100B levels, but there was no difference in abdominal fat S100B concentration between groups. Chronic chocolate consumption decreased Na+,K+-ATPase activity in both amygdala and hippocampus in non-handled, but not in handled rats, and this effect disappeared after chocolate withdrawal. Non-handled animals also demonstrated increased frequency of head shaking in the open field after 24h of chocolate withdrawal in comparison to handled ones. These findings suggest that neonatal handling modifies the vulnerability to metabolic and brain alterations induced by chronic exposure to a highly palatable diet in adulthood. Copyright 2009 ISDN. Published by Elsevier Ltd. All rights reserved.

Behavioral effects of D3 receptor inhibition and 5-HT4 receptor activation on animals undergoing chronic cannabinoid exposure during adolescence.

PubMed

Abboussi, Oualid; Said, Nadia; Fifel, Karim; Lakehayli, Sara; Tazi, Abdelouahhab; El Ganouni, Soumaya

2016-04-01

Chronic exposure to cannabinoids during adolescence results in long-lasting behavioral deficits that match some symptomatologic aspects of schizophrenia. The aim of this study was to investigate the reversibility of the emotional and the cognitive effects of chronic exposure to cannabinoids during adolescence, via subsequent modulation of the serotoninergic 5-HT4 and dopaminergic D3 receptors. RS67333 as a 5-HT4 agonist and U-99194A as a D3 antagonist were administered separately at 1 mg/kg and 20 mg/kg, and in combination at 0.5 mg/kg and 10 mg/kg to adult animals undergoing chronic treatment with the synthetic cannabinoid receptor agonist WIN55,212-2 (1 mg/kg) during adolescence. Animals were tested for anxiety-like behavior and episodic-like memory in the open field and novel object recognition tests respectively 30 minutes after the last drug administration. Chronic WIN55,212-2 treated animals exhibited a lasting disruption of episodic memory and increased anxiety levels. The effect on episodic-like memory were partially restored by acute administration of RS67333 and U-99194A and completely by administration of both drugs in combination at lower doses. However, only RS67333 (20 mg/kg) improved the anxiogenic-like effect of WIN55,212-2. These findings give further support that chronic exposure to cannabinoids during adolescence may be used as an animal model for schizophrenia, and highlight D3 and 5-HT4 receptors as potential targets for an enhanced treatment of the cognitive aspect of this disease.

Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1α Expression and Regulated By microRNA-23a.

PubMed

Chen, Xiaoming; Liu, Xinqin; Li, Bin; Zhang, Qian; Wang, Jiye; Zhang, Wenbin; Luo, Wenjing; Chen, Jingyuan

2017-01-01

Background: Neuron apoptosis mediated by hypoxia inducible factor 1α (HIF-1α) in hippocampus is one of the most important factors accounting for the chronic hypobaric hypoxia induced cognitive impairment. As a neuroprotective molecule that is up-regulated in response to various environmental stress, CIRBP was reported to crosstalk with HIF-1α under cellular stress. However, its function under chronic hypobaric hypoxia remains unknown. Objective: In this study, we tried to identify the role of CIRBP in HIF-1α mediated neuron apoptosis under chronic hypobaric hypoxia and find a possible method to maintain its potential neuroprotective in long-term high altitude environmental exposure. Methods: We established a chronic hypobaric hypoxia rat model as well as a tissue culture model where SH-SY5Y cells were exposed to 1% hypoxia. Based on these models, we measured the expressions of HIF-1α and CIRBP under hypoxia exposure and examined the apoptosis of neurons by TUNEL immunofluorescence staining and western blot analysis of apoptosis related proteins. In addition, by establishing HIF-1α shRNA and pEGFP-CIRBP plasmid transfected cells, we confirmed the role of HIF-1α in chronic hypoxia induced neuron apoptosis and identified the influence of CIRBP over-expression upon HIF-1α and neuron apoptosis in the process of exposure. Furthermore, we measured the expression of the reported hypoxia related miRNAs in both models and the influence of miRNAs' over-expression/knock-down upon CIRBP in the process of HIF-1α mediated neuron apoptosis. Results: HIF-1α expression as well as neuron apoptosis was significantly elevated by chronic hypobaric hypoxia both in vivo and in vitro . CIRBP was induced in the early stage of exposure (3d/7d); however as the exposure was prolonged (21d), CIRBP level of the hypoxia group became significantly lower than that of control. In addition, HIF-1α knockdown significantly decreased neuron apoptosis under hypoxia, suggesting HIF-1α may be pro-apoptotic in the process of exposure. CIRBP over-expression significantly suppressed HIF-1α up-regulation in hypoxia and inhibited HIF-1α mediated neuron apoptosis. Interestingly, miR-23a was also induced by hypoxia exposure and showed the same changing tendency with CIRBP (increasing in 3d/7d, decreasing in 21d). In addition, over-expressing miR-23a up-regulated CIRBP, down-regulated HIF-1α and attenuated neuron apoptosis. Conclusion: Cold inducible RNA binding protein is involved in chronic hypoxia induced neuron apoptosis by down-regulating HIF-1α expression, and MiR-23a may be an important tool to maintain CIRBP level and function.

Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

PubMed Central

Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

2016-01-01

Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and may represent a treatable underlying disease etiology in a subset of genetically susceptible patients with RUC, CFS, and other immune disorders. PMID:27165859

Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

PubMed Central

Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

2016-01-01

Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:28239613

Injury, intense dust exposure, and chronic disease among survivors of the World Trade Center terrorist attacks of September 11, 2001.

PubMed

Alper, Howard E; Yu, Shengchao; Stellman, Steven D; Brackbill, Robert M

2017-12-01

The World Trade Center attack of September 11, 2001 in New York City (9/11) exposed thousands of people to intense concentrations of hazardous materials that have resulted in reports of increased levels of asthma, heart disease, diabetes, and other chronic diseases along with psychological illnesses such as post-traumatic stress disorder (PTSD). Few studies have discriminated between health consequences of immediate (short-term or acute) intense exposures versus chronic residential or workplace exposures. We used proportional hazards methods to determine adjusted hazard ratios (AHRs) for associations between several components of acute exposures (e.g., injury, immersion in the dust cloud) and four chronic disease outcomes: asthma, other non-neoplastic lung diseases, cardiovascular disease, and diabetes, in 8701 persons free of those conditions prior to exposure and who were physically present during or immediately after the World Trade Center attacks. Participants were followed prospectively up to 11 years post-9/11. Heart disease exhibited a dose-response association with sustaining injury (1 injury type: AHR =2.0, 95% CI (Confidence Interval) 1.1-3.6; 2 injury types: AHR = 3.1, 95% CI 1.2-7.9; 3 or more injury types: AHR = 6.8, 95% CI 2.0-22.6), while asthma and other lung diseases were both significantly associated with dust cloud exposure (AHR = 1.3, 95% CI 1.0-1.6). Diabetes was not associated with any of the predictors assessed in this study. In this study we demonstrated that the acute exposures of injury and dust cloud that were sustained on 9/11/2001 had significant associations with later heart and respiratory diseases. Continued monitoring of 9/11 exposed persons' health by medical providers is warranted for the foreseeable future.

Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh.

PubMed

Islam, Rafiqul; Khan, Ismail; Hassan, Sheikh Nazmul; McEvoy, Mark; D'Este, Catherine; Attia, John; Peel, Roseanne; Sultana, Munira; Akter, Shahnaz; Milton, Abul Hasnat

2012-06-07

Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.

Association between type 2 diabetes and chronic arsenic exposure in drinking water: A cross sectional study in Bangladesh

PubMed Central

2012-01-01

Background Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. Methods This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. Results A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose–response pattern was also observed. Conclusions These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years. PMID:22676249

Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Ping; Koenig, Rolf; Boor, Paul J.

2008-04-01

Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltrationmore » was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice.« less

Effects of Long-Term Dust Exposure on Human Respiratory System Health in Minqin County, China.

PubMed

Wang, Jinyu; Li, Sheng; Wang, Shigong; Shang, Kezheng

2015-01-01

The aim of this study was to assess the effects of long-term sand dust exposure on human respiratory health. Dust events break out frequently in Minqin County, northwest China, whereas Pingliang City, northwest China, is rarely influenced by dust events. Therefore, Minqin and Pingliang were selected as sand dust exposure region and control area, respectively. The incidence of respiratory system diseases and symptoms was determined through a structured respiratory health questionnaire (ATS-DLD-78-A) and personal interviews. The subjects comprised 728 farmers (Minqin, 424; Pingliang, 304) aged 40 years or older, who had nondocumented occupational history to industrial dust exposure. Prevalences (odds ratio [OR], 95% confidence interval [CI]) of chronic rhinitis, chronic bronchitis, and chronic cough increased 9.6% (3.141, 1.776-5.555), 7.5% (2.468, 1.421-4.286), and 10.2% (1.787, 1.246-2.563) in Minqin comparison with Pingliang, respectively, and the differences were significant (p <.01).

Effects of theatrical smokes and fogs on respiratory health in the entertainment industry.

PubMed

Varughese, Sunil; Teschke, Kay; Brauer, Michael; Chow, Yat; van Netten, Chris; Kennedy, Susan M

2005-05-01

Theatrical fogs (glycol or mineral oil aerosols) are widely used in the entertainment industry to create special effects and make lighting visible. We studied 101 employees at 19 sites using fogs and measured personal fog exposures, across work shift lung function, and acute and chronic symptoms. Results were also compared to an external control population, studied previously. Chronic work-related wheezing and chest tightness were significantly associated with increased cumulative exposure to fogs (mineral oil and glycols) over the previous 2 years. Acute cough and dry throat were associated with acute exposure to glycol-based fogs; increased acute upper airway symptoms were associated with increased fog aerosol overall. Lung function was significantly lower among those working closest to the fog source. Mineral oil- and glycol-based fogs are associated with acute and chronic adverse effects on respiratory health among employees. Reducing exposure, through controls, substitution, and elimination where possible, is likely to reduce these effects. (c) 2005 Wiley-Liss, Inc.

Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. III. Acute and chronic effects of CAPs on heart rate, heart-rate fluctuation, and body temperature.

PubMed

Hwang, Jing-Shiang; Nadziejko, Christine; Chen, Lung Chi

2005-04-01

Normal mice (C57) and mice prone to develop atherosclerosis (ApoE-/-) were implanted with electrocardiograph (EKG), core body temperature, and motion transmitters were exposed daily for 6 h to Tuxedo, NY, concentrated ambient particles (CAPs) for 5 day/wk during the spring and summer of 2003. The series of 5-min EKG monitoring and body-temperature measurements were obtained for each animal in the CAPs and filtered air sham exposure groups. Our hypothesis was that chronic exposure could cause cumulative health effects. We used our recently developed nonparametric method to estimate the daily time periods that mean heart rates (HR), body temperature, and physical activity differed significantly between the CAPs and sham exposed group. CAPs exposure most affected heart rate between 1:30 a.m. and 4:30 a.m. With the response variables being the average heart rate, body temperature, and physical activity, we adopted a two-stage modeling approach to obtain the estimates of chronic and acute effects on the changes of these three response variables. In the first stage, a time-varying model estimated daily crude effects. In the second stage, the true means of the estimated crude effects were modeled with a polynominal function of time for chronic effects, a linear term of daily CAPs exposure concentrations for acute effects, and a random component for unknown noise. A Bayesian framework combined these two stages. There were significant decreasing patterns of HR, body temperature, and physical activity for the ApoE-/- mice over the 5 mo of CAPs exposure, with smaller and nonsignificant changes for the C57 mice. The chronic effect changes of the three response variables for ApoE-/- mice were maximal in the last few weeks. There was also a significant relationship between CAPs exposure concentration and short-term changes of heart rate in ApoE-/- mice during exposure. Response variables were also defined for examining fluctuations of 5-min heart rates within long (i.e., 3-6 h) and short time periods (i.e., approximately 15 min). The results for the ApoE-/- mice showed that heart-rate fluctuation within the longer periods increased to 1.35-fold by the end of exposure experiment, while the heart-rate fluctuation within 15 min decreased to 0.7-fold.

Effects of chronic perfluorooctanoic acid (PFOA) at low concentration on morphometrics, gene expression, and fecundity in zebrafish (Danio rerio).

PubMed

Jantzen, Carrie E; Toor, Fatima; Annunziato, Kate A; Cooper, Keith R

2017-04-01

Perfluorooctanoic acid (PFOA) is a persistent, toxic, anthropogenic chemical recalcitrant to biodegradation. Based on previous studies in lower and higher vertebrates, it was hypothesized that chronic, sub-lethal, embryonic exposure to PFOA in zebrafish (Danio rerio) would adversely impact fish development, survival, and fecundity. Zebrafish embryo/sac-fry were water exposed to 2.0 or 0nM PFOA from 3 to 120hpf, and juvenile to adult cohorts were fed spiked food (8 pM) until 6 months. After chronic exposure, PFOA exposed fish were significantly smaller in total weight and length. Gene expression analysis found a significant decrease of transporters slco2b1, slco4a1, slco3a1 and tgfb1a, and a significant increase of slco1d1 expression. PFOA exposed fish produced significantly fewer eggs with reduced viability and developmental stage delay in F 1 . Chronic, low-dose exposure of zebrafish to PFOA significantly altered normal development, survival and fecundity and would likely impact wild fish population fitness in watersheds chronically exposed to PFOA. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease

PubMed Central

2017-01-01

The overwhelming increase in the global incidence of obesity and its associated complications such as insulin resistance, atherosclerosis, pulmonary disease, and degenerative disorders including dementia constitutes a serious public health problem. The Inhibitor of DNA Binding/Differentiation-3 (ID3), a member of the ID family of transcriptional regulators, has been shown to play a role in adipogenesis and therefore ID3 may influence obesity and metabolic health in response to environmental factors. This review will highlight the current understanding of how ID3 may contribute to complex chronic diseases via metabolic perturbations. Based on the increasing number of reports that suggest chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs) within the human body are associated with metabolic disorders, we will also consider the impact of these chemicals on ID3. Improved understanding of the ID3 pathways by which exposure to EDCs can potentiate complex chronic diseases in populations with metabolic disorders (obesity, metabolic syndrome, and glucose intolerance) will likely provide useful knowledge in the prevention and control of complex chronic diseases associated with exposure to environmental pollutants. PMID:28785583

The influence of chronic and subacute exposure to lead on the levels of prolactin, leptin, osteopontin, and follistatin in humans.

PubMed

Dobrakowski, M; Kasperczyk, A; Czuba, Z P; Machoń-Grecka, A; Szlacheta, Z; Kasperczyk, S

2017-06-01

This study was designed to determine the levels of prolactin, leptin, osteopontin, and follistatin in workers chronically and subacutely exposed to lead compounds. The examined population consisted of three groups. The first group was composed of 56 male workers who were chronically exposed to lead for 13.38 ± 10.38 years. The second group served as a control group and consisted of 24 male administrative workers, while the third group included 32 male workers exposed to lead for 40 ± 3 days. The levels of leptin, osteopontin, and prolactin were significantly lower in the group of workers chronically exposed to lead than in the control group by 42%, 26%, and 41%, respectively. The levels of follistatin did not differ between those groups. The levels of all measured hormones did not change after a short-term exposure to lead compared to baseline. Chronic lead exposure is associated with significantly decreased level of prolactin, leptin, and osteopontin. Lead-induced changes in the levels of these hormones may disturb many functions of the human body, including the immune response, metabolism, reproduction, and bone turnover.

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes.

PubMed

Milton, Abul H; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A; Mitchell, Kane

2017-05-23

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low-moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations.

Cognitive Control Dysfunction in Workers Exposed to Manganese-Containing Welding Fume

PubMed Central

Al-Lozi, A; Nielsen, SS; Hershey, T; Birke, A; Checkoway, H; Criswell, SR; Racette, BA

2017-01-01

Background Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. Methods We examined the relationship between Mn exposure and cognitive control performance in 95 workers with varying intensity and duration (median 15.5 years) of exposure to welding fume. We performed linear regression to assess the association between exposure to Mn-containing welding fume and cognitive control tasks. Results Overall performance was inversely related to intensity of welding exposure (p=0.009) and was driven by the Two-Back and Letter Number Sequencing tests that assess working memory (both p=0.02). Conclusions Occupational exposure to Mn-containing welding fume may be associated with poorer working memory performance, and workers may benefit from practices that reduce exposure intensity. PMID:27862095

Study of the prevalence of chronic, non-specific lung disease and related health problems in the grain-handling industry. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rankin, J.; Bates, J.; Claremont, A.

1986-10-01

A total of 310 grain handlers was studied, with attention to prevalence and characteristics of clinical, psychological, immunological, radiological, serological blood and urine parameters to determine any apparent effects from grain-dust exposure. Grain handlers had a higher prevalence of respiratory symptoms and signs than did the city workers who comprised the comparison group. Evidence of accumulative respiratory effect due to recurring exposures to grain dust was found. Acute and chronic airway reactions were induced by exposure to grain dust. Wheezing and dyspnea on exposure were related to length of employment. Grain fever syndrome was prevalent. Cases of acute recurrent conjunctivitismore » and rhinitis were found along with skin pruritus, mainly on exposure to barley dust. Pesticide exposure caused temporary disabling symptoms. Lung function was adversely affected by grain-dust exposure. Exposure to grain mites and insects in contaminated cereal grain caused a reaction among grain workers.« less

Is benzene exposure from gasoline carcinogenic?

PubMed

Jamall, Ijaz S; Willhite, Calvin C

2008-02-01

This article questions the basis for benzene as the carcinogenic surrogate in deriving health risk-based 'clean-up levels' for gasoline-impacted soil and groundwater at leaking underground storage tank properties. The epidemiological evidence suggests that acute myelogenous leukemia (AML) associated with chronic occupational benzene exposure can be best described by sigmoid dose-response relationships. A review of the molecular toxicology and kinetics of benzene points to the existence of threshold mechanisms in the induction of leukemia. The toxicological and epidemiological literature on chronic exposure to unleaded gasoline indicates that the benzene exposures required to induce a measurable carcinogenic response are substantially greater than exposures likely to be encountered from exposure to gasoline at contaminated properties. Thus, assuming that theoretical cancer risks associated with exposure to benzene from gasoline reflect actual health risks associated with such environmental exposures to gasoline and using these theoretical cancer risks and cancer potency factors for benzene to dictate soil and groundwater clean up of gasoline are not scientifically defensible.

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes

PubMed Central

Milton, Abul H.; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A.; Mitchell, Kane

2017-01-01

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low–moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations. PMID:28545256

How Does Chronic Cigarette Smoke Exposure Affect Human Skin? A Global Proteomics Study in Primary Human Keratinocytes.

PubMed

Rajagopalan, Pavithra; Nanjappa, Vishalakshi; Raja, Remya; Jain, Ankit P; Mangalaparthi, Kiran K; Sathe, Gajanan J; Babu, Niraj; Patel, Krishna; Cavusoglu, Nükhet; Soeur, Jeremie; Pandey, Akhilesh; Roy, Nita; Breton, Lionel; Chatterjee, Aditi; Misra, Namita; Gowda, Harsha

2016-11-01

Cigarette smoking has been associated with multiple negative effects on human skin. Long-term physiological effects of cigarette smoke are through chronic and not acute exposure. Molecular alterations due to chronic exposure to cigarette smoke remain unclear. Primary human skin keratinocytes chronically exposed to cigarette smoke condensate (CSC) showed a decreased wound-healing capacity with an increased expression of NRF2 and MMP9. Using quantitative proteomics, we identified 4728 proteins, of which 105 proteins were overexpressed (≥2-fold) and 41 proteins were downregulated (≤2-fold) in primary skin keratinocytes chronically exposed to CSC. We observed an alteration in the expression of several proteins involved in maintenance of epithelial barrier integrity, including keratin 80 (5.3 fold, p value 2.5 × 10 -7 ), cystatin A (3.6-fold, p value 3.2 × 10 -3 ), and periplakin (2.4-fold, p value 1.2 × 10 -8 ). Increased expression of proteins associated with skin hydration, including caspase 14 (2.2-fold, p value 4.7 × 10 -2 ) and filaggrin (3.6-fold, p value 5.4 × 10 -7 ), was also observed. In addition, we report differential expression of several proteins, including adipogenesis regulatory factor (2.5-fold, p value 1.3 × 10 -3 ) and histone H1.0 (2.5-fold, p value 6.3 × 10 -3 ) that have not been reported earlier. Bioinformatics analyses demonstrated that proteins differentially expressed in response to CSC are largely related to oxidative stress, maintenance of skin integrity, and anti-inflammatory responses. Importantly, treatment with vitamin E, a widely used antioxidant, could partially rescue adverse effects of CSC exposure in primary skin keratinocytes. The utility of antioxidant-based new dermatological formulations in delaying or preventing skin aging and oxidative damages caused by chronic cigarette smoke exposure warrants further clinical investigations and multi-omics research.

Concomitant behavioral and PFC neuronal activity recorded following dose-response protocol of MPD in adult male rats.

PubMed

Venkataraman, Sidish S; Claussen, Catherine; Joseph, Michael; Dafny, Nachum

2017-04-01

The use of methylphenidate (MPD), a commonly prescribed drug to treat attention-deficit hyperactivity disorder (ADHD), has steadily increased over the past 25 years. This trend has been accompanied by more MPD abuse by ordinary individuals for its cognitive enhancing effects. Therefore, understanding the effects of MPD on the prefrontal cortex (PFC), a brain area involved in higher cortical processing such as executive function, language, planning, and attention regulation, is of particular importance. The goal of this study is to investigate the effects of acute and chronic dose-response characteristics following MPD exposure on both the PFC neuronal population and behavioral activity in freely behaving animals implanted previously with permanent electrodes within the PFC. Four groups of animals were used: saline (control), 0.6, 2.5, and 10.0mg/kg MPD. It was observed that the same dose of either 0.6, 2.5, or 10.0mg/kg repetitive (chronic) MPD exposure elicited behavioral sensitization in some animals and behavioral tolerance in others, and that the majority of PFC units recorded from animals expressing behavioral sensitization to chronic MPD exposure responded to MPD by increasing their neuronal firing rate, whereas the majority of PFC neurons recorded from animals expressing behavioral tolerance in response to chronic MPD responded by decreasing their neuronal firing rate. This data suggests that in animals that display behavioral sensitization, chronic MPD exposure causes an increase in the number of post-synaptic D1 dopamine receptors leading to an increase in behavioral and neuronal firing rate, while in animals that display behavioral tolerance, chronic MPD exposure causes an increase in the number of post-synaptic D2 dopamine receptors leading to a decrease in behavioral and neuronal firing rate. This dichotomy needs to be further investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

Determinants of Chronic Respiratory Symptoms among Pharmaceutical Factory Workers

PubMed Central

Enquselassie, Fikre; Tefera, Yifokire; Gizaw, Muluken; Wakuma, Samson; Woldemariam, Messay

2018-01-01

Background Chronic respiratory symptoms including chronic cough, chronic phlegm, wheezing, shortness of breath, and chest pain are manifestations of respiratory problems which are mainly evolved as a result of occupational exposures. This study aims to assess determinants of chronic respiratory symptoms among pharmaceutical factory workers. Methods A case control study was carried out among 453 pharmaceutical factory workers with 151 cases and 302 controls. Data was collected using pretested and structured questionnaire. The data was analyzed using descriptive statistics and bivariate and multivariate analysis. Result Previous history of chronic respiratory diseases (AOR = 3.36, 95% CI = 1.85–6.12), family history of chronic respiratory diseases (AOR = 2.55, 95% CI = 1.51–4.32), previous dusty working environment (AOR = 2.26, 95% CI = 1.07–4.78), ever smoking (AOR = 3.66, 95% CI = 1.05–12.72), and service years (AOR = 1.86, 95% CI = 1.16–2.99) showed statistically significant association with chronic respiratory symptoms. Conclusion Previous history of respiratory diseases, family history of chronic respiratory diseases, previous dusty working environment, smoking, and service years were determinants of chronic respiratory symptoms. Public health endeavors to prevent the burden of chronic respiratory symptoms among pharmaceutical factory workers should target the reduction of adverse workplace exposures and discouragement of smoking. PMID:29666655

Production and standing crop of litter and humus in a forest exposed to chronic gamma irradiation for twelve years

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armentano, T.V.; Woodwell, G.M.

Continuous exposure since 1961 of an oak-pine forest at Brookhaven National Laboratory to chronic gamma irradiation has shown: (1) progressive reduction in litter production from the first year through 1965; (2) greater litter production in 1973 compared to 1965 at exposure rates below 9 R/day primarily because of the prolific sprouting of the oaks, especially Quercus alba; (3) further reduction in litter production in intermediate zones (14-49 R/day) from 1965 to 1973 as a result of replacement of the forest by a Carex pensylvanica mat; (4) increased litter production in the high exposure zone (125 R/day) in 1973 as amore » result of colonization by adventive species; (5) reduction in the standing crop of litter by 1973 at the lowest exposure rate studied (3.5 R/day) although in 1965 there was no reduction at exposure rates up to 15 R/day; (6) decline in humus content at 4.6 R/day and above with the standing crop in the Carex zone exceeding that of the shrub and damaged forest zones of lower exposures. Both further losses and partial recovery in the production and storage of organic matter have occurred since 1965. These changes constitute a portion of the long-term response of the forest to chronic disturbance. The pattern of response is the result of ecosystem processes that are still not in equilibrium with the chronic disturbance and which were not predictable from short-term studies, even those spanning as much as 4 yr.« less

Effects of chronic exposure to clothianidin on the earthworm Lumbricus terrestris

PubMed Central

Goulson, Dave

2017-01-01

Although neonicotinoids are targeted at insects, their predominant use as a seed dressing and their long persistence in soils mean that non-target soil organisms such as earthworms are likely to be chronically exposed to them. Chronic exposure may pose risks that are not evaluated in most toxicity tests. We experimentally tested the effect of field-realistic concentrations of a commonly used neonicotinoid, clothianidin, on mortality, weight gain, and food consumption to assess the impacts of chronic exposure over four months on fitness of L. terrestris individuals. We undertook three separate experiments, each with different exposure routes: treated soil only (experiment A), treated food and soil combined (experiment B) and treated food only (experiment C). Mortality was negatively affected by exposure from treated soil only with greatest mortality observed in the groups exposed to the two highest concentrations (20 ppb and 100 ppb), but no clear effect on mortality was found in the other two experiments. When clothianidin was present in the food, an anti-feedant effect was present in months one and two which subsequently disappeared; if this occurs in the field, it could result in reduced rates of decomposition of treated crop foliage. We found no significant effects of any treatment on worm body mass. We cannot rule out stronger adverse effects if worms come into close proximity to treated seeds, or if other aspects of fitness were examined. Overall, our data suggest that field-realistic exposure to clothianidin has a significant but temporary effect on food consumption and can have weak but significant impacts on mortality of L. terrestris. PMID:28413730

The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon.

PubMed

Axelrad, J C; Howard, C V; McLean, W G

2003-03-14

Speculation about potential neurotoxicity due to chronic exposure to low doses of organophosphate (OP) pesticides is not yet supported by experimental evidence. The objective of this work was to use a cell culture model of chronic OP exposure to determine if such exposure can alter the sensitivity of nerve cells to subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells were grown in the presence of 25 microM diazinon for 8 weeks. The OP was then withdrawn and the cells were induced to differentiate in the presence of various other pesticides or herbicides, including OPs and OP-containing formulations. The resulting outgrowth of neurite-like structures was measured by light microscopy and quantitative image analysis and the IC(50) for each OP or formulation was calculated. The IC(50) values in diazinon-pre-exposed cells were compared with the equivalent values in cells not pre-exposed to diazinon. The IC(50) for inhibition of neurite outgrowth by acute application of diazinon, pyrethrum, glyphosate or a commercial formulation of glyphosate was decreased by between 20 and 90% after pre-treatment with diazinon. In contrast, the IC(50) for pirimiphos methyl was unaffected and those for phosmet or chlorpyrifos were increased by between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second glyphosate-containing formulation led to the formation of abnormal neurite-like structures in diazinon-pre-exposed cells. The data support the view that chronic exposure to an OP may reduce the threshold for toxicity of some, but by no means all, environmental agents.

Chronic exposure to arsenic, estrogen, and their combination causes increased growth and transformation in human prostate epithelial cells potentially by hypermethylation-mediated silencing of MLH1.

PubMed

Treas, Justin; Tyagi, Tulika; Singh, Kamaleshwar P

2013-11-01

Chronic exposure to arsenic and estrogen is associated with risk of prostate cancer, but their mechanism is not fully understood. Additionally, the carcinogenic effects of their co-exposure are not known. Therefore, the objective of this study was to evaluate the effects of chronic exposure to arsenic, estrogen, and their combination, on cell growth and transformation, and identify the mechanism behind these effects. RWPE-1 human prostate epithelial cells were chronically exposed to arsenic and estrogen alone and in combination. Cell growth was measured by cell count and cell cycle, whereas cell transformation was evaluated by colony formation assay. Gene expression was measured by quantitative real-time PCR and confirmed at protein level by Western blot analysis. MLH1 promoter methylation was determined by pyrosequencing method. Exposure to arsenic, estrogen, and their combinations increases cell growth and transformation in RWPE-1 cells. Increased expression of Cyclin D1 and Bcl2, whereas decreased expression of mismatch repair genes MSH4, MSH6, and MLH1 was also observed. Hypermethylation of MLH1 promoter further suggested the epigenetic inactivation of MLH1 expression in arsenic and estrogen treated cells. Arsenic and estrogen combination caused greater changes than their individual treatments. Findings of this study for the first time suggest that arsenic and estrogen exposures cause increased cell growth and survival potentially through epigenetic inactivation of MLH1 resulting in decreased MLH1-mediated apoptotic response, and consequently increased cellular transformation. © 2013 Wiley Periodicals, Inc.

Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

PubMed Central

Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

2013-01-01

Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

Chronic systemic pesticide exposure reproduces features of Parkinson's disease.

PubMed

Betarbet, R; Sherer, T B; MacKenzie, G; Garcia-Osuna, M; Panov, A V; Greenamyre, J T

2000-12-01

The cause of Parkinson's disease (PD) is unknown, but epidemiological studies suggest an association with pesticides and other environmental toxins, and biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity. Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and alpha-synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.

Occupational exposures and chronic obstructive pulmonary disease (COPD): comparison of a COPD-specific job exposure matrix and expert-evaluated occupational exposures

PubMed Central

Kurth, Laura; Doney, Brent; Weinmann, Sheila

2017-01-01

Objectives To compare the occupational exposure levels assigned by our National Institute for Occupational Safety and Health chronic obstructive pulmonary disease-specific job exposure matrix (NIOSH COPD JEM) and by expert evaluation of detailed occupational information for various jobs held by members of an integrated health plan in the Northwest USA. Methods We analysed data from a prior study examining COPD and occupational exposures. Jobs were assigned exposure levels using 2 methods: (1) the COPD JEM and (2) expert evaluation. Agreement (Cohen’s κ coefficients), sensitivity and specificity were calculated to compare exposure levels assigned by the 2 methods for 8 exposure categories. Results κ indicated slight to moderate agreement (0.19–0.51) between the 2 methods and was highest for organic dust and overall exposure. Sensitivity of the matrix ranged from 33.9% to 68.5% and was highest for sensitisers, diesel exhaust and overall exposure. Specificity ranged from 74.7% to 97.1% and was highest for fumes, organic dust and mineral dust. Conclusions This COPD JEM was compared with exposures assigned by experts and offers a generalisable approach to assigning occupational exposure. PMID:27777373

Disentangling the Exposure Experience: The Roles of Community Context and Report-Back of Environmental Exposure Data

ERIC Educational Resources Information Center

Adams, Crystal; Brown, Phil; Morello-Frosch, Rachel; Brody, Julia Green; Rudel, Ruthann; Zota, Ami; Dunagan, Sarah; Tovar, Jessica; Patton, Sharyle

2011-01-01

This article examines participants' responses to receiving their results in a study of household exposure to endocrine disrupting compounds and other pollutants. The authors study how the "exposure experience"--the embodied, personal experience and understanding of chronic exposure to environmental pollutants--is shaped by community…

Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence.

PubMed

Hashimoto, Joel G; Gavin, David P; Wiren, Kristine M; Crabbe, John C; Guizzetti, Marina

2017-05-01

Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitinationhylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study. Published by Elsevier Inc.

SILAC-based quantitative proteomic analysis reveals widespread molecular alterations in human skin keratinocytes upon chronic arsenic exposure.

PubMed

Mir, Sartaj Ahmad; Pinto, Sneha M; Paul, Somnath; Raja, Remya; Nanjappa, Vishalakshi; Syed, Nazia; Advani, Jayshree; Renuse, Santosh; Sahasrabuddhe, Nandini A; Prasad, T S Keshava; Giri, Ashok K; Gowda, Harsha; Chatterjee, Aditi

2017-03-01

Chronic exposure to arsenic is associated with dermatological and nondermatological disorders. Consumption of arsenic-contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs, and gastrointestinal tract. Although arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues including skin. Epidemiological studies suggest the association of skin cancer upon arsenic exposure, however, the mechanism of arsenic-induced carcinogenesis is not completely understood. We developed a cell line based model to understand the molecular mechanisms involved in arsenic-mediated toxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT, was chronically exposed to 100 nM sodium arsenite over a period of 6 months. We observed an increase in basal ROS levels in arsenic-exposed cells. SILAC-based quantitative proteomics approach resulted in identification of 2111 proteins of which 42 proteins were found to be overexpressed and 54 downregulated (twofold) upon chronic arsenic exposure. Our analysis revealed arsenic-induced overexpression of aldo-keto reductase family 1 member C2 (AKR1C2), aldo-keto reductase family 1 member C3 (AKR1C3), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) among others. We observed downregulation of several members of the plakin family including periplakin (PPL), envoplakin (EVPL), and involucrin (IVL) that are essential for terminal differentiation of keratinocytes. MRM and Western blot analysis confirmed differential expression of several candidate proteins. Our study provides insights into molecular alterations upon chronic arsenic exposure on skin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Micro RNA responses to chronic or acute exposures to low dose ionizing radiation

PubMed Central

Chaudhry, M. Ahmad; Omaruddin, Romaica A.; Kreger, Bridget; de Toledo, Sonia M.; Azzam, Edouard I.

2014-01-01

Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose c-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of 137Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate c-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation. PMID:22367372

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

PubMed Central

Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth

2016-01-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

PubMed

Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

2016-07-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by the Research Society on Alcoholism.

Ozone and Survival in Four Cohorts with Potentially Predisposing Diseases

PubMed Central

Schwartz, Joel

2011-01-01

Rationale: Time series studies have reported associations between ozone and daily deaths. Only one cohort study has reported the effect of long-term exposures on deaths, and little is known about effects of chronic ozone exposure on survival in susceptible populations. Objectives: We investigated whether ozone was associated with survival in four cohorts of persons with specific diseases in 105 United States cities, treating ozone as a time varying exposure. Methods: We used Medicare data (1985–2006), and constructed cohorts of persons hospitalized with chronic conditions that might predispose to ozone effects: chronic obstructive pulmonary disease, diabetes, congestive heart failure, and myocardial infarction. Yearly warm-season average ozone was merged to the individual follow-up in each city. We applied Cox proportional hazard model for each cohort within each city, adjusting for individual risk factors, temperature, and city-specific long-term trends. Measurements and Main Results: We found significant associations with a hazard ratio for mortality of 1.06 (95% confidence interval [CI], 1.03–1.08) per 5-ppb increase in summer average ozone for persons with congestive heart failure; of 1.09 (95% CI, 1.06–1.12) with myocardial infarction; of 1.07 (95% CI, 1.04–1.09) with chronic obstructive pulmonary disease; and of 1.07 (95% CI, 1.05–1.10) for diabetics. We also found that the effect varied by region, but that this was mostly explained by mean temperature, which is likely a surrogate of air conditioning use, and hence exposure. Conclusions: This is the first study that follows persons with specific chronic conditions, and shows that long-term ozone exposure is associated with increased risk of death in these groups. PMID:21700916

Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence

PubMed Central

Hashimoto, Joel G.; Gavin, David P.; Wiren, Kristine M.; Crabbe, John C.; Guizzetti, Marina

2017-01-01

Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitination, and in DNA methylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study. PMID:28433423

Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

USGS Publications Warehouse

Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

2016-01-01

The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

Non-malignant respiratory diseases and lung cancer among Chinese workers exposed to silica.

PubMed

Cocco, P; Rice, C H; Chen, J Q; McCawley, M; McLaughlin, J K; Dosemeci, M

2000-06-01

The objective of this study was to explore whether a medical history for non-malignant respiratory disease contributes to an increased lung cancer risk among workers exposed to silica. We analyzed data from a nested case-control study in 29 dusty workplaces in China. The study population consisted of 316 lung cancer cases and 1356 controls matched to cases by facility type and decade of birth who were alive at the time of diagnosis of the index case and who were identified in a follow-up study of about 68,000 workers. Age at first exposure and cigarette smoking were accounted for in the analysis. Smoking was the main risk factor for both lung cancer and chronic bronchitis. Lung cancer risk showed a modest association with silicosis and with cumulative silica exposure, which did not vary by history of previous pulmonary tuberculosis. Among subjects without a medical history for chronic bronchitis or asthma, lung cancer risk was associated with silicosis (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), and it was increased in each quartile of cumulative silica exposure. However, risk was not elevated in the highest quartile (OR, 1.3, 1.6, 1.8, 1.4). Among subjects with a medical history for chronic bronchitis or asthma, lung cancer risk was associated with neither silicosis (subjects with chronic bronchitis: OR, 0.6; subjects with asthma: OR, 0.4) nor with silica exposure. In this study population, we observed a modest association of both silicosis and cumulative exposure to silica with lung cancer among subjects who were not previously diagnosed with chronic bronchitis or asthma, but not among subjects who had a medical history for either disease. Risk of lung cancer associated with silicosis or cumulative exposure to silica did not vary by previous medical history of pulmonary tuberculosis.

Chronic Exposure to Low Doses of HgCl2 Avoids Calcium Handling Impairment in the Right Ventricle after Myocardial Infarction in Rats

PubMed Central

Faria, Thaís de Oliveira; Costa, Gustavo Pinto; Almenara, Camila Cruz Pereira; Angeli, Jhuli Keli; Vassallo, Dalton Valentim; Stefanon, Ivanita; Vassallo, Paula Frizera

2014-01-01

Right ventricle systolic dysfunction is a major risk factor for death and heart failure after myocardial infarction (MI). Heavy metal exposure has been associated with the development of several cardiovascular diseases, such as MI. The aim of this study was to investigate whether chronic exposure to low doses of mercury chloride (HgCl2) enhances the functional deterioration of right ventricle strips after MI. Male Wistar rats were divided into four groups: Control (vehicle); HgCl2 (exposure during 4 weeks- 1st dose 4.6 µg/kg, subsequent dose 0.07 µg/kg/day, i.m. to cover daily loss); MI surgery induced and HgCl2-MI groups. One week after MI, the morphological and hemodynamic measurements and isometric tension of right ventricle strips were investigated. The chronic HgCl2 exposure did not worsen the injury compared with MI alone in the morphological or hemodynamic parameters evaluated. At basal conditions, despite similar maximum isometric force at L-max, relaxation time was increased in the MI group but unaffected in the HgCl2-MI compared to the Control group. Impairment of the sarcoplasmic reticulum (SR) function and reduction in the sarcolemmal calcium influx were observed in MI group associated with SERCA2a reduction and increased PLB protein expression. Induction of MI in chronic HgCl2 exposed rats did not cause any alteration in the developed force at L-max, lusitropic function or −dF/dt except for a tendency of a reduction SR function. These findings could be partially explained by the normalization in the sarcolemmal calcium influx and the increase in NCX protein expression observed only in this group. These results suggest that chronic exposure to low doses of HgCl2 prevents the impaired SR function and the reduced sarcolemmal calcium influx observed in MI likely by acting on NCX, PLB and SERCA2a protein expression. PMID:24748367

Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome.

PubMed

Hoyt, Laura R; Randall, Matthew J; Ather, Jennifer L; DePuccio, Daniel P; Landry, Christopher C; Qian, Xi; Janssen-Heininger, Yvonne M; van der Vliet, Albert; Dixon, Anne E; Amiel, Eyal; Poynter, Matthew E

2017-08-01

Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774) amplifies IL-1β secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells), effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K + efflux or Zn 2+ homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD + . Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH) mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1β hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1β hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation. Copyright © 2017. Published by Elsevier B.V.

An ecological risk assessment of the acute and chronic effects of the herbicide clopyralid to rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Fairchild, J.F.; Allert, A.L.; Feltz, K.P.; Nelson, K.J.; Valle, J.A.

2009-01-01

Clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) is a pyridine herbicide frequently used to control invasive, noxious weeds in the northwestern United States. Clopyralid exhibits low acute toxicity to fish, including the rainbow trout (Oncorhynchus mykiss) and the threatened bull trout (Salvelinus confluentus). However, there are no published chronic toxicity data for clopyralid and fish that can be used in ecological risk assessments. We conducted 30-day chronic toxicity studies with juvenile rainbow trout exposed to the acid form of clopyralid. The 30-day maximum acceptable toxicant concentration (MATC) for growth, calculated as the geometric mean of the no observable effect concentration (68 mg/L) and the lowest observable effect concentration (136 mg/L), was 96 mg/L. No mortality was measured at the highest chronic concentration tested (273 mg/L). The acute:chronic ratio, calculated by dividing the previously published 96-h acutely lethal concentration (96-h ALC50; 700 mg/L) by the MATC was 7.3. Toxicity values were compared to a four-tiered exposure assessment profile assuming an application rate of 1.12 kg/ha. The Tier 1 exposure estimation, based on direct overspray of a 2-m deep pond, was 0.055 mg/L. The Tier 2 maximum exposure estimate, based on the Generic Exposure Estimate Concentration model (GEENEC), was 0.057 mg/L. The Tier 3 maximum exposure estimate, based on previously published results of the Groundwater Loading Effects of Agricultural Management Systems model (GLEAMS), was 0.073 mg/L. The Tier 4 exposure estimate, based on published edge-of-field monitoring data, was estimated at 0.008 mg/L. Comparison of toxicity data to estimated environmental concentrations of clopyralid indicates that the safety factor for rainbow trout exposed to clopyralid at labeled use rates exceeds 1000. Therefore, the herbicide presents little to no risk to rainbow trout or other salmonids such as the threatened bull trout. ?? 2009 US Government.

Estimated drinking water fluoride exposure and risk of hip fracture: a cohort study.

PubMed

Näsman, P; Ekstrand, J; Granath, F; Ekbom, A; Fored, C M

2013-11-01

The cariostatic benefit from water fluoridation is indisputable, but the knowledge of possible adverse effects on bone and fracture risk due to fluoride exposure is ambiguous. The association between long-term (chronic) drinking water fluoride exposure and hip fracture (ICD-7-9: '820' and ICD-10: 'S72.0-S72.2') was assessed in Sweden using nationwide registers. All individuals born in Sweden between January 1, 1900 and December 31, 1919, alive and living in their municipality of birth at the time of start of follow-up, were eligible for this study. Information on the study population (n = 473,277) was linked among the Swedish National In-Patient Register (IPR), the Swedish Cause of Death Register, and the Register of Population and Population Changes. Estimated individual drinking water fluoride exposure was stratified into 4 categories: very low, < 0.3 mg/L; low, 0.3 to 0.69 mg/L; medium, 0.7 to 1.49 mg/L; and high, ≥ 1.5 mg/L. Overall, we found no association between chronic fluoride exposure and the occurrence of hip fracture. The risk estimates did not change in analyses restricted to only low-trauma osteoporotic hip fractures. Chronic fluoride exposure from drinking water does not seem to have any important effects on the risk of hip fracture, in the investigated exposure range.

Hepatic and renal trace element concentrations in American alligators (Alligator mississippiensis) following chronic dietary exposure to coal fly ash contaminated prey.

PubMed

Tuberville, Tracey D; Scott, David E; Metts, Brian S; Finger, John W; Hamilton, Matthew T

2016-07-01

Little is known about the propensity of crocodilians to bioaccumulate trace elements as a result of chronic dietary exposure. We exposed 36 juvenile alligators (Alligator mississippiensis) to one of four dietary treatments that varied in the relative frequency of meals containing prey from coal combustion waste (CCW)-contaminated habitats vs. prey from uncontaminated sites, and evaluated tissue residues and growth rates after 12 mo and 25 mo of exposure. Hepatic and renal concentrations of arsenic (As), cadmium (Cd) and selenium (Se) varied significantly among dietary treatment groups in a dose-dependent manner and were higher in kidneys than in livers. Exposure period did not affect Se or As levels but Cd levels were significantly higher after 25 mo than 12 mo of exposure. Kidney As and Se levels were negatively correlated with body size but neither growth rates nor body condition varied significantly among dietary treatment groups. Our study is among the first to experimentally examine bioaccumulation of trace element contaminants in crocodilians as a result of chronic dietary exposure. A combination of field surveys and laboratory experiments will be required to understand the effects of different exposure scenarios on tissue residues, and ultimately link these concentrations with effects on individual health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

PubMed

Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

2018-03-01

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

PubMed Central

Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

2014-01-01

Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

Gene transcription patterns in response to low level petroleum contaminants in Mytilus trossulus from field sites and harbors in southcentral Alaska

NASA Astrophysics Data System (ADS)

Bowen, Lizabeth; Miles, A. Keith; Ballachey, Brenda; Waters, Shannon; Bodkin, James; Lindeberg, Mandy; Esler, Daniel

2018-01-01

The 1989 Exxon Valdez oil spill damaged a wide range of natural resources, including intertidal communities, and post-spill studies demonstrated acute and chronic exposure and injury to an array of species. Standard toxicological methods to evaluate petroleum contaminants have assessed tissue burdens, with fewer assays providing indicators of health or physiology, particularly when contaminant levels are low and chronic. Marine mussels are a ubiquitous and crucial component of the nearshore environment, and new genomic technologies exist to quantify molecular responses of individual mussels to stimuli, including exposure to polycyclic aromatic hydrocarbons (PAHs). We used gene-based assays of exposure and physiological function to assess chronic oil contamination using the Pacific blue mussel, Mytilus trossulus. We developed a diagnostic gene transcription panel to investigate exposure to PAHs and other contaminants and its effects on mussel physiology and health. During 2012-2015, we analyzed mussels from five field sites in western Prince William Sound, Alaska, with varying oil histories from the 1989 Exxon Valdez oil spill, and from three boat harbors in the area. Gene transcription patterns of mussels from harbors were consistent with elevated exposure to PAHs or other contaminants, whereas transcription patterns of mussels sampled from shorelines in areas affected by the oil spill indicated no PAH exposure.

Chronic stress and sex differences on the recall of fear conditioning and extinction.

PubMed

Baran, Sarah E; Armstrong, Charles E; Niren, Danielle C; Hanna, Jeffery J; Conrad, Cheryl D

2009-03-01

Chronic stress effects and sex differences were examined on conditioned fear extinction. Male and female Sprague-Dawley rats were chronically stressed by restraint (6 h/d/21 d), conditioned to tone and footshock, followed by extinction after 1 h and 24 h delays. Chronic stress impaired the recall of fear extinction in males, as evidenced by high freezing to tone after the 24 h delay despite exposure to the previous 1 h delay extinction trials, and this effect was not due to ceiling effects from overtraining during conditioning. In contrast, chronic stress attenuated the recall of fear conditioning acquisition in females, regardless of exposure to the 1 h extinction exposure. Since freezing to tone was reinstated following unsignalled footshocks, the deficit in the stressed rats reflected impaired recall rather than impaired consolidation. Sex differences in fear conditioning and extinction were observed in nonstressed controls as well, with control females resisting extinction to tone. Analysis of contextual freezing showed that all groups (control, stress, male, female) increased freezing immediately after the first tone extinction trial, demonstrating contextual discrimination. These findings show that chronic stress and sex interact to influence fear conditioning, with chronic stress impairing the recall of delayed fear extinction in males to implicate the medial prefrontal cortex, disrupting the recall of the fear conditioning acquisition in females to implicate the amygdala, and nonstressed controls exhibiting sex differences in fear conditioning and extinction, which may involve the amygdala and/or corticosterone levels.

Physiological response of juvenile rainbow trout to chronic low level exposures of waterborne silver.

PubMed

Galvez, F; Hogstrand, C; Wood, C M

1998-02-01

The physiological effects of chronic exposure to AgNO3 in moderately hard freshwater were investigated in juvenile rainbow trout (Oncorhynchus mykiss Walbaum). Two separate 28-day exposures were performed at silver concentrations of 0.5 and 2.0 micrograms/L in flowing Hamilton dechlorinated tap water. Exposure to 0.5 microgram/L Ag resulted in a slight increase (approximately 14.9%) in food consumption, whereas growth rates remained unaltered. Both plasma Na+ and Cl- levels were significantly decreased by 11.8% and 9.3%, respectively at day 16 of the exposure. Hepatic Ag concentrations were elevated approximately 4-fold in 0.5 microgram/L Ag-exposed fish. However, no significant increases in liver metallothionein (MT) concentrations were noted. No mortalities were observed during this 28-day exposure. In comparison, chronic exposure to 2.0 micrograms/L Ag resulted in a 28.8% decrease in food consumption and a 43.0% reduction in growth rate. Plasma [Na+] was decreased by 18.3%, whereas plasma [Cl-] was reduced by 12.2% at day 7. At both concentrations of silver, plasma ion concentrations appeared to recover thereafter. Silver accumulated steadily in the liver up until day 15 when concentrations were 39.7 micrograms/g wet weight (285-fold increase) above control levels. In addition, MT levels were increased by 81.2% at day 7. Silver exposure at 2.0 micrograms/L resulted in approximately 15.0% mortality over the 28-day period.

Long-Term Fine Particulate Matter Exposure and Major Depressive Disorder in a Community-Based Urban Cohort

PubMed Central

Kim, Kyoung-Nam; Lim, Youn-Hee; Bae, Hyun Joo; Kim, Myounghee; Jung, Kweon; Hong, Yun-Chul

2016-01-01

Background: Previous studies have associated short-term air pollution exposure with depression. Although an animal study showed an association between long-term exposure to particulate matter ≤ 2.5 μm (PM2.5) and depression, epidemiological studies assessing the long-term association are scarce. Objective: We aimed to determine the association between long-term PM2.5 exposure and major depressive disorder (MDD). Methods: A total of 27,270 participants 15–79 years of age who maintained an address within the same districts in Seoul, Republic of Korea, throughout the entire study period (between 2002 and 2010) and without a previous MDD diagnosis were analyzed. We used three district-specific exposure indices as measures of long-term PM2.5 exposure. Cox proportional hazards models adjusted for potential confounding factors and measured at district and individual levels were constructed. We further conducted stratified analyses according to underlying chronic diseases such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary disease. Results: The risk of MDD during the follow-up period (2008–2010) increased with an increase of 10 μg/m3 in PM2.5 in 2007 [hazard ratio (HR) = 1.44; 95% CI: 1.17, 1.78], PM2.5 between 2007 and 2010 (HR = 1.59; 95% CI: 1.02, 2.49), and 12-month moving average of PM2.5 until an event or censor (HR = 1.47; 95% CI: 1.14, 1.90). The association between long-term PM2.5 exposure and MDD was greater in participants with underlying chronic diseases than in participants without these diseases. Conclusion: Long-term PM2.5 exposure increased the risk of MDD among the general population. Individuals with underlying chronic diseases are more vulnerable to long-term PM2.5 exposure. Citation: Kim KN, Lim YH, Bae HJ, Kim M, Jung K, Hong YC. 2016. Long-term fine particulate matter exposure and major depressive disorder in a community-based urban cohort. Environ Health Perspect 124:1547–1553; http://dx.doi.org/10.1289/EHP192 PMID:27129131

Hazardous Post Anesthesia Care Unit (PACU): Reality or Myth? A Case Study

DTIC Science & Technology

2000-01-03

speculation of trace anesthetic gases being associated with miscarriages and birth defects. Concerns led to a conference of several government agencies...nitrous oxide may cause depression of vitamin B12 and chronic low level exposure inhibits methionine synthase which impairs synthesis of...depression of vitamin B12 and chronic low level exposure inhibits methionine synthase which impairs synthesis of deoxyribonucleic acid and bone marrow

Feasibility of Epidemiologic Research on Nonauditory Health Effects of Residential Aircraft Noise Exposure. Volume 2. Background, General Process Model and Potential Studies

DTIC Science & Technology

1989-01-27

Epidemiologic Study in 120 Oklahoma City 5.4 Chronic Exposure to Sonic Booms 122 5.4.1 White Sands Missile Range 122 5.4.2 Areas Overflown by SR-71 123...5.5 Chronic Exposure to Subsonic Civil Aircraft Noise 123 5.5.1 Design of an Ecologic Study in Airport Environs 124 Iv 5.5.2 Preliminary Evaluation of...dosage-effect relationships for different groups of individuals, one must be able to argue convincingly that a noise measure reflects some aspect of

Chronic respiratory effects of indoor formaldehyde exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krzyzanowski, M.; Quackenboss, J.J.; Lebowitz, M.D.

The relation of chronic respiratory symptoms and pulmonary function to formaldehyde (HCHO) in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. HCHO measurements were made with passive samplers two one-week periods. Data on chronic cough and phlegm, wheeze, attacks of breathlessness, and doctor diagnoses of chronic bronchitis and asthma were collected with self-completed questionnaires. Peak expiratory flow rates (PEFR) were obtained during the evenings and mornings for up to 14 consecutive days for each individual. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with HCHOmore » levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR linearly decreased with HCHO exposure, with estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children.« less

Protracted effects of chronic stress on serotonin-dependent thermoregulation.

PubMed

Natarajan, Reka; Northrop, Nicole A; Yamamoto, Bryan K

2015-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. The body temperature is controlled in part, by the medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress (CUS) paradigm produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four days after the last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10 °C were recorded. The CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that the CUS induced changes to the 5HTergic system alter mPOA function in thermoregulation. These findings help us to explain the mechanisms underlying chronic stress-induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed.

Protracted effects of chronic stress on serotonin dependent thermoregulation

PubMed Central

Natarajan, Reka; Northrop, Nicole A.; Yamamoto, Bryan K.

2016-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. Body temperature is controlled in part, by the medial preoptic area of the hypothalamus (mPOA). To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress paradigm (CUS) produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 days of CUS. Four days after last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10°C were recorded. CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that CUS induced changes to the 5HTergic system alters mPOA function in thermoregulation. These findings help explain mechanisms underlying chronic stress induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed. PMID:26414686

Association between Low to Moderate Arsenic Exposure and Incident Cardiovascular Disease. A Prospective Cohort Study

PubMed Central

Moon, Katherine A.; Guallar, Eliseo; Umans, Jason G.; Devereux, Richard B.; Best, Lyle G.; Francesconi, Kevin A.; Goessler, Walter; Pollak, Jonathan; Silbergeld, Ellen K.; Howard, Barbara V.; Navas-Acien, Ana

2014-01-01

Background Inorganic arsenic exposure in water and food is a global public health problem. Chronic exposure to high levels of arsenicis consistently associated with increased risk of cardiovascular disease, whereas prospective data on low to moderate chronic arsenic exposure (<100μg/L in drinking water) are lacking. Objective To evaluate the association between chronic low to moderate arsenic exposure and incident cardiovascular disease. Design Prospective cohort study. Setting The Strong Heart Study baseline visit in 1989-1991, with follow-up through 2008. Patients 3,575 American Indian men and women aged 45-74 years living in Arizona, Oklahoma, and North and South Dakota. Measurements The sum of inorganic and methylated arsenic species in urine at baseline was used as a biomarker of chronic arsenic exposure. Participants were followed for incident fatal and non-fatal cardiovascular disease, including coronary heart disease and stroke. Results 1,184 participants developed fatal and non-fatal cardiovascular disease and 439 participants developed fatal cardiovascular disease. Comparing the highest to lowest quartile arsenic concentrations (>15.7 vs. <5.8 μg/g creatinine), the hazard ratios (95% confidence interval) for cardiovascular disease, coronary heart disease, and stroke mortality after adjustment for socio-demographic factors, smoking, body mass index, and lipids were 1.65 (1.20, 2.27; p-trend<0.001), 1.71 (1.19, 2.44; p-trend<0.001) and 3.03 (1.08, 8.50; p-trend=0.061), respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, and stroke were 1.32 (1.09, 1.59; p-trend=0.002), 1.30 (1.04, 1.62; p-trend=0.006), and 1.47 (0.97, 2.21; p-trend=0.032), respectively. These associations varied by study region and were attenuated following further adjustment for diabetes, hypertension, and measures of kidney disease. Limitations Direct measurement of individual arsenic in drinking water was unavailable. Residual confounding and differences in potential confounders across study regions may exist. Conclusions Low to moderate chronic arsenic exposure, as measured in urine, was prospectively associated with cardiovascular disease incidence and mortality. PMID:24061511

Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model.

PubMed

Laube, Beth L; Afshar-Mohajer, Nima; Koehler, Kirsten; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

2017-04-01

To determine the effect of an acute (1 week) and chronic (3 weeks) exposure to E-cigarette (E-cig) emissions on mucociliary clearance (MCC) in murine lungs. C57BL/6 male mice (age 10.5 ± 2.4 weeks) were exposed for 20 min/day to E-cigarette aerosol generated by a Joyetech 510-T ® E-cig containing either 0% nicotine (N)/propylene glycol (PG) for 1 week (n = 6), or 3 weeks (n = 9), or 2.4% N/PG for one week (n = 6), or 3 weeks (n = 9), followed by measurement of MCC. Control mice (n = 15) were not exposed to PG alone, or N/PG. MCC was assessed by gamma camera following aspiration of 99m technetium aerosol and was expressed as the amount of radioactivity removed from both lungs over 6 hours (MCC6hrs). Venous blood was assayed for cotinine levels in control mice and in mice exposed for 3-weeks to PG alone and N/PG. MCC6hrs in control mice and in mice acutely exposed to PG alone and N/PG was similar, averaging (±1 standard deviation) 8.6 ± 5.2%, 7.5 ± 2.8% and 11.2 ± 5.9%, respectively. In contrast, chronic exposure to PG alone stimulated MCC6hrs (17.2 ± 8.0)% and this stimulation was significantly blunted following chronic exposure to N/PG (8.7 ± 4.6)% (p < .05). Serum cotinine levels were <0.5 ng/ml in control mice and in mice exposed to PG alone, whereas, N/PG exposed mice averaged 14.6 ± 12.0 ng/ml. In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine.

Chronic stress effects and their reversibility on the Fallopian tubes and uterus in rats.

PubMed

Divyashree, S; Yajurvedi, H N

2018-01-01

The durational effects of chronic stress on the Fallopian tubes and uterus were studied by exposing rats to stressors in the form of restraint (1h) and forced swimming (15min) daily for 4, 8 or 12 weeks. One group of stressed rats from each time period was then maintained without exposure to stressors for a further 4 weeks to assess their ability to recover from stress. All time periods of stress exposure resulted in decreased weight of the body and Fallopian tubes; however, the relative weight of the uterus and serum concentrations of oestradiol and insulin increased significantly. The antioxidant potential was decreased with increased malondialdehyde concentrations in the Fallopian tubes following all durations of exposure and after 4 and 8 weeks of stress exposure in the uterus. Interestingly, rats stressed for 12 weeks showed an increase in serum testosterone concentration and antioxidant enzyme activities with a decrease in malondialdehyde concentration in the uterus. The antioxidant enzyme activities and malondialdehyde concentration in the Fallopian tubes of all recovery group rats were similar to stressed rats. However, in the uterus these parameters were similar to controls in recovery group rats after 4 weeks or 8 weeks of exposure, but after 12 weeks of stress exposure these parameters did not return to control levels following the recovery period. These results reveal, for the first time, that chronic stress elicits an irreversible decrease in antioxidant defence in the Fallopian tubes irrespective of exposure duration, whereas the uterus develops reversible oxidative stress under short-term exposure but increased antioxidant potential with endometrial proliferation following long-term exposure.

Respiratory symptoms and conditions related to occupational exposures in machine shops.

PubMed

Jaakkola, Maritta S; Suuronen, Katri; Luukkonen, Ritva; Järvelä, Merja; Tuomi, Timo; Alanko, Kristiina; Mäkelä, Erja A; Jolanki, Riitta

2009-01-01

Since there are few data on the effects of metalworking in populations representing a variety of metal companies or on dose-response relationships concerning metalworking, this study investigated the relationship between occupational exposures in machine shops and the occurrence of upper and lower respiratory symptoms, asthma, and chronic bronchitis. A cross-sectional study of 726 male machine workers and 84 male office workers from 64 companies was conducted in southern Finland. All of the participants filled out a questionnaire, and aerosol measurements were performed in 57 companies. Exposure to metalworking fluids (MWF) showed a greater risk [odds ratio (OR)>or=2) for upper-airway symptoms, cough, breathlessness, and current asthma than exposures in office work did. Exposure to aerosol levels above the median (>or=0.17 mg/m3 in the general workshop air) was related to an increased risk (OR>or=2) of nasal and throat symptoms, cough, wheezing, breathlessness, chronic bronchitis, and current asthma. Machine workers with a job history of >or=15 years experienced increased throat symptoms, cough, and chronic bronchitis. This large study representing machine shops in southern Finland showed that machine workers experience increased nasal and throat symptoms, cough, wheezing, breathlessness, and asthma even in environments with exposure levels below the current occupational exposure limit for oil mists. The study suggests that improving machine shop environments could benefit the health of this workforce. It also suggests that it is time to consider reducing the current Finnish occupational exposure limit for oil mist or introducing the use of other health-relevant indicators of exposure.

Methamphetamine exposure and chronic illness in police officers

PubMed Central

Ross, Gerald H; Sternquist, Marie C

2012-01-01

Background: The medical literature reports health hazards for law enforcement personnel from repeated exposure to methamphetamine and related chemical compounds. Most effects appear transitory, but some Utah police officers with employment-related methamphetamine exposures developed chronic symptoms, some leading to disability. This report is of an uncontrolled retrospective medical chart evaluation of symptomatic officers treated with a sauna detoxification protocol designed to reduce the chronic symptoms and improve the quality of life. Methods: Sixty-nine officers consecutively entering the Utah Meth Cops Project were assessed before and after a treatment program involving gradual exercise, comprehensive nutritional support and physical sauna therapy. Evaluations included pre- and post-treatment scores of the Research and Development Corporation (RAND) 36-item Short Form Health Survey (SF-36) in comparison with RAND population norms, pre- and post-treatment symptom score intensities, neurotoxicity scores, Mini-Mental Status Examination, presenting symptom frequencies and a structured evaluation of treatment program safety. Results: Statistically significant health improvements were seen in the SF-36 evaluations, symptom scores and neurotoxicity scores. The detoxification protocol was well tolerated, with a 92.8% completion rate. Conclusions: This investigation strongly suggests that utilizing sauna and nutritional therapy may alleviate chronic symptoms appearing after chemical exposures associated with methamphetamine-related law enforcement activities. This report also has relevance to addressing the apparent ill effects of other complex chemical exposures. In view of the positive clinical outcomes in this group, broader investigation of this sauna-based treatment regimen appears warranted. PMID:22089658

Chronic repeated exposure to weather-related stimuli elicits few symptoms of chronic stress in captive molting and non-molting European starlings (Sturnus vulgaris).

PubMed

de Bruijn, Robert; Reed, J Michael; Romero, L Michael

2017-10-01

Repeated exposure to acute stressors causes dramatic changes in an animal's stress physiology and the cumulative effects are often called chronic stress. Recently we showed that short-term exposure to weather-related stimuli, such as temperature change, artificial precipitation, and food restriction, cause acute responses in captive European starlings (Sturnus vulgaris). Here, we examined the effect of repeated exposure to weather-related stressors on heart rate and corticosterone (CORT) of captive non-molting and molting European starlings. Four times every day for 3 weeks, birds were exposed to either 30 min of a subtle (3°C) decrease in temperature, a short bout of simulated rain, or 2 hr of food removal. The order and time of presentation were randomly assigned on each day. We found no differences in heart rate or heart rate variability. Furthermore, there were no changes in baseline CORT levels, CORT negative feedback efficacy, or maximal adrenal capacity. Mass increased across the experimental period only in molting birds. CORT responses to restraint were decreased in both groups following treatment, suggesting the birds had downregulated their responses to acute stress. Molting birds showed evidence of suppression of the HPA axis compared with non-molting birds, which is consistent with previous research. Overall, our data show that repeated exposure to weather-related stressors does not elicit most of the symptoms normally associated with chronic stress. © 2018 Wiley Periodicals, Inc.

Benzene and its methyl-derivatives: derivation of maximum exposure levels in automobiles.

PubMed

Schupp, Thomas; Bolt, Hermann M; Jaeckh, Rudolf; Hengstler, Jan G

2006-01-05

Automobile drivers are exposed to several organic hydrocarbons. Concentrations measured in passenger compartments have been reported to range between 13 and 560 microg/m(3) for benzene, 33-258 microg/m(3) for toluene, 20-250 microg/m(3) for xylene (mixed isomers) and 3-23 microg/m(3) for trimethylbenzene (mixed isomers). These aromatic hydrocarbons are emitted from gasoline and from materials inside a car. In the present study we evaluated, whether these exposures pose a potential risk to the health of drivers. Therefore, we derived maximum exposure levels inside cars for chronic (ELIA(chronic)) and short-term (STELIA) exposure. The lowest ELIA's(chronic) for benzene, toluene, xylene and trimethylbenzene were 0.083, 1.2, 8.8 and 0.31 mg/m(3), respectively. The respective STELIA's were 16, 30, 29 and 25 mg/m(3). Obviously concentrations of toluene, xylene and trimethylbenzene inside cars do not exceed their individual STELIA's. In contrast, benzene seems to be problematic, since concentrations inside cars amount up to 0.56 mg/m(3), which exceeds the ELIA(chronic) derived for benzene. This should not be underestimated, since benzene is a genotoxic carcinogen that probably acts by non-threshold mechanisms. In conclusion, concentrations of toluene, xylene and trimethylbenzene usually observed inside cars are unlikely to pose a risk to the health of drivers. A systematic toxicological evaluation of the risk associated with benzene exposure in cars seems to be necessary.

Association between change of health care providers and pregnancy exposure to FDA category C, D and X drugs.

PubMed

Yang, Jianzhou; Xie, Rihua; Krewski, Daniel; Wang, Yongjin; Walker, Mark; Cao, Wenjun; Wen, Shi Wu

2014-01-01

Changing health care providers frequently breaks the continuity of care, which is associated with many health care problems. The purpose of this study was to examine the association between a change of health care providers and pregnancy exposure to FDA category C, D and X drugs. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 were chosen for this study. The association between the number of changes in health care providers and with pregnancy exposure to category C, D, and X drugs for those women with and without chronic diseases were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 568 women were included in this study. Rates of FDA C, D, and X drug uses were 14.35%, 17.07%, 21.72%, and 31.14%, in women with no change of provider, 1-2 changes, 3-5 changes, and more than 5 changes of health care providers. An association between the number of changes of health care providers and pregnancy exposure to FDA C, D, and X drugs existed in women without chronic diseases but not in women with chronic disease. Change of health care providers is associated with pregnancy exposure to FDA category C, D and X drugs in women without chronic diseases.

Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells

NASA Technical Reports Server (NTRS)

Boyd, Nolan L.; Park, Heonyong; Yi, Hong; Boo, Yong Chool; Sorescu, George P.; Sykes, Michelle; Jo, Hanjoong

2003-01-01

Caveolae are plasmalemmal domains enriched with cholesterol, caveolins, and signaling molecules. Endothelial cells in vivo are continuously exposed to shear conditions, and their caveolae density and location may be different from that of static cultured cells. Here, we show that chronic shear exposure regulates formation and localization of caveolae and caveolin-1 in bovine aortic endothelial cells (BAEC). Chronic exposure (1 or 3 days) of BAEC to laminar shear increased the total number of caveolae by 45-48% above static control. This increase was due to a rise in the luminal caveolae density without changing abluminal caveolae numbers or increasing caveolin-1 mRNA and protein levels. Whereas some caveolin-1 was found in the plasma membrane in static-cultured cells, it was predominantly localized in the Golgi. In contrast, chronic shear-exposed cells showed intense caveolin-1 staining in the luminal plasma membrane with minimum Golgi association. The preferential luminal localization of caveolae may play an important role in endothelial mechanosensing. Indeed, we found that chronic shear exposure (preconditioning) altered activation patterns of two well-known shear-sensitive signaling molecules (ERK and Akt) in response to a step increase in shear stress. ERK activation was blunted in shear preconditioned cells, whereas the Akt response was accelerated. These results suggest that chronic shear stimulates caveolae formation by translocating caveolin-1 from the Golgi to the luminal plasma membrane and alters cell signaling responses.

Glucoregulatory responses of adult and aged rats after exposure to chronic stress.

PubMed

Odio, M R; Brodish, A

1990-01-01

Stress has been implicated as an environmental factor that may accelerate the process of biological aging. However, this proposal has remained largely anecdotal due to relatively few studies that directly tested this hypothesis. In the present experiments groups of 6-month-old and 20-month-old male F-344 rats were chronically stressed for a six-month period. After the last stress session, when the animals were 12 months of age (adult) and 26 months of age (old), control and chronically stressed rats were tested for their ability to: (a) elicit glucose and insulin responses to an acute, novel stressor; (b) remove a circulatory glucose load elicited either by acute stress exposure or by injection of d-glucose; and (c) raise insulin levels after a glucose challenge. In control rats, we observed a deficit in each of these parameters in old compared to adult rats. Exposure to chronic stress did not exacerbate deterioration of these response mechanisms in either adult or old rats. In fact, the data showed a modest improvement in glucose tolerance in chronically stressed compared to age-matched control rats. We conclude that chronic stress did not exacerbate age-dependent decline of glucoregulatory capacity. From these results and from our earlier work, we speculate that the decline during aging of the functional integrity of systems involved in the response to stress may be sustained by periodic challenges from the organism's external environment.

The Australian Vietnam Veterans Health Study: II. self-reported health of veterans compared with the Australian population.

PubMed

O'Toole, B I; Marshall, R P; Grayson, D A; Schureck, R J; Dobson, M; Ffrench, M; Pulvertaft, B; Meldrum, L; Bolton, J; Vennard, J

1996-04-01

Self-reported physical health status of Australian Vietnam veterans was determined 20-25 years after the war and its relation to combat was investigated. An epidemiological cohort study of a simple random sample of Army veterans posted to Vietnam between 1964 and 1972 was conducted with personal interviews using the Australian Bureau of Statistics Health Interview Survey questionnaire to compare veterans with the Australian population and a 21-item combat exposure index used to measure the relationship of combat to physical health. Veterans reported greater health service usage and more recent health actions than population expectations. They also reported excess health problems in almost all recent illness disease categories except endocrine conditions and cardiovascular conditions; only 6 of 37 chronic disease groups were not elevated compared to the population. Adjustment for non-response changed estimates only slightly. Combat exposure was significantly related to reports of recent and chronic mental disorders, recent hernia and chronic ulcer, recent eczema and chronic rash, deafness, chronic infective and parasitic disease, chronic back disorders and symptoms, signs and ill-defined conditions. Combat exposure may have significantly increased reports of only some health problems. A general position to complain as a result of psychological conditions due to combat is not consistent with the lack of relationship between combat and reports of physical conditions.

The Impact of Chronic Pesticide Exposure on Neuropsychological Functioning

ERIC Educational Resources Information Center

Schultz, Caitlin G.; Ferraro, F. Richard

2013-01-01

This study compared neuropsychological test performance of individuals (n = 18) with an occupational history of pesticide exposure to individuals (n = 35) with no such exposure history. Results showed that a history of pesticide-related occupation exposure led to deficits in only Digit Symbol performance. Additionally, the correlation between…

BEHAVIORAL ASSESSMENTS OF LONG EVANS RATS FOLLOWING A 13-WEEK SUBCHRONIC TOLUENE EXPOSURE.

EPA Science Inventory

The current study sought to develop an animal model of the neurotoxicity of long-term exposure to volatile organic compounds (VOCs) which may be used to predict the effects of chronic exposure to VOCs on public health. The effects of Subchronic inhalation exposure to toluene (0,...

Controlled exposure of volunteers with chronic obstructive pulmonary disease to sulfur dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linn, W.S.; Fischer, D.A.; Shamoo, D.A.

1985-08-01

Twenty-four volunteers with chronic obstructive pulmonary disease (COPD) were exposed to sulfur dioxide (SO/sub 2/) at 0, 0.4, and 0.8 ppm in an environmental control chamber. Exposures lasted 1 hr and included two 15-min exercise periods (mean exercise ventilation rate 18 liter/min). Pulmonary mechanical function was evaluated before exposures, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry before exposure and during the second exercise period. Symptoms were recorded throughout exposure periods and for 1 week afterward. No statistically significant changes in physiology or symptoms could be attributed to SO/sub 2/ exposure. Oldermore » adults with COPD seem less reactive to a given concentration of SO/sub 2/ than heavily exercising young adult asthmatics. This may be due to lower ventilation rates (i.e., lower SO/sub 2/ dose rates) and/or to lower airway reactivity in the COPD group.« less

N-hexane exposure: a cause of small fiber neuropathy.

PubMed

Guimarães-Costa, Raquel; Schoindre, Yoland; Metlaine, Arnaud; Lefaucheur, Jean-Pascal; Camdessanché, Jean-Philippe; Maisonobe, Thierry; Léger, Jean-Marc

2018-06-01

A 59-year-old woman presented with progressive paresthesias of all of her limbs for 4 years, associated with neuropathic pain, tingling in the tongue and allodynia, consistent with small fiber neuropathy (SFN). Several systemic symptoms and signs were found on clinical examination and laboratory work-up. Neurological investigations including neurophysiologic test and skin biopsy supported the diagnosis of SFN. Chronic exposure to N-hexane was then disclosed and suspected to be the cause of the disease. Following the discontinuation of chronic N-hexane exposure, the patient had a progressive improvement of all signs and symptoms, reinforcing the correlation between exposure to N-hexane, and development of SFN. Exposure to N-hexane may be considered as a novel reversible cause of SFN, which underlines the need to look for toxic etiologies in the diagnosis of SFN. © 2018 Peripheral Nerve Society.

Lifetime Occupational Exposure to Dusts, Gases and Fumes Is Associated with Bronchitis Symptoms and Higher Diffusion Capacity in COPD Patients

PubMed Central

Rodríguez, Esther; Ferrer, Jaume; Zock, Jan-Paul; Serra, Ignasi; Antó, Josep M.; de Batlle, Jordi; Kromhout, Hans; Vermeulen, Roel; Donaire-González, David; Benet, Marta; Balcells, Eva; Monsó, Eduard; Gayete, Angel; Garcia-Aymerich, Judith

2014-01-01

Background Occupational exposure to dusts, gases and fumes has been associated with reduced FEV1 and sputum production in COPD patients. The effect of occupational exposure on other characteristics of COPD, especially those reflecting emphysema, has not been studied in these patients. Methods We studied 338 patients hospitalized for a first exacerbation of COPD in 9 Spanish hospitals, obtaining full occupational history in a face-to-face interview; job codes were linked to a job exposure matrix for semi-quantitative estimation of exposure to mineral/biological dust, and gases/fumes for each job held. Patients underwent spirometry, diffusing capacity testing and analysis of gases in stable conditions. Quality of life, dyspnea and chronic bronchitis symptoms were determined with a questionnaire interview. A high- resolution CT scan was available in 133 patients. Results 94% of the patients included were men, with a mean age of 68(8.5) years and a mean FEV1% predicted 52 (16). High exposure to gases or fumes was associated with chronic bronchitis, and exposure to mineral dust and gases/fumes was associated with higher scores for symptom perception in the St. George’s questionnaire. No occupational agent was associated with a lower FEV1. High exposure to all occupational agents was associated with better lung diffusion capacity, in long-term quitters. In the subgroup with CT data, patients with emphysema had 18% lower DLCO compared to those without emphysema. Conclusions In our cohort of COPD patients, high exposure to gases or fumes was associated with chronic bronchitis, and high exposure to all occupational agents was consistently associated with better diffusion capacity in long-term quitters. PMID:24516659

Modeling potential occupational inhalation exposures and associated risks of toxic organics from chemical storage tanks used in hydraulic fracturing using AERMOD.

PubMed

Chen, Huan; Carter, Kimberly E

2017-05-01

Various toxic chemicals used in hydraulic fracturing fluids may influence the inherent health risks associated with these operations. This study investigated the possible occupational inhalation exposures and potential risks related to the volatile organic compounds (VOCs) from chemical storage tanks and flowback pits used in hydraulic fracturing. Potential risks were evaluated based on radial distances between 5 m and 180 m from the wells for 23 contaminants with known inhalation reference concentration (RfC) or inhalation unit risks (IUR). Results show that chemicals used in 12.4% of the wells posed a potential acute non-cancer risks for exposure and 0.11% of the wells with may provide chronic non-cancer risks for exposure. Chemicals used in 7.5% of the wells were associated with potential acute cancer risks for exposure. Those chemicals used in 5.8% of the wells may be linked to chronic cancer risks for exposure. While eight organic compounds were associated with acute non-cancer risks for exposure (>1), methanol the major compound in the chemical storage tanks (1.00-45.49) in 7,282 hydraulic fracturing wells. Wells with chemicals additives containing formaldehyde exhibited both acute and chronic cancer risks for exposure with IUR greater than 10 -6 , suggesting formaldehyde was the dominant contributor to both types of risks for exposure in hydraulic fracturing. This study also found that due to other existing on-site emission sources of VOCs and the geographically compounded air concentrations from other surrounding wells, chemical emissions data from storage tanks and flowback pits used in this study were lower than reported concentrations from field measurements where higher occupational inhalation risks for exposure may be expected. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic Nicotine Treatment During Adolescence Attenuates the Effects of Acute Nicotine in Adult Contextual Fear Learning.

PubMed

Holliday, Erica D; Gould, Thomas J

2017-01-01

Adolescent onset of nicotine abuse is correlated with worse chances at successful abstinence in adulthood. One reason for this may be due to enduring learning deficits resulting from nicotine use during adolescence. Previous work has indicated that chronic nicotine administration beginning in late adolescence (PND38) caused learning deficits in contextual fear when tested in adulthood. The purpose of this study was to determine if chronic nicotine treatment during adolescence would alter sensitivity to nicotine's cognitive enhancing properties in adulthood. C57BL/6J mice received saline or chronic nicotine (12.6mg/kg/day) during adolescence (postnatal day 38) or adulthood (postnatal day 54) for a period of 12 days. Following a 30-day protracted abstinence, mice received either an acute injection of saline or nicotine (0.045, 0.18, and 0.36mg/kg) prior to training and testing a mouse model of contextual fear. It was found that chronic nicotine administration in adult mice did not alter sensitivity to acute nicotine following a protracted abstinence. In adolescent mice, chronic nicotine administration disrupted adult learning and decreased sensitivity to acute nicotine in adulthood as only the highest dose tested (0.36mg/kg) was able to enhance contextual fear learning. These results suggest that adolescent nicotine exposure impairs learning in adulthood, which could increase the risk for continued nicotine use in adulthood by requiring administration of higher doses of nicotine to reverse learning impairments caused by adolescent nicotine exposure. Results from this study add to the growing body of literature suggesting chronic nicotine exposure during adolescence leads to impaired learning in adulthood and demonstrates that nicotine exposure during adolescence attenuates the cognitive enhancing effects of acute nicotine in adulthood, which suggests altered cholinergic function. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

PubMed

Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

2015-01-01

Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

Chronic stress disrupts neural coherence between cortico-limbic structures.

PubMed

Oliveira, João Filipe; Dias, Nuno Sérgio; Correia, Mariana; Gama-Pereira, Filipa; Sardinha, Vanessa Morais; Lima, Ana; Oliveira, Ana Filipa; Jacinto, Luís Ricardo; Ferreira, Daniela Silva; Silva, Ana Maria; Reis, Joana Santos; Cerqueira, João José; Sousa, Nuno

2013-01-01

Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP) and the medial prefrontal cortex (mPFC) in rats subjected to short term stress (STS) and chronic unpredictable stress (CUS). CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

PubMed Central

Claussen, Catherine M; Dafny, Nachum

2016-01-01

The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0 mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization were also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals was observed for the 2.5 and 10.0 mg/kg MPD exposed groups. For 2.5 mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0 mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0 mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and oppositely at ED10 MPD rechallenge. While the behaviorally sensitized animals in general increased in their percentage change of firing rats were observed following acute 10.0 mg/kg MPD and the behaviorally sensitized 10.0 mg/kg MPD animals and a robust increase in neuronal firing rates at ED1 and ED10 rechallenge. These results suggest the need to first individually analyze animal behavioral activity, and than to evaluate the neuronal responses to the drug based on the animals behavioral response to chronic MPD exposure. PMID:26101057

Chronic EtOH effects on putative measures of compulsive behavior in mice

PubMed Central

Radke, Anna K.; Jury, Nicholas J.; Kocharian, Adrina; Marcinkiewcz, Catherine A.; Lowery-Gionta, Emily G.; Pleil, Kristen E.; McElligott, Zoe A.; McKlveen, Jessica M.; Kash, Thomas L.; Holmes, Andrew

2015-01-01

Addictions, including alcohol use disorders (AUDs), are characterized by the loss of control over drug seeking and consumption, but the neural circuits and signaling mechanisms responsible for the transition from controlled use to uncontrolled abuse remain incompletely understood. Prior studies have shown that ‘compulsive-like’ behaviors in rodents, e.g., persistent responding for ethanol (EtOH) despite punishment, are increased after chronic exposure to EtOH. The main goal of the current study was to assess the effects of chronic intermittent EtOH (CIE) exposure on multiple, putative measures of compulsive-like EtOH seeking in C57BL/6J mice. Mice were exposed to two or four weekly cycles of CIE and then, post-withdrawal, tested for progressive ratio responding for EtOH, sustained responding during signaled EtOH-unavailability and (footshock) punished-suppression of responding for EtOH. Results showed that mice exposed to CIE exhibited attenuated suppression of EtOH-seeking during punishment, as compared to air-exposed controls. By contrast, CIE exposure affected neither punished food reward-seeking behavior, nor other putative measures of compulsive-like EtOH-seeking. Ex vivo RT-PCR analysis of brain tissue found reduced sensitivity to punished EtOH-seeking after CIE exposure was accompanied by a significant increase in gene expression of the GluN1 and GluN2A subunits of the N-methyl-D-aspartate receptor (NMDAR), specifically in the medial orbitofrontal cortex (mOFC). Moreover, slice electrophysiological analysis revealed increased NMDAR-mediated currents in the mOFC after CIE exposure in test-naïve mice. Collectively, the current findings add to growing body of evidence demonstrating that chronic exposure to EtOH fosters resistance to punished EtOH-seeking in association with adaptations in cortical glutamatergic transmission. PMID:26687341

Persistent modification of Nav1.9 following chronic exposure to insecticides and pyridostigmine bromide.

PubMed

Nutter, Thomas J; Cooper, Brian Y

2014-06-15

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Nav1.8, but increased Kv7 mediated inhibitory currents 8weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Nav1.9 expressed in muscle and vascular nociceptors. During a 60day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Nav1.9, but significant increases in the amplitude of Nav1.9 were observed 8weeks after exposure. Cellular studies, at the 8week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22°C). Acute application of permethrin (10μM) also increased the amplitude of Nav1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Nav1.9 expressed in muscle and vascular nociceptors. The reported increases in Kv7 amplitude may have been an adaptive response to increased Nav1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Nav1.9 and Kv7 could release spontaneous discharge and produce chronic deep tissue pain. Copyright © 2014 Elsevier Inc. All rights reserved.

Multicomponent behavioral treatment for chronic combat-related posttraumatic stress disorder: A randomized controlled trial

PubMed Central

Beidel, Deborah C.; Frueh, B. Christopher; Uhde, Thomas W.; Wong, Nina; Mentrikoski, Janelle M.

2010-01-01

This study examined the efficacy of a multicomponent cognitive-behavioral therapy, Trauma Management Therapy, which combines exposure therapy and social emotional rehabilitation, to exposure therapy only in a group of male combat veterans with chronic posttraumatic stress disorder (PTSD). Thirty-five male Vietnam veterans with PTSD were randomly assigned to receive either Trauma Management Therapy (TMT) or Exposure Therapy Only (EXP). Participants were assessed at pre-treatment, mid-treatment, and post-treatment. Primary clinical outcomes were reduction of PTSD symptoms and improved social emotional functioning. Results indicated that veterans in both conditions showed statistically significant and clinically meaningful reductions in PTSD symptoms from pre- to post-treatment, though consistent with a priori hypotheses there were no group differences on PTSD variables. However, compared to the EXP group, participants in the TMT group showed increased frequency in social activities and greater time spent in social activities. These changes occurred from mid-treatment (after completion of exposure therapy) to post-treatment (after completion of the social emotional rehabilitation component); supporting the hypothesis that TMT alone would result in improved social functioning. Although the TMT group also had a significant decrease in episodes of physical rage, that change occurred prior to introduction of the social emotional component of TMT. This study demonstrates efficacy of exposure therapy for treating the core symptoms of PTSD among combat veterans with a severe and chronic form of this disorder. Moreover, multi-component CBT shows promise for improving social functioning beyond that provided by exposure therapy alone, particularly by increasing social engagement/interpersonal functioning in a cohort of veterans with severe and chronic PTSD. PMID:20951543

Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, Richard L.; Jiang, Yue; Jing, Yi

2011-10-28

Highlights: Black-Right-Pointing-Pointer Chronic exposure to arsenite induces cell proliferation and transformation. Black-Right-Pointing-Pointer Arsenite-induced transformation increases ROS production and downstream signalings. Black-Right-Pointing-Pointer Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. Black-Right-Pointing-Pointer Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidencemore » suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.« less

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels.

PubMed

Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

2017-04-10

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl₂ (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABA A ) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism.

Individual Differences in Initial Sensitivity and Acute Tolerance Predict Patterns of Chronic Drug Tolerance to Nitrous-Oxide-Induced Hypothermia in Rats

PubMed Central

Ramsay, Douglas S.; Kaiyala, Karl J.; Leroux, Brian G.; Woods, Stephen C.

2006-01-01

Rationale: A preventive strategy for drug addiction would benefit from being able to identify vulnerable individuals. Understanding how an individual responds during an initial drug exposure may be useful for predicting how that individual will respond to repeated drug administrations. Objectives: This study investigated whether individual differences in initial drug sensitivity and acute tolerance can predict how chronic tolerance develops. Methods: During an initial 3-h administration of 60% nitrous oxide (N2O), male Long-Evans rats were screened for N2O’s hypothermic effect into subsets based on being initially insensitive (II), sensitive with acute tolerance (AT), or sensitive with no intrasessional recovery (NR). Animals in each individual difference category were randomly assigned to receive six 90-min exposures of either 60% N2O or placebo gas. Core temperature was measured telemetrically. Results: Rats that exhibited a comparable degree of hypothermia during an initial N2O exposure, but differed in acute tolerance development, developed different patterns of chronic tolerance. Specifically, the NR group did not become fully tolerant over repeated N2O exposures while the AT group developed an initial hyperthermia followed by a return of core temperature to control levels indicative of full tolerance development. By the second N2O exposure, the II group breathing N2O became hyperthermic relative to the placebo control group and this hyperthermia persisted throughout the multiple N2O exposures. Conclusions: Individual differences in initial drug sensitivity and acute tolerance development predict different patterns of chronic tolerance. The hypothesis is suggested that individual differences in opponent adaptive responses may mediate this relationship. PMID:15778887

Proteome-wide changes in primary skin keratinocytes exposed to diesel particulate extract-A role for antioxidants in skin health.

PubMed

Rajagopalan, Pavithra; Jain, Ankit P; Nanjappa, Vishalakshi; Patel, Krishna; Mangalaparthi, Kiran K; Babu, Niraj; Cavusoglu, Nükhet; Roy, Nita; Soeur, Jeremie; Breton, Lionel; Pandey, Akhilesh; Gowda, Harsha; Chatterjee, Aditi; Misra, Namita

2018-05-21

Skin acts as a protective barrier against direct contact with pollutants but inhalation and systemic exposure have indirect effect on keratinocytes. Exposure to diesel exhaust has been linked to increased oxidative stress. To investigate global proteomic alterations in diesel particulate extract (DPE)/its vapor exposed skin keratinocytes. We employed Tandem Mass Tag (TMT)-based proteomics to study effect of DPE/DPE vapor on primary skin keratinocytes. We observed an increased expression of oxidative stress response protein NRF2, upon chronic exposure of primary keratinocytes to DPE/its vapor which includes volatile components such as polycyclic aromatic hydrocarbons (PAHs). Mass spectrometry-based quantitative proteomics led to identification 4490 proteins of which 201 and 374 proteins were significantly dysregulated (≥1.5 fold, p ≤ 0.05) in each condition, respectively. Proteins involved in cellular processes such as cornification (cornifin A), wound healing (antileukoproteinase) and differentiation (suprabasin) were significantly downregulated in primary keratinocytes exposed to DPE/DPE vapor. These results were corroborated in 3D skin models chronically exposed to DPE/DPE vapor. Bioinformatics analyses indicate that DPE and its vapor affect distinct molecular processes in skin keratinocytes. Components of mitochondrial oxidative phosphorylation machinery were seen to be exclusively overexpressed upon chronic DPE vapor exposure. In addition, treatment with an antioxidant like vitamin E partially restores expression of proteins altered upon exposure to DPE/DPE vapor. Our study highlights distinct adverse effects of chronic exposure to DPE/DPE vapor on skin keratinocytes and the potential role of vitamin E in alleviating adverse effects of environmental pollution. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chronic warm exposure impairs growth performance and reduces thermal safety margins in the common triplefin fish (Forsterygion lapillum).

PubMed

McArley, Tristan J; Hickey, Anthony J R; Herbert, Neill A

2017-10-01

Intertidal fish species face gradual chronic changes in temperature and greater extremes of acute thermal exposure through climate-induced warming. As sea temperatures rise, it has been proposed that whole-animal performance will be impaired through oxygen and capacity limited thermal tolerance [OCLTT; reduced aerobic metabolic scope (MS)] and, on acute exposure to high temperatures, thermal safety margins may be reduced because of constrained acclimation capacity of upper thermal limits. Using the New Zealand triplefin fish ( Forsterygion lapillum ), this study addressed how performance in terms of growth and metabolism (MS) and upper thermal tolerance limits would be affected by chronic exposure to elevated temperature. Growth was measured in fish acclimated (12 weeks) to present and predicted future temperatures and metabolic rates were then determined in fish at acclimation temperatures and with acute thermal ramping. In agreement with the OCLTT hypothesis, chronic exposure to elevated temperature significantly reduced growth performance and MS. However, despite the prospect of impaired growth performance under warmer future summertime conditions, an annual growth model revealed that elevated temperatures may only shift the timing of high growth potential and not the overall annual growth rate. While the upper thermal tolerance (i.e. critical thermal maxima) increased with exposure to warmer temperatures and was associated with depressed metabolic rates during acute thermal ramping, upper thermal tolerance did not differ between present and predicted future summertime temperatures. This suggests that warming may progressively decrease thermal safety margins for hardy generalist species and could limit the available habitat range of intertidal populations. © 2017. Published by The Company of Biologists Ltd.

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels

PubMed Central

Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

2017-01-01

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism. PMID:28394286

Estimating Air-Manganese Exposures in Two Ohio Towns

EPA Science Inventory

Manganese (Mn), a nutrient required for normal metabolic function, is also a persistent air pollutant and a known neurotoxin at high concentrations. Elevated exposures can result in a number of motor and cognitive deficits. Quantifying chronic personal exposures in residential po...

Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Full Life-Cycle Exposure to Bedded Sediments

DTIC Science & Technology

1993-06-01

COMMUNITY ENZYME OSMOREGULATION ENERGY FLOW DNA/RNA BEHAVIOR NUTRIENT CYCLING END POINT MEMBRANES METABOLISM INTRASPECIFIC HISTOPATHOLOGY SURVIVAL...Miscellaneous Paper D-93-2AD-A268 207 June 1993 US Army Corps of Engineers Waterways Experiment Station Long-Term Effects of Dredging Operations...Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Full Life-Cycle Exposure to Bedded Sediments by

Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

DTIC Science & Technology

2013-10-01

collection in underway. 15. SUBJECT TERMS Spinal Cord Injury, Immunogenetics, Chronic pain, Opioids 16. SECURITY CLASSIFICATION OF: 17...prototypic opioid , morphine, is capable of TLR4-mediated proinflammation6-8 . As such, exposure to morphine at the time of injury may result in...fashion to the spinal cord injury and/or to experience inflammation in response to opioid exposure. Critically, this genetic variability may

Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

DTIC Science & Technology

2014-10-01

collection in underway. 15. SUBJECT TERMS Spinal Cord Injury, Immunogenetics, Chronic pain, Opioids 16. SECURITY CLASSIFICATION OF: 17...The prototypic opioid , morphine, is capable of TLR4-mediated proinflammation6-8. As such, exposure to morphine at the time of injury may result in...proinflammatory fashion to the spinal cord injury, and/or to experience inflammation in response to opioid exposure. Critically, this genetic variability

Prospective assessment of chronic multisymptom illness reporting possibly associated with open-air burn pit smoke exposure in Iraq.

PubMed

Powell, Teresa M; Smith, Tyler C; Jacobson, Isabel G; Boyko, Edward J; Hooper, Tomoko I; Gackstetter, Gary D; Phillips, Christopher J; Smith, Besa

2012-06-01

To investigate the relationship between chronic multisymptom illness (CMI) and possible exposure to an open-air burn pit at three selected bases among those deployed to operations in Iraq and Afghanistan. Chronic multisymptom illness (reporting at least one symptom in at least two of the following symptom constructs: general fatigue; mood and cognition problems; and musculoskeletal discomfort) was assessed, differentiating by potential burn pit exposure, among deployers who completed 2004 and 2007 Millennium Cohort questionnaires. More than 21,000 Cohort participants were deployed in support of the current operations, including more than 3000 participants with at least one deployment within a 3-mile radius of a documented burn pit. After adjusting for covariates, no elevated risk of CMI was observed among those exposed. There was no increase in CMI symptom reporting in those deployed to three selected bases with documented burn pits compared with other deployers.

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

PubMed

Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic Effects of Fluoride Exposure on Growth, Metamorphosis, and Skeleton Development in Bufo gargarizans Larvae.

PubMed

Chai, Lihong; Wang, Hongyuan; Zhao, Hongfeng; Dong, Suiming

2017-04-01

Bufo gargarizans tadpoles were chronically exposed to waterborne fluoride at measured concentrations ranging from 0.4 to 61.2 mg F - /L for 70 days from Gosner stage 26 to completion of metamorphosis. The chronic exposure caused a concentration-dependent mortality in all tested fluoride concentrations. Total length, snout-to-vent length (SVL), body mass, and developmental stage of tadpoles were significantly inhibited at 42.6 mg F - /L. In addition, significant metamorphic delay and increase in size at completion of metamorphosis occurred after exposure to 19.8 mg F - /L. Moreover, 19.8 mg F - /L suppressed the bone mineralization of larvae at completion of metamorphosis. However, the bone mineralization could be enhanced by 4.1 mg F - /L. In conclusion, our results suggested that the presence of high concentrations of fluoride could increase mortality risk, delay metamorphosis, and suppress skeletal ossification in B. gargarizans larvae.

[Chronic kidney disease in Mexico and its relation with heavy metals].

PubMed

Chávez-Gómez, Nancy Libertad; Cabello-López, Alejandro; Gopar-Nieto, Rodrigo; Aguilar-Madrid, Guadalupe; Marin-López, Kennia Stephanie; Aceves-Valdez, Maricruz; Jiménez-Ramírez, Carmina; Cruz-Angulo, María del Carmen; Juárez-Pérez, Cuauhtémoc Arturo

2017-01-01

Chronic kidney disease (CKD) is a public health problem in Mexico, causing 25% of deaths related to diabetes mellitus (DM) and 28% related to hypertensive heart disease. In 2008 CKD reached the highest incidence of end-stage renal disease in the world. Diabetes mellitus is the main risk factor associated with CKD in Mexican population; however, heavy metals such as lead, arsenic, cadmium and mercury have been associated to nephropathies. In Mexico there are still high levels of these compounds in occupational and environmental settings; therefore, chronic exposures to these metals persist. In this review we approach to the main mechanisms of action of these metals in the body and its renal effects, as well as information about the sources of exposure to these chemical risks, the relationship between exposure to heavy metals and CKD, coupled with the economic and social consequences of this disease.

Pulmonary function adaptation to ozone in subjects with chronic bronchitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulle, T.J.; Milman, J.H.; Sauder, L.R.

Twenty smokers with chronic bronchitis were exposed to 0.41 ppm ozone for 3 hr-day for 5 consecutive days and reexposed 4 days later to determine (1) if they are sensitive to ozone, (2) if they adapt, and (3) if the adaptation lasts longer than 4 days. There were significant decrements in forced vital capacity (FVC) and forced expiratory volume in 3 sec (FEV/sub 3/) on the first day of the 5-day repeated exposures and also on reexposure 4 days following cessation of the sequential exposures. Symptoms experienced were mild and did not predominate on any exposure days. These results suggestmore » that individuals with chronic bronchitis adapt rapidly to ozone and lose this adaptive phenomenon within 4 days. The small decreases seen in FVC and FEV/sub 3/ ( less than or equal to 3%) appear to impose no more than minimal limitations on their daily activities.« less

Pulmonary function adaptation to ozone in subjects with chronic bronchitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulle, T.J.; Milman, J.H.; Sauder, L.R.

Twenty smokers with chronic bronchitis were exposed to 0.41 ppm ozone for 3 hr-day for 5 consecutive days and reexposed 4 days later to determine (1) if they are sensitive to ozone, (2) if they adapt, and (3) if the adaptation lasts longer than 4 days. There were significant decrements in forced vital capacity (FVC) and forced expiratory volume in 3 sec (FEV3) on the first day of the 5-day repeated exposures and also on reexposure 4 days following cessation of the sequential exposures. Symptoms experienced were mild and did not predominate on any exposure days. These results suggest thatmore » individuals with chronic bronchitis adapt rapidly to ozone and lose the adaptive phenomenon within 4 days. The small decreases seen in FVC and FEV3 appear to impose no more than minimal limitations on their daily activities.« less

An high-performance liquid chromatographic method for the simultaneous analysis of acetylcarnitine taurinate, carnosine, asparagine and potassium aspartate and for the analysis of phosphoserine in alimentary supplements.

PubMed

Gatti, R; Andreatta, P; Boschetti, S

2013-07-12

A RP-HPLC method with pre-column derivatization was developed and validated for the simultaneous quantification of carnosine (Carn), acetylcarnitine taurinate (AC-Tau), asparagine (Asn), potassium aspartate (Asp) and for the determination of phosphoserine (p-Ser) in new and commercial alimentary supplements. The effect of complex matrices was evaluated by the study of the amino acid derivatization reaction with 2,4-dinitrofluorobenzene (DNFB) both in standard and placebo solutions. The reaction was carried out for 20 min at 70 °C in alkaline medium (pH10) for p-Ser analysis, whereas for 60 min in the case of Carn, AC-Tau, Asn and Asp analysis. The adducts have been separated on a Discovery RP Amide C16 (250 mm×4.6mm, i.d.) column using a mobile phase consisting of acetonitrile (ACN) and triethylammonium (TEA) phosphate buffer (pH 3, 0.05 M) under gradient elution conditions at a flow-rate of 0.8 mL/min. Detection was set at λ=360 nm. The validation parameters such as linearity, sensitivity, accuracy, precision and specificity were found to be highly satisfactory. Linear responses were observed by placebo solutions (determination coefficient ≤0.9996). Intra-day precision (relative standard deviation, RSD) was ≤1.06% for corrected peak area and ≤0.99% for retention times (tR) without significant differences between intra- and inter-day data. Recovery studies showed good results for all examined compounds (from 97.7% to 101.5%) with RSD ranging from 0.5% to 1.3%). The high stability of derivatized compound solutions at room temperature means an undoubted advantage of the method allowing the simultaneous preparation of a large number of samples and consecutive chromatographic analyses by the use of an autosampler. The developed method can be considered suitable for the quality control of new and commercial products. Copyright © 2013 Elsevier B.V. All rights reserved.

NEUROCHEMICAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS IN RATS.

EPA Science Inventory

Lots of information is available surrounding the acute toxicity of anticholinesterase pesticides, but these have been very few detailed studies on the chronic effects of these pesticides. Humans are exposed on a chronic basis and some humans believe that have been affected advers...

Chronic air pollution and social deprivation as modifiers of the association between high temperature and daily mortality

PubMed Central

2014-01-01

Background Heat and air pollution are both associated with increases in mortality. However, the interactive effect of temperature and air pollution on mortality remains unsettled. Similarly, the relationship between air pollution, air temperature, and social deprivation has never been explored. Methods We used daily mortality data from 2004 to 2009, daily mean temperature variables and relative humidity, for Paris, France. Estimates of chronic exposure to air pollution and social deprivation at a small spatial scale were calculated and split into three strata. We developed a stratified Poisson regression models to assess daily temperature and mortality associations, and tested the heterogeneity of the regression coefficients of the different strata. Deaths due to ambient temperature were calculated from attributable fractions and mortality rates were estimated. Results We found that chronic air pollution exposure and social deprivation are effect modifiers of the association between daily temperature and mortality. We found a potential interactive effect between social deprivation and chronic exposure with regards to air pollution in the mortality-temperature relationship. Conclusion Our results may have implications in considering chronically polluted areas as vulnerable in heat action plans and in the long-term measures to reduce the burden of heat stress especially in the context of climate change. PMID:24941876

Chronic air pollution and social deprivation as modifiers of the association between high temperature and daily mortality.

PubMed

Benmarhnia, Tarik; Oulhote, Youssef; Petit, Claire; Lapostolle, Annabelle; Chauvin, Pierre; Zmirou-Navier, Denis; Deguen, Séverine

2014-06-18

Heat and air pollution are both associated with increases in mortality. However, the interactive effect of temperature and air pollution on mortality remains unsettled. Similarly, the relationship between air pollution, air temperature, and social deprivation has never been explored. We used daily mortality data from 2004 to 2009, daily mean temperature variables and relative humidity, for Paris, France. Estimates of chronic exposure to air pollution and social deprivation at a small spatial scale were calculated and split into three strata. We developed a stratified Poisson regression models to assess daily temperature and mortality associations, and tested the heterogeneity of the regression coefficients of the different strata. Deaths due to ambient temperature were calculated from attributable fractions and mortality rates were estimated. We found that chronic air pollution exposure and social deprivation are effect modifiers of the association between daily temperature and mortality. We found a potential interactive effect between social deprivation and chronic exposure with regards to air pollution in the mortality-temperature relationship. Our results may have implications in considering chronically polluted areas as vulnerable in heat action plans and in the long-term measures to reduce the burden of heat stress especially in the context of climate change.

Comparison of molecular marker expression in early zebrafish brain development following chronic ethanol or morpholino treatment.

PubMed

Zhang, Chengjin; Boa-Amponsem, Oswald; Cole, Gregory J

2017-08-01

This study was undertaken to ascertain whether defined markers of early zebrafish brain development are affected by chronic ethanol exposure or morpholino knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors, four signaling molecules that are suggested to be ethanol sensitive. Zebrafish embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha, aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early brain development. Our results showed that pax6a mRNA expression was decreased in eye, forebrain, and hindbrain of both chronic ethanol exposed and select MO treatments. Epha4a expression in rhombomere R1 boundary was decreased in chronic ethanol exposure and aldh1a3 morphants, lost in fgf8a morphants, but largely unaffected in agrin and shha morphants. Ectopic pax6a and epha4a expression in midbrain was only found in fgf8a morphants. These results suggest that while chronic ethanol induces obvious morphological change in brain architecture, many molecular markers of these brain structures are relatively unaffected by ethanol exposure.

Effects of episodic acidification on Atlantic salmon (Salmo salar) smolts

USGS Publications Warehouse

Magee, J.A.; Obedzinski, M.; McCormick, S.D.; Kocik, J.F.

2003-01-01

The effect of episodic acidification on Atlantic salmon (Salmo salar) smolt physiology and survival in fresh water (FW) and seawater (SW) was investigated. Smolts were held in either ambient (control, pH 6.0-6.6), acidified (chronic, pH 4.4-6.1), or episodically acidified (episodic, pH reduction from control levels to pH ???5.2 for 48 h once weekly) river water for 31 days and then transferred to 34??? SW. Smolts fed little while in acidified conditions and chronic smolts did not grow in length or weight. In FW, chronic smolts experienced increases in hematocrit and plasma potassium and reductions in plasma sodium and chloride. Upon transfer to SW, chronic and episodic smolts experienced reductions in hematocrit, increases in plasma sodium, chloride, and potassium levels, and suffered mortalities. Gill Na+,K+-ATPase and citrate synthase activities were reduced by exposure to acid. For most parameters, the effect of episodic acid exposure was less than that of chronic acidification. Exposure to acidic conditions, even when short in duration and followed by a 30-h recovery period in suitable water (pH 6.5), led to a 35% mortality of smolts upon transfer to SW. This study highlights the importance of measuring and assessing sublethal stresses in FW and their ultimate effects in marine ecosystems.

Chronic low-level arsenite exposure through drinking water increases blood pressure and promotes concentric left ventricular hypertrophy in female mice.

PubMed

Sanchez-Soria, Pablo; Broka, Derrick; Monks, Sarah L; Camenisch, Todd D

2012-04-01

Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding of how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressure. Echocardiographic analyses as well as histological assessment show concentric left ventricular hypertrophy, a primary cardiac manifestation of chronic hypertension. Live imaging by echocardiography shows a 43% increase in left ventricular mass in arsenic-treated animals. Relative wall thickness (RWT) was calculated showing that all the arsenic-exposed animals show an RWT greater than 0.45, indicating concentric hypertrophy. Importantly, left ventricular hypertrophy, although often associated with chronic hypertension, is an independent risk factor for cardiovascular-related mortalities. These results suggest that chronic low-level arsenite exposure promotes the development of hypertension and the comorbidity of concentric hypertrophy.

Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA antagonist neurotoxicity.

PubMed

Farber, Nuri B; Nemmers, Brian; Noguchi, Kevin K

2006-09-15

Antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor, most likely by producing disinhibtion in complex circuits, acutely produce psychosis and cognitive disturbances in humans, and neurotoxicity in rodents. Studies examining NMDA Receptor Hypofunction (NRHypo) neurotoxicity in animals, therefore, may provide insights into the pathophysiology of psychotic disorders. Dopaminergic D2 and/or D3 agents can modify psychosis over days to weeks, suggesting involvement of these transmitter system(s). We studied the ability of D2/D3 agonists and antagonists to modify NRHypo neurotoxicity both after a one-time acute exposure and after chronic daily exposure. Here we report that D2/D3 dopamine agonists, probably via D3 receptors, prevent NRHypo neurotoxicity when given acutely. The protective effect with D2/D3 agonists is not seen after chronic daily dosing. In contrast, the antipsychotic haloperidol does not affect NRHypo neurotoxicity when given acutely at D2/D3 doses. However, after chronic daily dosing of 1, 3, or 5 weeks, haloperidol does prevent NRHypo neurotoxicity with longer durations producing greater protection. Understanding the changes that occur in the NRHypo circuit after chronic exposure to dopaminergic agents could provide important clues into the pathophysiology of psychotic disorders.

An ecological risk assessment of the acute and chronic toxicity of the herbicide picloram to the threatened bull trout (salvelinus confluentus) and the rainbow trout (onchorhyncus mykiss)

USGS Publications Warehouse

Fairchild, J.F.; Feltz, K.P.; Sappington, L.C.; Allert, A.L.; Nelson, K.J.; Valle, J.

2009-01-01

We conducted acute and chronic toxicity studies of the effects of picloram acid on the threatened bull trout (Salvelinus confluentus) and the standard coldwater surrogate rainbow trout (Oncorhynchus mykiss). Juvenile fish were chronically exposed for 30 days in a proportional flow-through diluter to measured concentrations of 0, 0.30, 0.60, 1.18, 2.37, and 4.75 mg/L picloram. No mortality of either species was observed at the highest concentration. Bull trout were twofold more sensitive to picloram (30-day maximum acceptable toxic concentration of 0.80 mg/L) compared to rainbow trout (30-day maximum acceptable toxic concentration of 1.67 mg/L) based on the endpoint of growth. Picloram was acutely toxic to rainbow trout at 36 mg/L (96-h ALC50). The acute:chronic ratio for rainbow trout exposed to picloram was 22. The chronic toxicity of picloram was compared to modeled and measured environmental exposure concentrations (EECs) using a four-tiered system. The Tier 1, worst-case exposure estimate, based on a direct application of the current maximum use rate (1.1 kg/ha picloram) to a standardized aquatic ecosystem (water body of 1-ha area and 1-m depth), resulted in an EEC of 0.73 mg/L picloram and chronic risk quotients of 0.91 and 0.44 for bull trout and rainbow trout, respectively. Higher-tiered exposure estimates reduced chronic risk quotients 10-fold. Results of this study indicate that picloram, if properly applied according to the manufacturer's label, poses little risk to the threatened bull trout or rainbow trout in northwestern rangeland environments on either an acute or a chronic basis. ?? 2008 Springer Science+Business Media, LLC.

Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study.

PubMed

Mocroft, Amanda; Lundgren, Jens D; Ross, Michael; Fux, Christoph A; Reiss, Peter; Moranne, Olivier; Morlat, Philippe; Monforte, Antonella d'Arminio; Kirk, Ole; Ryom, Lene

2016-01-01

Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir. In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored. The Highly Active Antiretroviral Therapy Oversight Committee. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytogenetic damages in peripheral blood of monkey lymphocytes under simulation of cosmonauts irradiation.

NASA Astrophysics Data System (ADS)

Petrov, Vladislav; Ivanov, Alexandr; Barteneva, Svetlana; Snigiryeva, Galina; Shafirkin, Alexandr

Earth modeling of crewmember exposure should be performed for correct estimating radiation hazard during the flight. Such modeling was planned in a monkey experiment for investigating consequences of exposure to a man during an interplanetary flight. It should reflect a chronic impact of galactic cosmic rays and acute and fractional irradiation specified for solar cosmic rays and radiation belts respectively. Due to the difficulty of modeling a chronic impact with the help of a charged particles accelerator it can be used the gamma source. While irradiating big animal groups during a long-term period of time it is preferably to replace chronic irradiation by an equal fractional one. In this case the chosen characteristics of fractional irradiation should ensure the appearances of radiobiological consequences equal to the ones caused by the modeled chronic exposure. So for developing an exposure scheme in the monkey experiment (with Macaca -Rhesus) the model of the acting residual dose, that takes into account repair and recovery processes in the exposed body was used. The total dose value was in the limits from 2.32 Gy up to 3.5 Gy depending on the exposure character. The acting residual dose in all versions of exposure was 2.0 Gy for every monkey. While performing the experiment all the requirements of bioethics for the work with animals were observed. The objects of interest were genomic damages in lymphocytes of monkey's peripheral blood. The data about the CAF during the exposure and at various time moments after exposure particularly directly after the completion of chronicle and fractional irradiation were analyzed. CAF -dose of acute single gamma-irradiation in the range 0 -1.5Gy relationship (calibration curve) was defined in vitro. In addition the rate of the aberrant cells elimination within three months after the irradiation completion was estimated. On the basis of the obtained CAF data we performed verification of applicability of cytogenetic analysis for estimating the monkey gamma -dose exposure in the experiment It was obtained that this method permits to estimate the acting residual dose with accuracy of 30

Taste responses to monosodium glutamate after alcohol exposure.

PubMed

Wrobel, Elzbieta; Skrok-Wolska, Dominika; Ziolkowski, Marcin; Korkosz, Agnieszka; Habrat, Boguslaw; Woronowicz, Bohdan; Kukwa, Andrzej; Kostowski, Wojciech; Bienkowski, Przemyslaw; Scinska, Anna

2005-01-01

The aim of the present study was to evaluate the effects of acute and chronic exposure to alcohol on taste responses to a prototypic umami substance, monosodium glutamate (MSG). The rated intensity and pleasantness of MSG taste (0.03-10.0%) was compared in chronic male alcoholics (n = 35) and control subjects (n = 25). In a separate experiment, the effects of acute exposure of the oral mucosa to ethanol rinse (0.5-4.0%) on MSG taste (0.3-3.0%) were studied in 10 social drinkers. The alcoholic and control group did not differ in terms of the rated intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (P < 0.01) higher, i.e. worse, in the alcohol-dependent subjects. The difference remained significant after controlling for between-group differences in cigarette smoking and coffee drinking. Rinsing with ethanol did not alter either intensity or pleasantness of MSG taste in social drinkers. The present results suggest that: (i) neither acute nor chronic alcohol exposure modifies taste responses to MSG; (ii) alcohol dependence may be associated with deficit in threshold taste reactivity, as assessed by electrogustometry.