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Sample records for accidental chronic exposure

  1. Epidemiology of accidental radiation exposures.

    PubMed Central

    Cardis, E

    1996-01-01

    Much of the information on the health effects of radiation exposure available to date comes from long-term studies of the atomic bombings in Hiroshima and Nagasaki. Accidental exposures, such as those resulting from the Chernobyl and Kyshtym accidents, have as yet provided little information concerning health effects of ionizing radiation. This paper will present the current state of our knowledge concerning radiation effects, review major large-scale accidental radiation exposures, and discuss information that could be obtained from studies of accidental exposures and the types of studies that are needed. PMID:8781398

  2. Epidemiology of accidental radiation exposures.

    PubMed

    Cardis, E

    1996-05-01

    Much of the information on the health effects of radiation exposure available to date comes from long-term studies of the atomic bombings in Hiroshima and Nagasaki. Accidental exposures, such as those resulting from the Chernobyl and Kyshtym accidents, have as yet provided little information concerning health effects of ionizing radiation. This paper will present the current state of our knowledge concerning radiation effects, review major large-scale accidental radiation exposures, and discuss information that could be obtained from studies of accidental exposures and the types of studies that are needed.

  3. Chronic or accidental exposure of oysters to norovirus: is there any difference in contamination?

    PubMed

    Ventrone, Iole; Schaeffer, Julien; Ollivier, Joanna; Parnaudeau, Sylvain; Pepe, Tiziana; Le Pendu, Jacques; Le Guyader, Françoise S

    2013-03-01

    Bivalve molluscan shellfish such as oysters may be contaminated by human pathogens. Currently, the primary pathogens associated with shellfish-related outbreaks are noroviruses. This study was conducted to improve understanding of oyster bioaccumulation when oysters were exposed to daily contamination or one accidental contamination event, i.e., different modes of contamination. Oysters were contaminated with two representative strains of norovirus (GI.1 and GII.3) and then analyzed with real-time reverse transcription PCR. Exposure to a repeated virus dose for 9 days (mimicking a growing area subjected to frequent sewage contamination) led to an additive accumulation that was not significantly different from that obtained when the same total dose of virus was added all at once (as may happen after accidental sewage discharge). Similarly, bioaccumulation tests performed with mixed strains revealed additive accumulation of both viruses. Depuration may not be efficient for eliminating viruses; therefore, to prevent contaminated shellfish from being put onto the market, continuous sanitary monitoring must be considered. All climatic events or sewage failures occurring in production areas must be recorded, because repeated low-dose exposure or abrupt events may lead to similar levels of accumulation. This study contributes to an understanding of norovirus accumulation in oysters and provides suggestions for risk management strategies.

  4. Epidemiology of accidental radiation exposures

    SciTech Connect

    Cardis, E.

    1996-05-01

    Much of the information on the health effects of radiation exposure available to date comes from long-term studies of the atomic bombings in Hiroshima and Nagasaki. Accidental exposures, such as those resulting from the Chernobyl and Kyshtym accidents, have as yet provided little information concerning health effects of ionizing radiation. This paper will present the current state of our knowledge concerning radiation effects, review major large-scale accidental exposures and the types of studies that are needed. 64 refs., 3 tabs.

  5. Chromosome Damage Caused by Accidental Chronic Whole-Body Gamma Radiation Exposure in Thailand

    PubMed Central

    Dolling, J.; Lavoie, J.; Mitchel, R. E. J.; Boreham, D. R.

    2015-01-01

    In February 2000, a radiation incident involving a medical 60Co source occurred in a metal scrapyard in Thailand. Several individuals were suspected to have received chronic or fractionated exposures ranging from a few mGy to a several Gy. Using fluorescence in situ hybridization to paint chromosomes, we determined the frequencies of chromosome aberrations in peripheral blood lymphocytes of 13 people who entered the scrapyard, 3 people who involved in recovering the source, and 9 nearby residents. Aberration frequencies greater than controls were observed in 13 of the donors at 3 months postexposure. The predominant form of aberration observed was simple, complete, symmetrical translocations. An approximate 50% decrease in these aberrations and in total color junctions was observed in 7 donors resampled at 16 months postexposure. Although high, acute exposures are known to have detrimental effects, the biological consequences of chronic, low dose-rate radiation exposures are unclear. Thirteen of the donors had elevated aberration frequencies, and 6 also had symptoms of acute radiation syndrome. If there are any long-term health consequences of this incident, it will most likely occur among this group of individuals. The consequences for the remaining donors, who presumably received lower total doses delivered at lower dose rates, are less clear. PMID:26740811

  6. [Management of accidental internal exposure].

    PubMed

    Fatome, M

    1994-11-01

    Radionucleides can penetrate into the body via the lung, the digestive tract, wounds and sometimes through healthy skin. Once they have penetrated the body, they can either remain localized at the site of entry or be rapidly metabolized. The risk is late effects. Radioelements must be eliminated as rapidly as possible decreasing the exposure proportionally. The effectiveness of the treatment depends on early institution. Nevertheless, emergency intensive care or surgery may be required. As soon as possible, explorations must be carried out to evaluate the level of contamination (human spectrometry, radiotoxicological examinations) and to start treatment. Modalities include non-specific techniques (lavage, insolubilization, laxatives) and specific techniques such as complexation or isotopic dilution (iodine for iodine, Prussian blue for cesium, DTPA for plutonium, Diamox or sodium bicarbonate for uranium). Surgical cleaning of wounds and burns is an excellent means of decontamination. External contamination is often associated. Further contamination must be prevented immediately.

  7. [Cutaneous radiation syndrome after accidental skin exposure to ionizing radiation].

    PubMed

    Peter, R U

    2013-12-01

    Accidental exposure of the human skin to single doses of ionizing radiation greater than 3 Gy results in a distinct clinical picture, which is characterized by a transient and faint erythema after a few hours, then followed by severe erythema, blistering and necrosis. Depending on severity of damage, the latter generally occurs 10-30 days after exposure, but in severe cases may appear within 48 hrs. Between three and 24 months after exposure, epidermal atrophy combined with progressive dermal and subcutaneous fibrosis is the predominant clinical feature. Even years and decades after exposure, atrophy of epidermis, sweat and sebaceous glands; telangiectases; and dermal and subcutaneous fibrosis may be found and even continue to progress. For this distinct pattern of deterministic effects following cutaneous accidental radiation exposure the term "cutaneous radiation syndrome (CRS)" was coined in 1993 and has been accepted by all international authorities including IAEA and WHO since 2000. In contrast to the classical concept that inhibition of epidermal stem cell proliferation accounts for the clinical symptomatology, research of the last three decades has demonstrated the additional crucial role of inflammatory processes in the etiology of both acute and chronic sequelae of the CRS. Therefore, therapeutic approaches should include topical and systemic anti-inflammatory measures at the earliest conceivable point, and should be maintained throughout the acute and subacute stages, as this reduces the need for surgical intervention, once necrosis has occurred. If surgical intervention is planned, it should be executed with a conservative approach; no safety margins are needed. Antifibrotic measures in the chronic stage should address the chronic inflammatory nature of this process, in which over-expression TGF beta-1 may be a target for therapeutic intervention. Life-long follow-up often is required for management of delayed effects and for early detection of secondary

  8. Quick management of accidental tritium exposure cases.

    PubMed

    Singh, Vishwanath P; Badiger, N M; Managanvi, S S; Bhat, H R

    2012-07-01

    Removal half-life (RHL) of tritium is one of the best means for optimising medical treatment, reduction of committed effective dose (CED) and quick/easy handling of a large group of workers for medical treatment reference. The removal of tritium from the body depends on age, temperature, relative humidity and daily rainfall; so tritium removal rate, its follow-up and proper data analysis and recording are the best techniques for management of accidental acute tritium exposed cases. The decision of referring for medical treatment or medical intervention (MI) would be based on workers' tritium RHL history taken from their bodies at the facilities. The workers with tritium intake up to 1 ALI shall not be considered for medical treatment as it is a derived limit of annual total effective dose. The short-term MI may be considered for tritium intake of 1-10 ALI; however, if the results show intake ≥100 ALI, extended strong medical/therapeutic intervention may be recommended based on the severity of exposure for maximum CED reduction requirements and annual total effective dose limit. The methodology is very useful for pressurized heavy water reactors (PHWRs) which are mainly operated by Canada and India and future fusion reactor technologies. Proper management will optimise the cases for medical treatment and enhance public acceptance of nuclear fission and fusion reactor technologies.

  9. Mitigation of Lung Injury after Accidental Exposure to Radiation

    PubMed Central

    Mahmood, J.; Jelveh, S.; Calveley, V.; Zaidi, A.; Doctrow, S. R.; Hill, R. P.

    2011-01-01

    There is a serious need to develop effective mitigators against accidental radiation exposures. In radiation accidents, many people may receive nonuniform whole-body or partial-body irradiation. The lung is one of the more radiosensitive organs, demonstrating pneumonitis and fibrosis that are believed to develop at least partially because of radiation-induced chronic inflammation. Here we addressed the crucial questions of how damage to the lung can be mitigated and whether the response is affected by irradiation to the rest of the body. We examined the widely used dietary supplement genistein given at two dietary levels (750 or 3750 mg/kg) to Fischer rats irradiated with 12 Gy to the lung or 8 Gy to the lung + 4 Gy to the whole body excluding the head and tail (whole torso). We found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation. The higher dose of genistein showed no greater beneficial effect. Combined lung and whole-torso irradiation caused more lung-related severe morbidity resulting in euthanasia of the animals than lung irradiation alone. PMID:22013884

  10. Avoiding accidental exposure to intravenous cytotoxic drugs.

    PubMed

    Meade, Elizabeth

    Many cytotoxic drugs have been shown to be mutagenic, teratogenic and carcinogenic with second malignancies known to be associated with several specific cancer drugs. Occupational exposure to cytotoxic drugs presents a signification danger to healthcare staff and unwarranted handling of these drugs should be avoided. Guidelines have been established for the safe handling of hazardous drugs but not all professionals are adhering to these recommendations. Recent environmental studies have demonstrated measurable drug contamination on surfaces even when recommended guidelines are followed. It is therefore imperative that healthcare workers are aware of the potential hazards of antineoplastic agents and employ the recommended precautions to minimise exposure. This article outlines the potential risks associated with exposure to cytotoxic drugs for healthcare staff. The safe-handling precautions required in the storage, preparation, transport, administration and waste disposal of cytotoxic drugs are presented.

  11. Food allergy: practical approach on education and accidental exposure prevention.

    PubMed

    Pádua, I; Moreira, A; Moreira, P; Barros, R

    2016-09-01

    Food allergies are a growing problem and currently the primary treatment of food allergy is avoidance of culprit foods. However, given the lack of information and education and also the ubiquitous nature of allergens, accidental exposures to food allergens are not uncommon. The fear of potential fatal reactions and the need of a proper avoidance leads in most of the cases to the limitation of leisure and social activities. This review aims to be a practical approach on education and accidental exposure prevention regarding activities like shopping, eating out, and travelling. The recommendations are focused especially on proper reading of food labels and the management of the disease, namely in restaurants and airplanes, concerning cross-contact and communication with other stakeholders. The implementation of effective tools is essential to manage food allergy outside home, avoid serious allergic reactions and minimize the disease's impact on individuals' quality of life.

  12. Prevention of accidental exposure in radiotherapy: the risk matrix approach.

    PubMed

    Vilaragut, J J; Duménigo, C; Delgado, J M; Morales, J; McDonnell, J D; Ferro, R; Ortiz López, P; Ramírez, M L; Pérez Mulas, A; Papadopulos, S; Gonçalves, M; López Morones, R; Sánchez Cayuela, C; Cascajo Castresana, A; Somoano, F; Álvarez, C; Guillén, A; Rodríguez, M; Pereira, P P; Nader, A

    2013-02-01

    Knowledge and lessons from past accidental exposures in radiotherapy are very helpful in finding safety provisions to prevent recurrence. Disseminating lessons is necessary but not sufficient. There may be additional latent risks for other accidental exposures, which have not been reported or have not occurred, but are possible and may occur in the future if not identified, analyzed, and prevented by safety provisions. Proactive methods are available for anticipating and quantifying risk from potential event sequences. In this work, proactive methods, successfully used in industry, have been adapted and used in radiotherapy. Risk matrix is a tool that can be used in individual hospitals to classify event sequences in levels of risk. As with any anticipative method, the risk matrix involves a systematic search for potential risks; that is, any situation that can cause an accidental exposure. The method contributes new insights: The application of the risk matrix approach has identified that another group of less catastrophic but still severe single-patient events may have a higher probability, resulting in higher risk. The use of the risk matrix approach for safety assessment in individual hospitals would provide an opportunity for self-evaluation and managing the safety measures that are most suitable to the hospital's own conditions.

  13. Outcome of accidental peritoneal dialysis catheter holes or tip exposure.

    PubMed

    Silverstein, Douglas M; Wilcox, Jennifer E

    2010-06-01

    Pediatric peritoneal dialysis (PD) patients are at risk for acute peritonitis. One risk factor is accidental exposure of the catheter to a non-sterile surface. We studied catheter exposures in 17 pediatric patients receiving PD who developed 16 holes and 12 other accidental exposures. The rate of exposures was 3.7 events/100 patient-months. After exposure, the mean counts (+ or - standard error) of white blood cells (WBC), red blood cells, and neutrophils were 39.8 + or - 19.3, 9.5 + or - 7.1, and 24.2 + or - 5.3/mm(3), respectively. There was a trend towards higher peritoneal fluid WBC in patients with holes than in those with exposures (60.1 + or - 34.8 vs. 15.4 + or - 5.1/mm(3), respectively; p = 0.2). The initial peritoneal fluid WBC count was significantly higher if there was a positive culture than a negative culture (165.0 + or - 132.6 vs. 20.3 + or - 6.4/mm(3), respectively; p = 0.01). The percentage of neutrophils was higher in patients with a positive culture than in those with a negative culture (54.7 + or - 14.1 vs. 19.1 + or - 4.9%, respectively; p = 0.01). Of the 28 patients, 27 received a single dose of intravenous antibiotics, as per the protocol at that time. Among those treated, 7% developed a positive culture (all staphylococcal species) while 93% had a negative culture. We conclude that following accidental exposure of the peritoneal dialysis catheter: (1) the prevalence of peritonitis is low; (2) measuring peritoneal fluid WBC provides treatment guidance; (3) if treatment is initiated, it should be applied intraperitoneally and include activity against Gram-positive organisms.

  14. Accidental mydriasis from exposure to Angel's trumpet (Datura suaveolens).

    PubMed

    Havelius, Ulf; Asman, Peter

    2002-06-01

    To report clinical findings after accidental instillation into the eye of sap from Angel's trumpet (Datura suaveolens). We report findings on seven patients who developed sudden onset of unilateral mydriasis. At least three of them also had ipsilateral cycloplegia and one developed transient tachycardia. The symptoms evolved after ocular exposure to sap from Angel's trumpet, a plant containing natural alkaloids with parasympatholytic properties. Six patients were initially unaware of the cause of their symptoms. In these cases, patient history revealed recent contact with Angel's trumpet. Accidental ocular instillation of sap from Angel's trumpet should be noted as a cause of sudden onset of mydriasis in otherwise unaffected patients and also of general symptoms like tachycardia.

  15. Exhaled nitric oxide in children after accidental exposure to chlorine gas.

    PubMed

    Grasemann, Hartmut; Tschiedel, Eva; Groch, Manuela; Klepper, Jörg; Ratjen, Felix

    2007-08-01

    Chronic exposure to chlorine gas has been shown to cause occupational asthma. Acute inhalation of chlorine is known to cause airway inflammation and induce airway nitric oxide formation. Exhaled nitric oxide may therefore be a marker of airway damage after chlorine gas exposure. After accidental chlorine gas exposure in a swimming pool, exhaled nitric oxide and pulmonary function were repeatedly measured in 18 children over a 1-mo period. Symptomatic children with impaired pulmonary function had higher nitric oxide levels on the day after the exposure compared to day 8 and day 28. Differences in exhaled nitric oxide were more pronounced at a higher exhalation flow compared to lower flow, suggesting peripheral rather than central airway damage. This was in accordance with the observed changes in pulmonary function. No changes in exhaled nitric oxide were seen in asymptomatic children. These data suggest that acute chlorine gas exposure results in a mild increase of exhaled nitric oxide in symptomatic children.

  16. Phosgene exposure: a case of accidental industrial exposure.

    PubMed

    Hardison, Lewis S; Wright, Edward; Pizon, Anthony F

    2014-03-01

    Phosgene is a rare exposure with strong clinical implications. We report a phosgene exposure that resulted in the patient's death. A 58 year-old man arrived to the emergency department 1 hour after exposure to phosgene with complaints of a sore throat. Initial vital signs were blood pressure 175/118 mmHg, heart rate 98/min, respirations 12/min, and oxygen saturation of 93% on room air. Physical exam revealed few scattered rhonchi, without signs of distress. Initial arterial blood gases (ABG's) revealed pH 7.42, pCO2 43 mmHg, pO2 68 mmHg, HCO3 27 meq/L, and oxygen saturation of 93% on room air. Initial chest x-ray 2 hours after the exposure demonstrated clear lung fields. Approximately 2.5 hours after the exposure, he began complaining of dyspnea, restlessness and his oxygen saturation dropped below 90%. He received nebulized albuterol, 1 gram intravenous methylprednisolone, and 100 % oxygen via face mask. Minimal improvement was noted and he was intubated. The post intubation chest x-ray, 3.5 hours after the exposure, revealed diffuse alveolar infiltrates. Acetylcysteine, terbutaline, and IV steroids were administered without improvement. The patient died 30 hours after exposure. There are many misunderstandings concerning phosgene due to its rare presentation. Traditional treatment modalities are often unproven in human trials and were unsuccessful in this case. This case highlights the significant toxicity that results from phosgene exposure and the challenges of the limited treatment modalities. There is concern for the use of this agent in chemical terrorism.

  17. Dose assessment of an accidental exposure at the IPNS

    SciTech Connect

    Campos Torres, M.M.

    1995-02-01

    Seven different methods were used to estimate the dose rate to a female worker who was accidentally exposed in the neutron PHOENIX beamline at the IPNS. Theoretical and measured entrance dose ranged from 550 mrem/min to 2850 mrem/min. Theoretical estimates were based on a Monte Carlo simulation of a spectrum provided by IPNS (Crawford Spectrum). Dose measurements were made with TLDs on phantoms and with ionization chambers in a water phantom. Estimates of the whole body total effective dose equivalent (TEDE) rate ranged from 5.2 mrem/min to 840 mrem/min. Assumed and measured quality factors ranged from 2.6 to 11.8. Cytogenetic analyses of blood samples detected no positive exposure. The recommended TEDE rate was 158 mrem/min. The TEDE was 750 mrem.

  18. Dose assessment of an accidental exposure at IPNS

    SciTech Connect

    Torres, M.M.C.

    1996-05-01

    Seven different methods were used to estimate the dose rate to a female worker who was accidentally exposed in the neutron PHOENIX beamline at the IPNS. Theoretical and measured entrance dose rates ranged from 550 mrem/min to 2,850 mrem/min. Theoretical estimates were based on a Monte Carlo simulation of a spectrum provided by IPNS (Crawford Spectrum). Dose measurements were made with TLDs on phantoms and with ionization chambers in a water phantom. Estimates of the whole body total effective dose equivalent (TEDE) rate ranged from 5.2 mrem/min to 840 mrem/min. Assumed and measured quality factors ranged from 2.6 to 11.8. Cytogenic analyses of blood samples detected no positive exposure. The recommended TEDE rate was 158 mrem/min. The TEDE was 750 mrem.

  19. Acute health effects of accidental chlorine gas exposure

    PubMed Central

    2014-01-01

    Objectives This study was conducted to report the course of an accidental release of chlorine gas that occurred in a factory in Gumi-si, South Korea, on March 5, 2013. We describe the analysis results of 2 patients hospitalized because of chlorine-induced acute health problems, as well as the clinical features of 209 non-hospitalized patients. Methods We analyzed the medical records of the 2 hospitalized patients admitted to the hospital, as well as the medical records and self-report questionnaires of 209 non-hospitalized patients completed during outpatient treatment. Results Immediately after the exposure, the 2 hospitalized patients developed acute asthma-like symptoms such as cough and dyspnea, and showed restrictive and combined pattern ventilatory defects on the pulmonary function test. The case 1 showed asthma-like symptoms over six months and diurnal variability in peak expiratory flow rate was 56.7%. In case 2, his FEV1 after treatment (93%) increased by 25% compared to initial FEV1 (68%). Both cases were diagnosed as chlorine-induced reactive airways dysfunction syndrome (RADS) on the basis of these clinical features. The most frequent chief complaints of the 209 non-hospitalized patients were headache (22.7%), followed by eye irritation (18.2%), nausea (11.2%), and sore throat (10.8%), with asymptomatic patients accounting for 36.5%. The multiple-response analysis of individual symptom revealed headache (42.4%) to be the most frequent symptom, followed by eye irritation (30.5%), sore throat (30.0%), cough (29.6%), nausea (27.6%), and dizziness (27.3%). Conclusions The 2 patients hospitalized after exposure to chlorine gas at the leakage site showed a clinical course corresponding to RADS. All of the 209 non-hospitalized patients only complained of symptoms of the upper airways and mucous membrane irritation. PMID:25852940

  20. Persistent Seroconversion after Accidental Eye Exposure to Calcifying Nanoparticles

    NASA Technical Reports Server (NTRS)

    Ciftcioglu, Neva; Aho, Katja M.; McKay, David S.; Kajander, E. Olavi

    2007-01-01

    Biosafety of nanomaterials has attracted much attention recently. We report here a case where accidental human eye exposure to biogenic nanosized calcium phosphate in the form of calcifying nanoparticles (CNP) raised a strong IgG immune response against proteins carried by CNP. The antibody titer has persisted over ten years at the high level. The IgG was detected by ELISA using CNPs propagated in media containing bovine and human serum as antigen. The exposure incident occurred to a woman scientist (WS) at a research laboratory in Finland at 1993. CNP, also termed "nanobacteria", is a unique self-replicating agent that has not been fully characterized and no data on biohazards were available at that time. Before the accident, her serum samples were negative for both CNP antigen and anti-CNP antibody using specific ELISA tests (Nanobac Oy, Kuopio, Finland). The accident occurred while WS was harvesting CNP cultures. Due to a high pressure in pipetting, CNP pellet splashed into her right eye. Both eyes were immediately washed with water and saline. The following days there was irritation and redness in the right eye. These symptoms disappeared within two weeks without any treatment. Three months after the accident, blood and urine samples of WS were tested for CNP cultures (2), CNP-specific ELISA tests, and blood cell counts. Blood cell counts were normal, CNP antigen and culture tests were negative. A high IgG anti-CNP antibody titer was detected (see Figure). The antibodies of this person have been used thereafter as positive control and standard in ELISA manufacturing (Nano-Sero IgG ELISA, Nanobac Oy, Kuopio, Finland).

  1. Laboratory-Acquired Parasitic Infections from Accidental Exposures

    PubMed Central

    Herwaldt, Barbara L.

    2001-01-01

    Parasitic diseases are receiving increasing attention in developed countries in part because of their importance in travelers, immigrants, and immunocompromised persons. The main purpose of this review is to educate laboratorians, the primary readership, and health care workers, the secondary readership, about the potential hazards of handling specimens that contain viable parasites and about the diseases that can result. This is accomplished partly through discussion of the occupationally acquired cases of parasitic infections that have been reported, focusing for each case on the type of accident that resulted in infection, the length of the incubation period, the clinical manifestations that developed, and the means by which infection was detected. The article focuses on the cases of infection with the protozoa that cause leishmaniasis, malaria, toxoplasmosis, Chagas' disease (American trypanosomiasis), and African trypanosomiasis. Data about 164 such cases are discussed, as are data about cases caused by intestinal protozoa and by helminths. Of the 105 case-patients infected with blood and tissue protozoa who either recalled an accident or for whom the likely route of transmission could be presumed, 47 (44.8%) had percutaneous exposure via a contaminated needle or other sharp object. Some accidents were directly linked to poor laboratory practices (e.g., recapping a needle or working barehanded). To decrease the likelihood of accidental exposures, persons who could be exposed to pathogenic parasites must be thoroughly instructed in safety precautions before they begin to work and through ongoing training programs. Protocols should be provided for handling specimens that could contain viable organisms, using protective clothing and equipment, dealing with spills of infectious organisms, and responding to accidents. Special care should be exercised when using needles and other sharp objects. PMID:11585780

  2. Acute radiation syndrome caused by accidental radiation exposure - therapeutic principles.

    PubMed

    Dörr, Harald; Meineke, Viktor

    2011-11-25

    Fortunately radiation accidents are infrequent occurrences, but since they have the potential of large scale events like the nuclear accidents of Chernobyl and Fukushima, preparatory planning of the medical management of radiation accident victims is very important. Radiation accidents can result in different types of radiation exposure for which the diagnostic and therapeutic measures, as well as the outcomes, differ. The clinical course of acute radiation syndrome depends on the absorbed radiation dose and its distribution. Multi-organ-involvement and multi-organ-failure need be taken into account. The most vulnerable organ system to radiation exposure is the hematopoietic system. In addition to hematopoietic syndrome, radiation induced damage to the skin plays an important role in diagnostics and the treatment of radiation accident victims. The most important therapeutic principles with special reference to hematopoietic syndrome and cutaneous radiation syndrome are reviewed.

  3. Accidental phosgene gas exposure: A review with background study of 10 cases.

    PubMed

    Vaish, Arvind Kumar; Consul, Shuchi; Agrawal, Avinash; Chaudhary, Shyam Chand; Gutch, Manish; Jain, Nirdesh; Singh, Mohit Mohan

    2013-10-01

    Here, authors present a review on clinical presentation and management of exposure of phosgene gas after reviewing the literature by searching with keywords phosgene exposure on Google, Cochrane, Embase and PubMed with a background of experience gained from 10 patients who were admitted to our institute after an accidental phosgene exposure in February 2011 nearby a city in India. Phosgene is a highly toxic gas, occupational workers may have accidental exposure. The gas can also be generated inadvertently during fire involving plastics and other chemicals and solvents containing chlorine, which is of concern to emergency responders. Phosgene inhalation may cause initially symptoms of respiratory tract irritation, patients feel fine thereafter, and then die of choking a day later because of build up of fluid in the lungs (delayed onset non-cardiogenic pulmonary edema). Phosgene exposure is associated with significant morbidity and mortality. Patients with a history of exposure should be admitted to the hospital for a minimum of 24 h for observation because of the potential for delayed onset respiratory failure and acute respiratory distress syndrome.

  4. Accidental phosgene gas exposure: A review with background study of 10 cases

    PubMed Central

    Vaish, Arvind Kumar; Consul, Shuchi; Agrawal, Avinash; Chaudhary, Shyam Chand; Gutch, Manish; Jain, Nirdesh; Singh, Mohit Mohan

    2013-01-01

    Here, authors present a review on clinical presentation and management of exposure of phosgene gas after reviewing the literature by searching with keywords phosgene exposure on Google, Cochrane, Embase and PubMed with a background of experience gained from 10 patients who were admitted to our institute after an accidental phosgene exposure in February 2011 nearby a city in India. Phosgene is a highly toxic gas, occupational workers may have accidental exposure. The gas can also be generated inadvertently during fire involving plastics and other chemicals and solvents containing chlorine, which is of concern to emergency responders. Phosgene inhalation may cause initially symptoms of respiratory tract irritation, patients feel fine thereafter, and then die of choking a day later because of build up of fluid in the lungs (delayed onset non-cardiogenic pulmonary edema). Phosgene exposure is associated with significant morbidity and mortality. Patients with a history of exposure should be admitted to the hospital for a minimum of 24 h for observation because of the potential for delayed onset respiratory failure and acute respiratory distress syndrome. PMID:24339660

  5. Orofacial manifestations from accidental exposure to caesium 137 in Goiania, Brazil.

    PubMed

    Gomes, M A; Wascheck, C de C; Scully, C; Almeida, O de P; Bozzo, L

    1990-08-01

    The accidental close exposure of over 200 adults and children to a caesium-137 (137Cs) source in Goiania, Brazil in 1987 produced significant short-term morbidity in about 50 patients, and four deaths within a few weeks. Some 57% of those maximally exposed to radiation, developed orofacial lesions, notably purpura, spontaneous bleeding, ulcers and/or acute candidiasis. These lesions were probably mainly the consequences of depression of bone marrow elements by the radionuclide. Though the oral lesions that may follow iatrogenic exposure to ionizing radiation are well recognized this appears to be the first report on the oral sequelae of a serious radiation accident.

  6. Triage and Management of Accidental Laboratory Exposures to Biosafety Level-3 and -4 Agents

    PubMed Central

    Rodak, Colleen; Bray, Mike; Davey, Richard T.

    2009-01-01

    The recent expansion of biocontainment laboratory capacity in the United States has drawn attention to the possibility of occupational exposures to BSL-3 and -4 agents and has prompted a reassessment of medical management procedures and facilities to deal with these contingencies. A workshop hosted by the National Interagency Biodefense Campus was held in October 2007 and was attended by representatives of all existing and planned BSL-4 research facilities in the U.S. and Canada. This report summarizes important points of discussion and recommendations for future coordinated action, including guidelines for the engineering and operational controls appropriate for a hospital care and isolation unit. Recommendations pertained to initial management of exposures (ie, immediate treatment of penetrating injuries, reporting of exposures, initial evaluation, and triage). Isolation and medical care in a referral hospital (including minimum standards for isolation units), staff recruitment and training, and community outreach also were addressed. Workshop participants agreed that any unit designated for the isolation and treatment of laboratory employees accidentally infected with a BSL-3 or -4 pathogen should be designed to maximize the efficacy of patient care while minimizing the risk of transmission of infection. Further, participants concurred that there is no medically based rationale for building care and isolation units to standards approximating a BSL-4 laboratory. Instead, laboratory workers accidentally exposed to pathogens should be cared for in hospital isolation suites staffed by highly trained professionals following strict infection control procedures. PMID:19634998

  7. Management of accidental exposure to HIV: the COREVIH 2011 activity report.

    PubMed

    Rouveix, E; Bouvet, E; Vernat, F; Chansombat, M; Hamet, G; Pellissier, G

    2014-03-01

    Post-exposure prophylaxis (PEP) relies on procedures allowing quick access to treatment in case of accidental exposure to viral risk (AEV). Occupational blood exposure (OBE) affects mainly caregivers; these accidents are monitored and assessed by the inter-regional center for nosocomial infections (C-CLIN), occupational physicians, and infection control units. They are classified apart from sexual exposure for which there is currently no monitoring. Data was extracted from the COREVIH (steering committee for the prevention of HIV infection) 2011 activity reports (AR), available online. Data collection was performed using a standardized grid. Twenty-four out of 28 AR were available online. Nine thousand nine hundred and twenty AEV were reported, 44% of OBE, and 56% of sexual and other exposures. PEP was prescribed in 8% of OBE and in 77% of sexual exposures. The type of PEP was documented in 52% of the cases. Follow-up was poorly documented. AR provide an incomplete and heterogeneous review of exposure management without any standardized data collection. The difficulties encountered in data collection and monitoring are due to differences in care centers (complex patient circuits, multiple actors) and lack of common dedicated software. Sexual exposures account for 50% of AEV and most are treated; but they are incompletely reported and consequently not analyzed at the regional or national level. A typical AR collection grid is being studied in 2 COREVIH, with the objective to improve collection and obtain useful national data. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Quantification of nerve agent VX-butyrylcholinesterase adduct biomarker from an accidental exposure.

    PubMed

    Solano, Maria I; Thomas, Jerry D; Taylor, James T; McGuire, Jeffrey M; Jakubowski, Edward M; Thomson, Sandra A; Maggio, Vincent L; Holland, Kerry E; Smith, J Richard; Capacio, Benedict; Woolfitt, Adrian R; Ashley, David L; Barr, John R

    2008-01-01

    The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80 nM, it can be calculated that inhibition levels of >or= 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.

  9. Is your office prepared for an accidental needlestick or other unexpected exposure incident?

    PubMed

    Alexander, Roger E; Limes, Sharon

    2010-01-01

    Recommendations and mandatory guidelines for preventing and managing needlestick incidents and other accidental exposures to bloodborne pathogens in healthcare facilities have been published by the Occupational Safety and Health Administration (OSHA) and the Centers for Disease Control and Prevention (CDC) for more than 2 decades. Over the years, the incidence of official enforcement actions has declined and a complacency about the standards may have evolved in some dental offices. Some practitioners may not have written an occupational exposure incident protocol or made appropriate arrangements for medical laboratory testing and postexposure medical evaluation following an unexpected needlestick or other exposure incident in the office. When an unexpected event occurs, practitioners may become confused regarding the steps to be taken, and may turn to their local dental society or fellow practitioners for guidance. The provided information may or may not be complete, accurate and/or current. Implementation of periodic personnel training to prevent exposure incidents is extremely important and could ultimately save a dental practice thousands of dollars in expenses related to the occurrence of even one exposure incident, as well as save the life and/or career of a dental healthcare provider. This article does not comprehensively detail all infection control and bloodborne pathogen transmission prevention requirements for dental offices. Rather, the article provides suggestions for dental practitioners regarding the step by step management of exposure incidents, and provides resource information for additional steps that can be taken towards prevention, improved office compliance, and improved litigation protection.

  10. Elimination kinetics of metals after an accidental exposure to welding fumes.

    PubMed

    Schaller, Karl H; Csanady, György; Filser, Johannes; Jüngert, Barbara; Drexler, Hans

    2007-07-01

    We had the opportunity to study the kinetics of metals in blood and urine samples of a flame-sprayer exposed to high accident-prone workplace exposure. We measured over 1 year, the nickel, aluminium, and chromium concentrations in blood and urine specimens after exposure. On this basis, we evaluated the corresponding half-lives. Blood and urine sampling were carried out five times after accidental exposure over a period of 1 year. The metals were analysed by graphite furnace atomic absorption spectrometry and Zeeman compensation with reliable methods. Either a mono-exponential or a bi-exponential function was fitted to the concentration-time courses of selected metals using weighted least squares non-linear regression analysis. The amount excreted in urine was calculated integrating the urinary decay curve and multiplying with the daily creatinine excretion. The first examination was carried out 15 days after exposure. The mean aluminium concentration in plasma was 8.2 microg/l and in urine, 58.4 microg/g creatinine. The mean nickel concentration in blood was 59.6 microg/l and the excretion in urine 700 microg/g creatinine. The mean chromium level in blood was 1.4 microg/l in urine, 7.4 microg/g creatinine. For the three elements, the metal concentrations in blood and urine exceeded the reference values at least in the initial phase. For nickel, the German biological threshold limit values (EKA) were exceeded. Aluminium showed a mono-exponential decay, whereas the elimination of chromium and nickel was biphasic in biological fluids of the accidentally exposed welder. The half-lives were as follows: for aluminium 140 days (urine) and 160 days (plasma); for chromium 40 and 730 days (urine); for nickel 25 and 610 days (urine) as well as 30 and 240 days (blood). The renal clearance of aluminium and nickel was about 2 l/h estimated for the last monitoring day.

  11. Accidental exposure to UV radiation produced by germicidal lamp: case report and risk assessment.

    PubMed

    Zaffina, Salvatore; Camisa, Vincenzo; Lembo, Marco; Vinci, Maria Rosaria; Tucci, Mario Graziano; Borra, Massimo; Napolitano, Antonio; Cannatà, Vittorio

    2012-01-01

    Ultraviolet radiation is known to cause both benefits and harmful effects on humans. The adverse effects mainly involve two target organs, skin and eye, and can be further divided into short- and long-term effects. The present case report describes an accidental exposure of two health-care workers to ultraviolet radiation produced by a germicidal lamp in a hospital pharmacy. The germicidal lamp presented a spectrum with an intense UV-C component as well as a modest UV-B contribution. Overexposure to UV-C radiation was over 100 times as large as the ICNIRP exposure limits. A few hours after the exposure, the two subjects reported symptoms of acute UV injury and both of them continued having significant clinical signs for over 2 years. In this study, we describe acute and potentially irreversible effects caused by high UV exposure. In addition, we present the results of risk assessment by occupational exposure to germicidal lamps. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  12. Acute health effects after accidental exposure to styrene from drinking water in Spain

    PubMed Central

    Arnedo-Pena, Alberto; Bellido-Blasco, Juan; Villamarin-Vazquez, Jose-Luis; Aranda-Mares, Jose-Luis; Font-Cardona, Nuria; Gobba, Fabriziomaria; Kogevinas, Manolis

    2003-01-01

    Objectives We studied subjective health symptoms in a population accidentally exposed to high styrene concentrations in drinking tap water. The contamination occurred during the reparation of a water tank. Methods Residents of 27 apartments in two buildings using the contaminated water were contacted. A questionnaire on subjective symptoms was administered to 84 out of 93 persons living in the apartments at the time of the accident. Styrene concentration was measured in samples of water collected two days after the accident. The means of exposure associated with appearance of symptoms were examined through case-control analyses. Results Styrene in water reached concentrations up to 900 μg/L. Symptoms were reported by 46 persons (attack rate 55 %). The most frequent symptoms were irritation of the throat (26%), nose (19%), eyes (18%) and the skin (14%). General gastrointestinal symptoms were observed with 11% reporting abdominal pain and 7% diarrhea. The factors most strongly associated with symptoms were drinking tap water (OR = 7.8, 95% CI 1.3–48), exposure to vapors from the basement (OR = 10.4, 2.3–47) and eating foods prepared with tap water (OR = 8.6, 1.9–40). All residents in the ground floor reported symptoms. Conclusions This accidental contamination led to very high styrene concentrations in water and was related to a high prevalence of subjective symptoms of the eyes, respiratory tract and skin. Similar exposures have been described in workers but not in subjects exposed at their residence. Various gastrointestinal symptoms were also observed in this population probably due to a local irritative effect. PMID:12777181

  13. Accidental occupational exposure of intravenous nurses to human immunodeficiency virus. Anticipating the consequences.

    PubMed

    Meisenhelder, J B

    1998-01-01

    This descriptive study randomly surveyed all 302 Massachusetts members of the Intravenous Nurses Society in 1991 regarding their perceptions of nine possible consequences of human immunodeficiency virus (HIV) infection caused by accidental occupational exposure. Areas of highest concern were financial: adequacy of worker's compensation, ability of the employer to cover all healthcare costs, and job security. Nurses also were concerned about confidentiality of their HIV status and personal history jeopardizing their benefits. The i.v. nurses felt most secure in areas of their personal lives: housing and support of family and friends. Although some concerns correlated significantly with fear of contagion, others were unrelated, indicating a need for policy and attitude changes to promote comfort in working with HIV.

  14. Accidental exposures to blood and body fluids among health care workers in dental teaching clinics: a prospective study.

    PubMed

    Ramos-Gomez, F; Ellison, J; Greenspan, D; Bird, W; Lowe, S; Gerberding, J L

    1997-09-01

    The authors evaluated accidental exposures to blood and body fluids reported to a hotline or to health officials at four dental teaching clinics. The authors used a standard questionnaire to solicit and record data regarding each exposure. During a 63-month period, 428 parenteral exposures to blood or body fluids were documented. Dental students and dental assistants had the highest rates of exposure. Syringe needle injuries were the most common type of exposure, while giving injections, cleaning instruments after procedures and drilling were the activities most frequently associated with exposures.

  15. Acute accidental exposure to chlorine gas: clinical presentation, pulmonary functions and outcomes.

    PubMed

    Mohan, Alladi; Kumar, S Naveen; Rao, M H; Bollineni, S; Manohar, I Chiranjeevi

    2010-01-01

    To study the clinical presentation, pulmonary functions and outcomes in subjects who were accidentally exposed to chlorine gas. Prospective observational study of 64 patients who sustained acute accidental exposure to chlorine gas during a leak in the chlorination system of the public bathing pool of a temple. The major presenting symptoms and signs included acute dyspnoea (100%), chest discomfort (100%), cough (97%), eye irritation (88%), giddiness (72%), vomiting (46%), and heaviness in the head (44%); tachycardia (100%), tachypnoea (96%) and polyphonic wheezing (28%). All patients were managed in the emergency room with humidified oxygen inhalation and beta-2 agonist nebulisation and 52 were discharged within six hours. Twelve patients were severely affected and required hospitalisation; three of them were admitted into the intensive care unit. Three patients developed pulmonary oedema six to eight hours following admission. Pulmonary function testing (n = 12) at presentation revealed obstructive defect in eight and mixed obstructive-cum-restrictive defect in four patients. The mean duration of hospital stay was 5.1 +/- 2.1 days. None of the patients died. Reactive airway dysfunction syndrome (RADS) was observed in three of the 12 hospitalised patients, who complained of manifested persistent cough that lasted for three months period following discharge. Serial pulmonary functions recovered to normal range by the end of the six months in all patients and remained so at one-year follow-up. Acute exposure to chlorine gas is an uncommon, but important public health hazard and can cause RADS, acute lung injury and pulmonary function abnormalities, which are reversible on prompt and appropriate management.

  16. Accidental bilateral Q-switched neodymium laser exposure: treatment and recovery of visual function

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Stuck, Bruce E.; Dunlap, Weldon; Scales, David K.; Lund, David J.; Ness, James W.

    1998-05-01

    A 21 year old female was accidentally exposed in both eyes when she looked into the 10 cm exit aperture of a military laser designator emitting 1064 nm q-switched (30 ns) pulses at a 10 pulse per second rate. Steroid therapy (methylprednisolone sodium succinate) was initiated within 6 hours post exposure. Initial ophthalmoscopic observation revealed small contained macular hemorrhages in each eye. Fluorescein angiography (FA) showed minimal leakage. Visual acuity was 20/100 and 20/60 in OD and OS respectively. Contrast sensitivity in both eyes was depressed across all spatial frequencies by more than 1.5 log units. At four weeks post exposure, no significant macular scarring was apparent and visual acuity returned to 20/25 in both eyes. Contrast sensitivity had improved to normal levels with a peak at 3 cycles/degree. At one year post exposure, visual acuity was 20/13 in both eyes and measures of contrast sensitivity were within normal limits. During the course of recovery, the patient's fixation shifted from a slightly superior temporal site back to the central foveal region. The foveal lesion sites were still evident by ophthalmoscopy and Amsler grid measurements but were deemed functional when the patient placed small targets generated by the scanning laser ophthalmoscope in the lesion site for discrimination. This outcome indicates remarkable recovery of visual function and suggests that early administration of steroids may assist in preserving the natural neural recovery process of the photoreceptor matrix by minimizing intraretinal scar formation.

  17. Medical documentation, bioanalytical evidence of an accidental human exposure to sulfur mustard and general therapy recommendations.

    PubMed

    Steinritz, Dirk; Striepling, Enno; Rudolf, Klaus-Dieter; Schröder-Kraft, Claudia; Püschel, Klaus; Hullard-Pulstinger, Andreas; Koller, Marianne; Thiermann, Horst; Gandor, Felix; Gawlik, Michael; John, Harald

    2016-02-26

    Sulfur mustard (SM) is a chemical warfare agent (CWA) that was first used in World War I and in several military conflicts afterwards. The threat by SM is still present even today due to remaining stockpiles, old and abandoned remainders all over the world as well as to its ease of synthesis. CWA are banned by the Chemical Weapons Convention (CWC) interdicting their development, production, transport, stockpiling and use and are subjected to controlled destruction. The present case report describes an accidental exposure of three workers that occurred during the destruction of SM. All exposed workers presented a characteristic SM-related clinical picture that started about 4h after exposure with erythema and feeling of tension of the skin at the upper part of the body. Later on, superficial blister and a burning phenomenon of the affected skin areas developed. Similar symptoms occurred in all three patients differing severity. One patient presented sustained skin affections at the gluteal region while another patient came up with affections of the axilla and genital region. Fortunately, full recovery was observed on day 56 after exposure except some little pigmentation changes that were evident even on day 154 in two of the patients. SM-exposure was verified for all three patients using bioanalytical GC MS and LC MS/MS based methods applied to urine and plasma. Urinary biotransformation products of the β-lyase pathway were detected until 5 days after poisoning whereas albumin-SM adducts could be found until day 29 underlining the beneficial role of adduct detection for post-exposure verification. In addition, we provide general recommendations for management and therapy in case of SM poisoning.

  18. Accidental Falls and Risk of Mortality among Older Adults on Chronic Peritoneal Dialysis

    PubMed Central

    Farragher, Janine; Chiu, Ernest; Ulutas, Ozkan; Tomlinson, George; Cook, Wendy L.

    2014-01-01

    Background and objectives More than 40% of elderly hemodialysis patients experience one or more accidental falls within a 1-year period. Such falls are associated with higher mortality. The objectives of this study were to assess whether falls are also common in elderly patients established on peritoneal dialysis and evaluate if patients with falls have a higher risk of mortality than patients who do not experience a fall. Design, setting, participants, & measurements Using a prospective cohort study design, patients ages≥65 years on chronic peritoneal dialysis from April 2002 to April 2003 at the University Health Network were recruited. Patients were followed biweekly, and falls occurring within the first 15 months were recorded. Outcome data were collected until death, study end (July 31, 2012), transplantation, or transfer to another dialysis center. Results Seventy-four of seventy-six potential patients were recruited, assessed at baseline, and followed biweekly for falls; 40 of 74 (54%) peritoneal dialysis patients experienced 89 falls (adjusted mean fall rate, 1.7 falls per patient-year; 95% confidence interval, 1.0 to 2.7). Patients with falls were more likely to have had previous falls, be more recently initiated onto dialysis, be men, be older, and have higher comorbidity. Twenty-eight patients died during the follow-up period. After adjustment for known risk factors, each successive fall was associated with a 1.62-fold higher mortality (hazard ratio, 1.62; 95% confidence interval, 1.29 to 2.02; P<0.001). Conclusions Accidental falls are common in the peritoneal dialysis population and often go unrecognized. Falls were associated with higher mortality risk. Because fall interventions are effective in other populations, screening peritoneal dialysis patients for falls may be a simple measure of clinical importance. PMID:24763867

  19. Accidental falls and risk of mortality among older adults on chronic peritoneal dialysis.

    PubMed

    Farragher, Janine; Chiu, Ernest; Ulutas, Ozkan; Tomlinson, George; Cook, Wendy L; Jassal, Sarbjit V

    2014-07-01

    More than 40% of elderly hemodialysis patients experience one or more accidental falls within a 1-year period. Such falls are associated with higher mortality. The objectives of this study were to assess whether falls are also common in elderly patients established on peritoneal dialysis and evaluate if patients with falls have a higher risk of mortality than patients who do not experience a fall. Using a prospective cohort study design, patients ages ≥ 65 years on chronic peritoneal dialysis from April 2002 to April 2003 at the University Health Network were recruited. Patients were followed biweekly, and falls occurring within the first 15 months were recorded. Outcome data were collected until death, study end (July 31, 2012), transplantation, or transfer to another dialysis center. Seventy-four of seventy-six potential patients were recruited, assessed at baseline, and followed biweekly for falls; 40 of 74 (54%) peritoneal dialysis patients experienced 89 falls (adjusted mean fall rate, 1.7 falls per patient-year; 95% confidence interval, 1.0 to 2.7). Patients with falls were more likely to have had previous falls, be more recently initiated onto dialysis, be men, be older, and have higher comorbidity. Twenty-eight patients died during the follow-up period. After adjustment for known risk factors, each successive fall was associated with a 1.62-fold higher mortality (hazard ratio, 1.62; 95% confidence interval, 1.29 to 2.02; P<0.001). Accidental falls are common in the peritoneal dialysis population and often go unrecognized. Falls were associated with higher mortality risk. Because fall interventions are effective in other populations, screening peritoneal dialysis patients for falls may be a simple measure of clinical importance. Copyright © 2014 by the American Society of Nephrology.

  20. Modeling of occupational exposure to accidentally released manufactured nanomaterials in a production facility and calculation of internal doses by inhalation

    PubMed Central

    Vaquero-Moralejo, Celina; Jaén, María; Lopez De Ipiña Peña, Jesús; Neofytou, Panagiotis

    2016-01-01

    Background Occupational exposure to manufactured nanomaterials (MNMs) and its potential health impacts are of scientific and practical interest, as previous epidemiological studies associate exposure to nanoparticles with health effects, including increased morbidity of the respiratory and the circulatory system. Objectives To estimate the occupational exposure and effective internal doses in a real production facility of TiO2 MNMs during hypothetical scenarios of accidental release. Methods Commercial software for geometry and mesh generation, as well as fluid flow and particle dispersion calculation, were used to estimate occupational exposure to MNMs. The results were introduced to in-house software to calculate internal doses in the human respiratory tract by inhalation. Results Depending on the accidental scenario, different areas of the production facility were affected by the released MNMs, with a higher dose exposure among individuals closer to the particles source. Conclusions Granted that the study of the accidental release of particles can only be performed by chance, this numerical approach provides valuable information regarding occupational exposure and contributes to better protection of personnel. The methodology can be used to identify occupational settings where the exposure to MNMs would be high during accidents, providing insight to health and safety officials. PMID:27670588

  1. Assessment of long-term health risks after accidental exposure using haemoglobin adducts of epichlorohydrin.

    PubMed

    Wollin, Klaus-Michael; Bader, Michael; Müller, Michael; Lilienblum, Werner; Csicsaky, Michael

    2014-12-15

    On September 9th, 2002, two goods trains collided in Bad Münder, Lower Saxony, causing the release of more than 40 metric tonnes of epichlorohydrin (1-chloro-2,3-epoxypropane) into the environment. A human biomonitoring study was performed to evaluate the accidental exposure to epichlorohydrin and to assess the possible long-term, i.e. carcinogenic health effects. This was done on the basis of a biochemical effect monitoring using the N-(3-chloro-2-hydroxypropyl)valine and the N-(2,3-dihydroxypropyl)valine haemoglobin adducts of epichlorohydrin in blood to respond to missing ambient monitoring immediately after the crash. N-(3-chloro-2-hydroxypropyl)valine adduct levels above the LOQ (25 pmol/g globin) ranged from 32.0 to 116.4 pmol/g globin in 6 out of 628 samples. The N-(2,3-dihydroxypropyl)valine adduct was not detected above the LOD (10 pmol/g globin) in any of the blood samples. Based on the quantified N-(3-chloro-2-hydroxypropyl)valine adduct values, the body doses after two days of exposure were estimated to be in the range of 1.7-6.2 nmol/kg body weight. The reverse estimation of the external exposure leads to cumulative additional lifetime cancer risks ranging from 2.61×10(-8) to 9.48×10(-8). The estimated excess lifetime cancer risks have to be assessed as extremely low. Our biomonitoring study facilitated the dialogue between individuals and groups concerned and authorities, because suspected or occurred exposures and risks to human health could be quantified and interpreted in a sound manner.

  2. Unintended and accidental medical radiation exposures in radiology: guidelines on investigation and prevention.

    PubMed

    Martin, Colin J; Vassileva, J; Vano, Eliseo; Mahesh, M; Ebdon-Jackson, Steve; Ng, K; Frush, Donald P; Loose, R; Damilakis, John

    2017-08-24

    This paper sets out guidelines for managing radiation exposure incidents involving patients in diagnostic and interventional radiology. The work is based on collation of experiences from representatives of international and national organizations for radiologists, medical physicists, radiographers, regulators, and equipment manufacturers, derived from an International Atomic Energy Agency Technical Meeting. More serious overexposures can result in skin doses high enough to produce tissue reactions, in interventional procedures and computed tomography, most notably from perfusion studies. A major factor involved has been deficiencies in training of staff in operation of equipment and optimization techniques. The use of checklists and time outs before procedures commence, and dose alerts when critical levels are reached during procedures can provide safeguards to reduce risks of these effects occurring. However, unintended and accidental overexposures resulting in relatively small additional doses can take place in any diagnostic or interventional X-ray procedure and it is important to learn from errors that occur, as these may lead to increased risks of stochastic effects. Such events may involve the wrong examinations, procedural errors, or equipment faults. Guidance is given on prevention, investigation and dose calculation for radiology exposure incidents within healthcare facilities. Responsibilities should be clearly set out in formal policies, and procedures should be in place to ensure that root causes are identified and deficiencies addressed. When an overexposure of a patient or an unintended exposure of a foetus occurs, the foetal, organ, skin and/or effective dose may be estimated from exposure data. When doses are very low, generic values for the examination may be sufficient, but a full assessment of doses to all exposed organs and tissues may sometimes be required. The use of general terminology to describe risks from stochastic effects is recommended

  3. Risks from accidental exposures to engineered nanoparticles and neurological health effects: A critical review

    PubMed Central

    2010-01-01

    There are certain concerns regarding the safety for the environment and human health from the use of engineered nanoparticles (ENPs) which leads to unintended exposures, as opposed to the use of ENPs for medical purposes. This review focuses on the unintended human exposure of ENPs. In particular, possible effects in the brain are discussed and an attempt to assess risks is performed. Animal experiments have shown that investigated ENPs (metallic nanoparticles, quantum dots, carbon nanotubes) can translocate to the brain from different entry points (skin, blood, respiratory pathways). After inhalation or instillation into parts of the respiratory tract a very small fraction of the inhaled or instilled ENPs reaches the blood and subsequently secondary organs, including the CNS, at a low translocation rate. Experimental in vivo and in vitro studies have shown that several types of ENPs can have various biological effects in the nervous system. Some of these effects could also imply that ENPs can cause hazards, both acutely and in the long term. The relevance of these data for risk assessment is far from clear. There are at present very few data on exposure of the general public to either acute high dose exposure or on chronic exposure to low levels of air-borne ENPs. It is furthermore unlikely that acute high dose exposures would occur. The risk from such exposures for damaging CNS effects is thus probably very low, irrespective of any biological hazard associated with ENPs. The situation is more complicated regarding chronic exposures, at low doses. The long term accumulation of ENPs can not be excluded. However, we do not have exposure data for the general public regarding ENPs. Although translocation to the brain via respiratory organs and the circulation appears to be very low, there remains a possibility that chronic exposures, and/or biopersistent ENPs, can influence processes within the brain that are triggering or aggravating pathological processes. In

  4. Human color vision deficits induced by accidental laser exposure and potential for long-term recovery

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Lund, Brian J.; Brown, Jeremiah, Jr.; Stuck, Bruce E.; Loveday, J.

    2003-06-01

    Purpose: To evaluate long term deficits in human color discrimination induced by accidental laser macular damage and assess potential for recovery of color vision deficits. Methods: Nine laser accident cases (Q-switched Neodymium) presenting initially with confined or vitreous macular hemorrhage were evaluated with the Farnsworth-Munsell 100 Hue test within 2 days to 3 months post exposure. Both total as well as partial errors in the blue/yellow (B/Y) and red/green (R/G) regions were assessed. Independent assessment of axis orientation and complexity were obtained via a Fourier series expansion of error scores. Comparisons of both total and partial B/Y and R/G errors were made with age matched normal subjects, idiopathic and juvenile onset macular holes. Confocal Scanning Laser Ophthalmoscopy and Optical Coherence Tomography characterized the presence of retinal traction, intraretinal scar, macular thickness and macular hole formation. Results: Comparison of exposed and non-exposed age matched individuals were significant (P<.001) for both total and partial errors. In four cases where macular injury ranged from mild scar to macular hole, color discrimination errors achieved normal levels in 1 to 12 months post exposure. A mild tritan axis, dominant B/Y ("blue/yellow") errors, and retinal traction were observed in a macular hole case. At 12 months post exposure, traction about the hole disappeared, and total and partial errors were normal. Where damage involved a greater degree of scarring, retinal traction and multiple injury sites, long term recovery of total and partial error recovery was retarded with complex axis makeup. Single exposures in the paramacula produced tritan axes, while multiple exposures within and external to the macula increased total and partial R/G ("red/green") error scores. Total errors increased when paramacular hole enlargement induced macular traction. Such hole formation produced significant increases in total errors, complex axis

  5. Accidental ammonia exposure to county fair show livestock due to contaminated drinking water.

    PubMed

    Campagnolo, Enzo R; Kasten, Steve; Banerjee, Monty

    2002-10-01

    Nitrogen based fertilizers represent an important element in the farm economy, but their storage and use are associated with major risks to livestock and humans. An accidental ammonia exposure occurred at a Midwest county fair in Illinois. Six deaths occurred in show livestock; a Holstein cow, 3 Holstein heifers, a goat, and a lamb. Mortality was associated with consumption of water inadvertently contaminated with a liquid fertilizer containing ammonium nitrate and urea commonly used for irrigating agricultural crop fields and brought onto the fairgrounds by a tanker truck previously used to transport liquid fertilizer. The show animals that drank the contaminated water immediately became ill, developed seizures and died within a few hours. Postmortem findings were unremarkable to nonspecific. Rumen contents from the lamb, Holstein cow, and Holstein heifer had ammonia-nitrogen concentrations of l,000, 1,150 and 1,440 ppm, respectively. Water from the heifer's water bucket, the cow's water bucket, and the tanker truck, had nitrate levels of 6,336, 6,116, and 6,248 ppm, respectively. The ammonia toxicosis was attributed to the contaminated water brought onto the fairgrounds by the tankertruck that previously transported liquid ammonium nitrateand urea. This accident underscores the importance of meticulous observation of safety guidelines and measured working practices in agriculture and animal husbandry.

  6. Evaluation of health effects in Sequoyah Fuels Corporation workers from accidental exposure to uranium hexafluoride

    SciTech Connect

    Fisher, D.R. ); Swint, M.J.; Kathren, R.L. )

    1990-05-01

    Urine bioassay measurements for uranium and medical laboratory results were studied to determine whether there were any health effects from uranium intake among a group of 31 workers exposed to uranium hexafluoride (UF{sub 6}) and hydrolysis products following the accidental rupture of a 14-ton shipping cylinder in early 1986 at the Sequoyah Fuels Corporation uranium conversion facility in Gore, Oklahoma. Physiological indicators studied to detect kidney tissue damage included tests for urinary protein, casts and cells, blood, specific gravity, and urine pH, blood urea nitrogen, and blood creatinine. We concluded after reviewing two years of follow-up medical data that none of the 31 workers sustained any observable health effects from exposure to uranium. The early excretion of uranium in urine showed more rapid systemic uptake of uranium from the lung than is assumed using the International Commission on Radiological Protection (ICRP) Publication 30 and Publication 54 models. The urinary excretion data from these workers were used to develop an improved systemic recycling model for inhaled soluble uranium. We estimated initial intakes, clearance rates, kidney burdens, and resulting radiation doses to lungs, kidneys, and bone surfaces. 38 refs., 10 figs., 7 tabs.

  7. Effectiveness of common shelter-in-place techniques in reducing ammonia exposure following accidental release.

    PubMed

    Tarkington, Brett; Harris, Angela J; Barton, Paul S; Chandler, Ben; Goad, Phillip T

    2009-04-01

    Shelter-in-place strategies such as remaining indoors; breathing through a damp cloth; sealing cracks in windows and doors using towels, duct tape, or plastic sheeting; and running a shower are often recommended by emergency response officials to protect against accidental or intentional release of hazardous airborne chemicals and biologicals. Similar recommendations have been made to and used by community members exposed to anhydrous ammonia after catastrophic release of ammonia gas due to a derailment or other accidents. Such incidents have resulted in fatalities and serious injury to exposed individuals; however, other individuals within the same area have escaped injury and, in many cases, sustained no injuries as a result of sheltering-in-place. Although there are some studies that have evaluated the effectiveness of remaining in the home or breathing through a damp cloth to reduce exposure to various agents, there have been no studies that directly address the efficacy of running the shower in reducing exposure to ammonia gas. The present study was designed to simulate sheltering-in-place inside a typical bathroom with the shower running. The effectiveness of breathing through a damp cloth was also evaluated using a CPR mannequin placed inside a chamber built to represent a typical household bathroom. Ammonia gas at 300 or 1000 ppm was added to the chamber until the concentration peaked and stabilized, then the shower was turned on and the ammonia gas concentration was continuously monitored. In the mannequin studies, using a damp cloth reduced exposure to ammonia gas by 2- to 18-fold. Turning on the shower was even more effective at reducing ammonia levels. After 27 min, the ammonia concentration in the chamber was reduced to 2% of the initial concentration, even though gas was being continuously added to the chamber. These results indicate that use of shelter-in-place strategies substantially reduces ammonia exposure and that by combining shelter

  8. Management of accidental laboratory exposure to Burkholderia pseudomallei and B. mallei.

    PubMed

    Peacock, Sharon J; Schweizer, Herbert P; Dance, David A B; Smith, Theresa L; Gee, Jay E; Wuthiekanun, Vanaporn; DeShazer, David; Steinmetz, Ivo; Tan, Patrick; Currie, Bart J

    2008-07-01

    The gram-negative bacillus Burkholderia pseudomallei is a saprophyte and the cause of melioidosis. Natural infection is most commonly reported in northeast Thailand and northern Australia but also occurs in other parts of Asia, South America, and the Caribbean. Melioidosis develops after bacterial inoculation or inhalation, often in relation to occupational exposure in areas where the disease is endemic. Clinical infection has a peak incidence between the fourth and fifth decades; with diabetes mellitus, excess alcohol consumption, chronic renal failure, and chronic lung disease acting as independent risk factors. Most affected adults ( approximately 80%) in northeast Thailand, northern Australia, and Malaysia have >/=1 underlying diseases. Symptoms of melioidosis may be exhibited many years after exposure, commonly in association with an alteration in immune status. Manifestations of disease are extremely broad ranging and form a spectrum from rapidly life-threatening sepsis to chronic low-grade infection. A common clinical picture is that of sepsis associated with bacterial dissemination to distant sites, frequently causing concomitant pneumonia and liver and splenic abscesses. Infection may also occur in bone, joints, skin, soft tissue, or the prostate. The clinical symptoms of melioidosis mimic those of many other diseases; thus, differentiating between melioidosis and other acute and chronic bacterial infections, including tuberculosis, is often impossible. Confirmation of the diagnosis relies on good practices for specimen collection, laboratory culture, and isolation of B. pseudomallei. The overall mortality rate of infected persons is 50% in northeast Thailand (35% in children) and 19% in Australia.

  9. Accidental exposure to gas emissions from transit goods treated for pest control.

    PubMed

    Kloth, Stefan; Baur, Xaver; Göen, Thomas; Budnik, Lygia Therese

    2014-12-13

    International phytosanitary standards ISPM 15 require (since 2007) fumigation or heat treatment for shipping and storage. Those dealing with fumigated freight might be accidentally exposed. In this paper we report a series of three accidents of six storage room workers in a medium sized company regularly importing electronic production parts from abroad. Patients (n=6, aged from 32-54 yrs.) and control group (n=30, mean 40 yrs.) donated blood and urine samples. The fumigants: ethylene oxide, methyl bromide, chloropicrin, ethylene dichloride, other halo-alkanes and solvents were analyzed by headspace gas chromatography/mass spectrometry (GCMS). For the quantitation of long term exposure/s, macromolecular reaction products (hemoglobin adducts) were used (with GCMS) as molecular dosimeter; additionally 8-OHdG and circulating mtDNA (cmtDNA) were analyzed as nonspecific biological effect markers. The hemoglobin adducts N-methyl valine (MEV) and N-(2-hydroxy ethyl) valine (HEV) were elevated after exposure to the alkylating chemicals methyl bromide and ethylene oxide. Under the consideration of known elimination kinetics and the individual smoking status (biomonitored with nicotine metabolite cotinine and tobacco specific hemoglobin adduct: N-(2 cyan ethyl) valines, CEV), the data allow theoretical extrapolation to the initial protein adduct concentrations at the time of the accident (the MEV/CEV levels were from 1,616 pmol/g globin to 1,880 pmol/g globin and HEV/CEV levels from 1,407 pmol/g globin to 5,049 pmol/g globin, and correlated with inhaled 0.4-1.5 ppm ethylene oxide. These integrated, extrapolated internal doses, calculated on the basis of biological exposure equivalents, confirmed the clinical diagnosis for three patients, showing severe intoxication symptoms. Both, cmtDNA and 8-OHdG, as non-specific biomarkers of toxic effects, were elevated in four patients. The cases reported here, stress the importance of a suitable risk assessment and control measures. We

  10. Accidental exposures to blood and body fluids among health care workers in a Referral Hospital of Cameroon.

    PubMed

    Nouetchognou, Julienne Stéphanie; Ateudjieu, Jérôme; Jemea, Bonaventure; Mbanya, Dora

    2016-02-15

    Accidental exposure to blood and body fluids is a public health concern, especially among health workers and constitutes a risk of transmission of blood-borne viruses including HIV, hepatitis B virus and hepatitis C virus. The objective of this study was to determine the frequency and the post exposure management of accidental exposures to blood and body fluid among health workers in the Yaoundé University Teaching Hospital. It was a cross-sectional hospital-based study conducted from the 1st to the 30th of September 2013. Self-administered questionnaires to health workers were used to collect data on self-reported accidents, circumstances and post-exposure management. Their knowledge on accidental exposure to blood was also assessed. Data were entered and analyzed using Epi Info software version 3.5.4. Descriptive analysis was performed to measure the importance of AEB and to evaluate the risk of contamination. One hundred and fifty health workers were interviewed among which 36.7 % reported having been exposed to blood and body fluid at least once in the preceding 3 months. Splash was the most reported injury (in 60.3 % of cases), followed by needle stick (28.7 %) and cuts (10.9 %). Moreover, 43.6 % of victims were not vaccinated against HBV, 7.3 % were not wearing gloves during the accident and 41 % of splash occurs on injured skin. The majority of victims belong to the surgical Department [20 %, p = 0.2310]. None of these injuries had been reported in the registry of accidental exposure to blood. There is a high rate of accidental exposure to blood and body fluid in the daily hospital routine. Preventives measures, including wearing of protective equipment's during care and vaccination against HBV are not systematically done among health workers. Health institution should develop and provide standard operating procedures targeting surveillance of occupational risks, staff training, and supervision.

  11. Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication

    PubMed Central

    Roda, E.; Vecchio, S.; Apostoli, P.

    2016-01-01

    Introduction. Chronic poisoning may result in home setting after mercury (Hg) vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg) monitoring were performed from admission (t0), until 1 year later (t2), paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs). At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1–4.5; UHg 0.1–4.5), associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0–16.0). At t1 (two days after DMSA-mobilization test), BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes). At t2 (eight months after two cycles of DMSA chelating therapy ending), gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp.) and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes). Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring. PMID:27872646

  12. Acute accidental phosgene poisoning.

    PubMed

    Gutch, Manish; Jain, Nirdesh; Agrawal, Avinash; Consul, Suchi

    2012-04-02

    Phosgene is a highly toxic gas to which accidental exposure may occur in occupational workers. This case report describes the clinical presentation and management of accidental phosgene poisoning happened after the leakage of phosgene gas from nearby pipeline. The need to suspect phosgene gas exposure and observe such patients is crucial for life saving, especially in view of the delay in clinical deterioration observed in some patients who subsequently develop adult respiratory distress syndrome.

  13. Acute accidental phosgene poisoning

    PubMed Central

    Gutch, Manish; Jain, Nirdesh; Agrawal, Avinash; Consul, Suchi

    2012-01-01

    Phosgene is a highly toxic gas to which accidental exposure may occur in occupational workers. This case report describes the clinical presentation and management of accidental phosgene poisoning happened after the leakage of phosgene gas from nearby pipeline. The need to suspect phosgene gas exposure and observe such patients is crucial for life saving, especially in view of the delay in clinical deterioration observed in some patients who subsequently develop adult respiratory distress syndrome. PMID:22602834

  14. Urban "accidental" wetlands mediate water quality and heat exposure for homeless populations in a desert city

    NASA Astrophysics Data System (ADS)

    Palta, M.

    2015-12-01

    In urban settings where humans interact in complex ways with ecosystems, there may be hidden or unanticipated benefits (services) or harm (disservices) conferred by the built environment. We examined interactions of a highly vulnerable population, the homeless, with urban waterways and wetlands in the desert city of Phoenix, Arizona, U.S.A. Climate change models project increases in heat, droughts, and extreme floods for the southwestern U.S. These projected changes pose a number of problems for sustainability and quality of future water supply, and the ability of human populations to mitigate heat stress and avoid fatalities. Urban wetlands that are created "accidentally" (by water pooling in abandoned areas of the landscape) have many structural (e.g., soils and hydrology) and functional (e.g., high denitrification) elements that mimic natural, unaltered aquatic systems. Accidental wetland systems in the dry bed of the Salt River, fed by storm and waste water from urban Phoenix, are located within economically depressed sections of the city, and show the potential for pollutant and heat mitigation. We used a mixed-method socio-ecological approach to examine wetland ecosystem functions and the ways in which homeless populations utilize Salt River wetlands for ecosystem services. Interviews and trash surveys indicated that homeless people are accessing and utilizing the wetlands as a source of running water, for sanitary and heat mitigation services, and for recreation and habitation. Environmental monitoring demonstrated that the wetlands can provide a reliable source of running water, nutrient and pathogen removal, heat mitigation, and privacy, but they may also pose a health risk to individuals coming in contact with the water through drinking or bathing. Whether wetlands provided a net benefit vs. harm varied according to site, season, and particular service, and several tradeoffs were identified. For example, heat is highest during the summer storm season

  15. Immunological abnormalities 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed Central

    Jennings, A M; Wild, G; Ward, J D; Ward, A M

    1988-01-01

    Eighteen workers were reviewed 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). Clinical assessment showed that they were in good health. A study of several biochemical and immunological parameters in these subjects and in 15 carefully matched controls showed no difference in serum concentrations of hepatic enzymes between exposed workers and controls. Although mean serum concentrations of cholesterol and triglyceride were higher in exposed subjects than in controls, the results did not reach statistical significance. Antinuclear antibodies and immune complexes were detected significantly more frequently in the peripheral blood of workers exposed to dioxin. There was no significant difference between exposed workers and controls in the number of T lymphocytes, B lymphocytes, and helper and suppressor T cell counts in peripheral blood, but the number of natural killer cells identified by the monoclonal antibody Leu-7 was significantly higher in workers exposed to dioxin. PMID:3264183

  16. Accidental exposures to blood and body fluid in the operation room and the issue of underreporting.

    PubMed

    Nagao, Miki; Iinuma, Yoshitsugu; Igawa, Junko; Matsumura, Yasufumi; Shirano, Michinori; Matsushima, Aki; Saito, Takashi; Takakura, Shunji; Ichiyama, Satoshi

    2009-09-01

    A retrospective review of all exposure injuries affecting members of the operative care line at a single university hospital between January 2000 and December 2007 was performed. A questionnaire survey on current status of adherence to barrier precautions was also completed by 164 staff members. Of 136 exposure injuries, 87 (64.0%) were in surgeons, and 49 (36.0%) were in scrub nurses. Surgeons were most commonly injured during suturing (49, 56%), followed by "handing over sharps" (7, 8%), whereas scrub nurses were most commonly injured during "counting and sorting of sharps" (15, 41%), followed by "handing over sharps," and "splash." The questionnaire survey revealed that compliance with goggles, face shields, and double gloving was poor, and only 9% of respondents routinely used the hands-free technique. Only 22% of staff who had experienced exposure injuries reported every incident. Because circumstances of exposure injuries in operating rooms differ by profession, appropriate preventive measures should address individual situations. To reduce exposure injuries in the operating room, further efforts are required including education, mentoring, and competency training for operation personnel.

  17. Health Effects of Chronic Arsenic Exposure

    PubMed Central

    Hong, Young-Seoub; Song, Ki-Hoon; Chung, Jin-Yong

    2014-01-01

    Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments. PMID:25284195

  18. The chronic effects of sulfur mustard exposure.

    PubMed

    Rowell, Mike; Kehe, Kai; Balszuweit, Frank; Thiermann, Horst

    2009-09-01

    Whilst the acute effects of sulfur mustard have been relatively well characterised, the chronic effects of short term but significant exposures are still evolving. The approximately 30,000 Iranian victims of CW exposure from the 1980 to 1988 Iran-Iraq war who are currently being followed form a key population who are now 20 years post-exposure. The key chronic findings in this population reflect the common acute effects of sulfur mustard, and are related to the skin, eye and respiratory system. Excluding pruritus, skin changes appear to settle. Eye symptoms are slowly progressive, however a severe, rapid onset form of keratitis is seen to develop in a number of patients after a latent period of 15-20 years. The respiratory tract also shows progressive deterioration, with bronchiolitis obliterans now being considered the main pathological feature of "mustard lung". In addition, there are other potential effects of sulfur mustard exposure which become evident only in the longer term and which are being investigated, including the development of cancer, immunological and neuropsychiatric changes, and reproductive effects. Finally, a chronic effect of sulfur mustard exposure that is now becoming apparent is the wider long-term social and economic effects of these illnesses on individuals and their families.

  19. Accidental exposure to electromagnetic fields from the radar of a naval ship: a descriptive study.

    PubMed

    Moen, Bente E; Møllerløkken, Ole Jacob; Bull, Nils; Oftedal, Gunnhild; Mild, Kjell Hansson

    2013-01-01

    Part of a crew on a Norwegian naval ship was exposed to the radar waves for approximately 7 min from an American destroyer during an incident at sea in August 2012. Information about the exposure was not given by the navy. This is a description of what happened with the crew on board after this event. 14 persons had been on the ship bridge or outside on the deck during the exposure and the rest of the crew had been inside the ship. 27 persons were examined at a hospital 6-8 months after the event, as they had developeda large number of symptoms from different organ systems. They were very worried about all types of possible adverse health effects due to the incident. All were examined by an occupational physician and anophthalmologist, by an interview, clinical examinations and blood tests at the hospital. The interview of the personnel revealed that they had not experienced any major heating during the episode. Their symptoms developed days or weeks after the radar exposure. They had no objective signs of adverse health effects at the examination related to the incident. Long-term health effect from the exposure is highly unlikely. The development of different symptoms after the incident was probably due to the fear of possible health consequences. Better routines for such incidents at sea should be developed to avoid this type of anxiety.

  20. Chronic respiratory effects of indoor formaldehyde exposure

    SciTech Connect

    Krzyzanowski, M.; Quackenboss, J.J.; Lebowitz, M.D.

    1990-01-01

    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 HCHO 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.

  1. Code System for Calculating Radiation Exposure Resulting from Accidental Radioactive Releases to the Hydrosphere.

    SciTech Connect

    1982-11-18

    Version 00 LPGS was developed to calculate the radiological impacts resulting from radioactive releases to the hydrosphere. The name LPGS was derived from the Liquid Pathway Generic Study for which the original code was used primarily as an analytic tool in the assessment process. The hydrosphere is represented by the following types of water bodies: estuary, small river, well, lake, and one-dimensional (1-D) river. LPGS is designed to calculate radiation dose (individual and population) to body organs as a function of time for the various exposure pathways. The radiological consequences to the aquatic biota are estimated. Several simplified radionuclide transport models are employed with built-in formulations to describe the release rate of the radionuclides. A tabulated user-supplied release model can be input, if desired. Printer plots of dose versus time for the various exposure pathways are provided.

  2. Analysis for Plasma Protein Biomarkers Following an Accidental Human Exposure to Sulfur Mustard

    DTIC Science & Technology

    2008-01-01

    be described in brief here. Within 2 h of the munition’s destruction, one of the individuals (a 35-year- old male) noticed a tingling sensation on one...arm and then showered. The next morning (approximately 14 h after the liquid contact), he had developed painful areas of the hand with noticeable...including the lack of pain during the chemical exposure, the time sequence of the development of blisters, and the "string of pearls" pattern of the blisters

  3. Biomass smoke exposure and chronic lung disease.

    PubMed

    Assad, Nour A; Kapoor, Vidit; Sood, Akshay

    2016-03-01

    Approximately 3 billion people worldwide rely on coal and biomass fuel for cooking and heating. Biomass smoke exposure is associated with several chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome, usual interstitial pneumonitis, hut lung, and bronchial anthracofibrosis. Household air pollution primarily from biomass smoke is the biggest risk factor for COPD worldwide. Despite the significant burden of biomass smoke-related respiratory disease, the exposure is still underappreciated worldwide, especially in high-income countries. Recent literature highlights the immunoinflammatory differences between biomass smoke-related COPD and tobacco smoke-related COPD that may lead to better understanding of the differences in the clinical phenotypes between the two entities, suggests an association with the recently recognized asthma-COPD overlap syndrome, and elucidates the burden of disease in high-income countries. The current review focuses on the association between biomass smoke and common chronic respiratory diseases, discuss differences between biomass smoke-related COPD and tobacco smoke-related COPD, highlights chronic respiratory diseases that are specific for biomass smoke exposure such as hut lung and bronchial anthracofibrosis, and discusses the known impact of beneficial interventions.

  4. Accidental explosions

    SciTech Connect

    Medard, L.A.

    1989-01-01

    This book presents a survey of accidental explosions, their nature and their causes. It covers the physical and chemical conditions governing accidental explosions, whether in the gas phase, or in the liquid or solid state. The theoretical background of the kinetics and thermochemistry of explosions is outlined, followed by a detailed study of the explosion and detonation properties of both gas and condensed explosives. The author surveys a wide variety of substances in daily use in industry which can give rise to accidental explosions. Their properties and hazards are spelt out in detail, the discussion drawing on a long history of sometimes catastrophic accidents. Includes case studies, tables of physical and chemical data.

  5. Hydrocarbon exposure and chronic renal disease.

    PubMed

    Asal, N R; Cleveland, H L; Kaufman, C; Nsa, W; Nelson, D I; Nelson, R Y; Lee, E T; Kingsley, B

    1996-01-01

    The study objective was to investigate further the potential role of long-term exposure to hydrocarbons (HCs) in the development of idiopathic chronic glomerulopathy (ICG) using a more refined measurement of HC exposure. A total of 321 pairs of cases and controls, matched by age, gender, and geographical area, were assembled. A detailed questionnaire was blindly administered to cases and controls to collect information on occupational and medical history and sociodemographic data. By integrating quantified measurements of HC exposure from a variety of sources with each subject's occupational history, a lifetime HC exposure score could be estimated and expressed in parts per million (ppm). Cases had an hydrocarbon exposure mean score of 165 ppm (median 48 ppm) as compared to 162 ppm (median 43 ppm) for controls (P = 0.757). When using hydrocarbon exposure as a dichotomous variable with a cutoff point at 100 ppm, cases had a higher proportion of exposed than controls, but the difference was not statistically significant at the 0.05 level, even after controlling for possible confounders through logistic regression. Subgroup analyses showed mixed results. In most subgroups differences between cases and controls tended to become significant when hydrocarbon was used as a dichotomous variable. Results from this study do not sufficiently support the hypothesized association of HC exposure and ICG in general. Subgroup analyses need further investigations. Efforts to generate accurate estimates of lifetime HC exposure should be emphasized for future investigations.

  6. Pathology related to chronic arsenic exposure.

    PubMed Central

    Centeno, Jose A; Mullick, Florabel G; Martinez, Leonor; Page, Norbert P; Gibb, Herman; Longfellow, David; Thompson, Claudia; Ladich, Elena R

    2002-01-01

    Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water. PMID:12426152

  7. Evaluating the Radiation From Accidental Exposure During a Nondestructive Testing Event.

    PubMed

    Ting, Chien-Yi; Wang, Hsin-Ell; Lin, Jao-Perng; Lin, Chun-Chih

    2015-08-01

    Industrial radiography is a common nondestructive testing (NDT) method used in various industries. An investigation was conducted for a 1999 incident in Taiwan where two workers (Operators A and B) were accidently exposed to an unshielded Ir source while conducting industrial radiography. Operators A and B experienced acute close-range radiation exposure to a source of Ir for 3 h at a strength of 2.33 × 10 Bq. The health of mammary glands, bone marrow, thyroid glands, eyes, and genital organs of these two workers after radiation exposure was examined. Subsequently, Operator A experienced severe radiation injury, including tissue necrosis and keratinization in the fingers, chromosomal abnormalities, reduced blood cell count, diffuse hyperplasia of the thyroid gland, opaque spots in the crystalline lens, and related radiation effects. The results showed that the left index finger and thumb, eyes, and gonads of Operator A were exposed to a radiation dose of about 369-1,070, 23.1-67.4, 2.4-5.3, and 4.2-11.6 Gy, respectively. Effective dose for Operator A was estimated to range from 6.9 to 18.9 Sv. The left fingers, thumb, eyes, and gonads of Operator B were exposed to a radiation dose of 184.9-646.2, 11.8-40.7, 0.49-3.33, and 0.72-7.18 Gy, respectively, and his effective dose was between 2.5 and 11.5 Sv. This accident indicated a major flaw in the control and regulation of radiation safety for conducting NDT industrial radiography in 1999; however, similar problems still exist. Modifications of the Ionizing Radiation Protection Act in Taiwan are suggested in this study to regulate the management of NDT industries, continually educate the NDT workers in radiation safety, and enact notification provisions for medical care systems toward acute radiation exposure events.

  8. Collective radiation biodosimetry for dose reconstruction of acute accidental exposures: a review.

    PubMed Central

    Pass, B

    1997-01-01

    Quantification of the biologically relevant dose is required to establish cause and effect between radiation detriment or burden and important biological outcomes. Most epidemiologic studies of unanticipated radiation exposure fail to establish cause and effect because researchers have not been able to construct a valid quantification of dose for the exposed population. However, no one biodosimetric technique (biophysical or biological) meets all the requirements of an ideal dosimeter. This paper reviews how the collection of biodosimetric data for victims of radiation accidents can be used to create a dosimetric "gold standard." Particular emphasis is placed on the use of electron spin resonance, a standard for radiation accident dosimetry. As an example of this technique, a review will be presented of a previously reported study of an individual exposed to a 60Co sterilization source. PMID:9467051

  9. Appearance of pseudo-Pelger Huet anomaly after accidental exposure to ionizing radiation in vivo.

    PubMed

    Goans, Ronald E; Iddins, Carol J; Christensen, Doran; Wiley, Albert; Dainiak, Nicholas

    2015-03-01

    To evaluate the morphology of formed elements of human blood after exposure to ionizing radiation in vivo, archival smears of peripheral blood from eight individuals involved in the 1958 Y-12 criticality accident at Oak Ridge, Tennessee, were examined manually by light microscopy. For each case, increased interlobar bridging was observed in nuclei of the myeloid cells, many of which were bilobed and morphologically similar to Pelger Huet (PH) cells. The high-dose group (n = 5, 2.98-4.61 Gy-Eq) exhibited 13.0 ± 0.85% PH cells (mean ± SEM) in the neutrophil population compared to 6.8 ± 1.6% in the low-dose group (n = 3, 0.29-0.86 Gy-Eq; p = 0.008). An age- and gender-matched control group (n = 8) exhibited 3.6 ± 0.9% PH cells. Results of a one-way ANOVA show that the high-dose group is statistically different from both the low-dose group and the control group (p = 0.002). However, the low-dose group is not statistically different from the control group (p = 0.122). The mean number of nuclear lobes in blood neutrophils was also enumerated as a function of time after exposure and was found to be diminished, consistent with incomplete nuclear segmentation that is characteristic of the Pelger Huet anomaly (PHA). In contrast to these changes in myeloid cells, the morphology of erythrocytes and platelets appeared to be normal. The authors conclude that ionizing radiation induces abnormal morphology of circulating neutrophils, which is similar to the pseudo-PHA that is acquired in disorders such as myelodysplastic syndrome, acute myeloid leukemia, and leukemoid reactions. Potential molecular mechanisms by which radiation induces this morphological change are discussed. From this cohort, the biomarker appears to be present early post-accident (<9 h) and stable at least up to 16 y post-accident. Assessment of circulating pseudo-Pelger Huet cells is being investigated as a potential biodosimetric tool.

  10. PM₁₀ exposure and non-accidental mortality in Asian populations: a meta-analysis of time-series and case-crossover studies.

    PubMed

    Park, Hye Yin; Bae, Sanghyuk; Hong, Yun-Chul

    2013-01-01

    We investigated the association between particulate matter less than 10 µm in aerodynamic diameter (PM₁₀) exposure and non-accidental mortality in Asian populations by meta-analysis, using both time-series and case-crossover analysis. Among the 819 published studies searched from PubMed and EMBASE using key words related to PM₁₀ exposure and non-accidental mortality in Asian countries, 8 time-series and 4 case-crossover studies were selected for meta-analysis after exclusion by selection criteria. We obtained the relative risk (RR) and 95% confidence intervals (CI) of non-accidental mortality per 10 µg/m³ increase of daily PM₁₀ from each study. We used Q statistics to test the heterogeneity of the results among the different studies and evaluated for publication bias using Begg funnel plot and Egger test. Testing for heterogeneity showed significance (p<0.001); thus, we applied a random-effects model. RR (95% CI) per 10 µg/m³ increase of daily PM₁₀ for both the time-series and case-crossover studies combined, time-series studies relative risk only, and case-crossover studies only, were 1.0047 (1.0033 to 1.0062), 1.0057 (1.0029 to 1.0086), and 1.0027 (1.0010 to 1.0043), respectively. The non-significant Egger test suggested that this analysis was not likely to have a publication bias. We found a significant positive association between PM₁₀ exposure and non-accidental mortality among Asian populations. Continued investigations are encouraged to contribute to the health impact assessment and public health management of air pollution in Asian countries.

  11. Chronic respiratory effects of indoor formaldehyde exposure

    SciTech Connect

    Krzyzanowski, M.; Quackenboss, J.J.; Lebowitz, M.D. )

    1990-08-01

    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 during two 1-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 HCHO levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR decreased linearly with HCHO exposure, with the estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children. The effects in asthmatic children exposed to HCHO below 50 ppb were greater than in healthy ones. The effects in adults were less evident: decrements in PEFR due to HCHO over 40 ppb were seen only in the morning, and mainly in smokers.

  12. Retrospective dosimetry related to chronic environmental exposure

    NASA Technical Reports Server (NTRS)

    Degteva, M. O.; Kozheurov, V. P.; Tolstykh, E. I.; Neta, R. (Principal Investigator)

    1998-01-01

    Radioactive contamination of the environment occurred in the early fifties as a result of the releases from the Mayak plutonium production complex (Southern Urals, Russia). The releases of liquid wastes into the Techa river resulted in chronic exposure of 30,000 residents of the riverside communities. Since 1951 90Sr body burdens have been measured for over half of this cohort. This paper presents the analysis of data on 90Sr in humans and describes the reconstruction of internal doses for these people.

  13. Determination of VX-G analogue in red blood cells via gas chromatography-tandem mass spectrometry following an accidental exposure to VX.

    PubMed

    McGuire, Jeffrey M; Taylor, James T; Byers, Christopher E; Jakubowski, Edward M; Thomson, Sandra M

    2008-01-01

    A sensitive method for determining exposure to the chemical warfare agent VX is described in which the biomarker ethyl methylphosphonofluoridate (VX-G) is measured in red blood cells (RBCs) following treatment with fluoride ion using isotope-dilution gas chromatography-tandem mass spectrometry. The analyte was isolated via solid-phase extraction and detected using ammonia chemical ionization in the multiple reaction monitoring mode. A good linear relationship was obtained in the quantitative concentration range of 4 ng/mL to 1000 ng/mL with an absolute detection limit of < 1 pg on column. The method has been applied to the analysis of RBCs from a laboratory worker accidentally exposed to VX vapor. Detection and quantitation of VX-G were possible in samples taken as late as 27 days following exposure.

  14. Fall-related self-efficacy, not balance and mobility performance, is related to accidental falls in chronic stroke survivors with low bone mineral density

    PubMed Central

    Pang, Marco Y.C.; Eng, Janice J.

    2011-01-01

    Introduction Chronic stroke survivors with low bone mineral density (BMD) are particularly prone to fragility fractures. The purpose of this study was to identify the determinants of balance, mobility and falls in this sub-group of stroke patients. Methods Thirty nine chronic stroke survivors with low hip BMD (T-score <-1.0) were studied. Each subject was evaluated for: balance, mobility, leg muscle strength, spasticity, and falls-related self-efficacy. Any falls in the past 12 months were also recorded. Multiple regression analysis was used to identify the determinants of balance and mobility performance whereas logistic regression was used to identify the determinants of falls. Results Multiple regression analysis revealed that after adjusting for basic demographics, falls-related self-efficacy remained independently associated with balance/mobility performance (R2=0.494, P<0.001). Logistic regression showed that falls-related self-efficacy, but not balance and mobility performance, was a significant determinant of falls (odds ratio: 0.18, P=0.04). Conclusions Falls-related self-efficacy, but not mobility and balance performance, was the most important determinant of accidental falls. This psychological factor should not be overlooked in the prevention of fragility fractures among chronic stroke survivors with low hip BMD. PMID:18097709

  15. Chronic lead exposure reduces junctional resistance at an electrical synapse.

    PubMed

    Audesirk, G; Audesirk, T

    1984-01-01

    Both acute and chronic lead exposure have been found to inhibit transmission at chemical synapses, possibly by interfering with inward calcium current. We have found that chronic lead exposure slightly reduces input resistance and greatly reduces the junctional resistance between two strongly electrically coupled neurons in the pond snail Lymnaea stagnalis. The net effect is to increase the strength of electrical coupling. A reduction in gap junctional resistance would also be expected to increase the flow of small molecules between cells. However, Lucifer Yellow injections did not reveal dye-coupling between the cells. Lead exposure also increases the capacitance of the neurons.

  16. Chronic nicotine exposure exacerbates acute renal ischemic injury

    PubMed Central

    Grifoni, Samira; Clark, Jeb S.; Csongradi, Eva; Maric, Christine; Juncos, Luis A.

    2011-01-01

    Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury. PMID:21511693

  17. Chronic nicotine exposure exacerbates acute renal ischemic injury.

    PubMed

    Arany, Istvan; Grifoni, Samira; Clark, Jeb S; Csongradi, Eva; Maric, Christine; Juncos, Luis A

    2011-07-01

    Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.

  18. TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS

    EPA Science Inventory

    Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukary...

  19. TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS

    EPA Science Inventory

    Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukary...

  20. Renal responses to chronic cold exposure.

    PubMed

    Sun, Zhongjie; Zhang, Zhonge; Cade, Robert

    2003-01-01

    The aim of this study was to assess our hypothesis that the release of antidiuretic hormone (ADH), the renal concentrating response to ADH, or both is decreased by prolonged cold exposure. Six groups (n = 6/group) of rats were used. Three groups were exposed to cold (5 degrees C), whilethe remaining three groups were kept at room temperature (25 degrees C). It was found that urine osmolality decreased significantly and serum osmolality increased significantly during cold exposure. The ratio of water/food intake was not affected by prolonged cold exposure. However, prolonged cold exposure increased the ratio of urine output/food intake in the cold-exposed rats, indicating that more urine flow is required by the cold-exposed rats to excrete the osmotic substance at a given food intake. The difference between water intake and urine output decreased significantly in the cold-exposed rats. Thus, prolonged cold exposure increases water loss from excretion. Renal concentrating responses to 24-h dehydration and Pitressin were decreased significantly in the cold-exposed rats. Plasma ADH levels remained unchanged, but renal ADH receptor (V2 receptor) mRNA was decreased significantly in the cold-exposed rats. The results strongly support the conclusion that cold exposure increases excretive water loss, and this may be due to suppression of renal V2 receptors rather than inhibition of ADH release.

  1. Regulation of adenosine transport by acute and chronic ethanol exposure

    SciTech Connect

    Nagy, L.E.; Casso, D.; Diamond, I.; Gordon, A.S. )

    1989-02-09

    Chronic exposure to ethanol results in a desensitization of adenosine receptor-stimulated cAMP production. Since adenosine is released by cells and is known to desensitize its own as well as other receptors, it may be involved in ethanol-induced desensitization of adenosine receptor function. Therefore, we have examine the acute and chronic effects of ethanol on the transport of adenosine via the nucleoside transport. Acute exposure to ethanol caused an inhibition of adenosine uptake in S49 lymphoma cells. This decrease in uptake resulted in accumulation of extracellular adenosine after ethanol exposure. The effect of ethanol was specific to nucleoside transport. Uptake of uridine, also transported by the nucleoside transporter, was inhibited by ethanol to the same degree as adenosine uptake, while neither isoleucine nor deoxyglucose uptake was altered by ethanol treatment. Inhibition of adenosine uptake by ethanol was non-competitive and dependent on the concentration of ethanol. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol. There was no longer an acute inhibition of adenosine uptake, nor was these accumulation of extracellular adenosine. Chronic ethanol exposure also resulted in a decrease in the absolute rate of adenosine uptake. Binding studies using a high affinity lignad for the nucleoside transporter, nitrobenzylthioinosine (NBMPR), indicate that this decreased uptake was due to a decrease in the maximal number of binding sites. These ethanol-induced changes in adenosine transport may be important for the acute and chronic effects of ethanol.

  2. Exposure-response relationships between occupational exposures and chronic respiratory illness: a community-based study.

    PubMed

    Xu, X; Christiani, D C; Dockery, D W; Wang, L

    1992-08-01

    Data from a random sample of 3,606 adults 40 to 69 yr of age residing in Beijing, China, were analyzed to investigate the association of reported occupational exposures to dusts and gases/fumes with the prevalence of chronic respiratory symptoms and level of pulmonary function. The prevalence of occupational dust exposure was 32%, and gas or fume exposure, 19%. After we adjusted for age, sex, area of residence, smoking status, coal stove heating, and education, an increased prevalence of chronic phlegm and breathlessness was significantly related to both types of exposures. Chronic cough was significantly related only to dust exposure, and persistent wheeze only to fume exposure. The global estimates of the relative odds of the four symptoms were 1.30 (95% CI [confidence interval] 1.09 to 1.48) and 1.27 (95% CI 1.09 to 1.48), respectively, for dusts and for gases/fumes. These two occupational exposures are associated with chronic respiratory symptoms independent of smoking, gender, and each other. There was an increasing prevalence of each symptom with increasing dust and fume exposure, represented by the index of cumulative exposure duration and exposure intensity. Linear trends for increased prevalence of chronic bronchitis and breathlessness were significant for both exposures, while the linear trend for wheeze was only significant for gases/fumes. Among subjects who did not report using coal stove heating, dust exposure was a significant predictor for FEV1, FEV1/FVC, FEF25-75, and peak expiratory flow rate (PEFR). There was also a significant decrease for FEV1 and FVC with increase of gas/fume exposure levels. Both current and former smokers appeared to be more susceptible to the effect of dusts than the never smokers.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Comprehensive default methodology for the analysis of exposures to mixtures of chemicals accidentally released to the atmosphere

    SciTech Connect

    Craig, D.K.; Baskett, R.L.; Powell, T.J.; Davis, J.S.; Dukes, L.L.; Hansen, D.J.; Petrocchi, A.J.; Sutherland, P.J.

    1997-07-01

    Safety analysis of Department of Energy (DOE) facilities requires consideration of potential exposures to mixtures of chemicals released to the atmosphere. Exposure to chemical mixtures may lead to additive, synergistic, or antagonistic health effects. In the past, the consequences of each chemical have been analyzed separately. This approach may not adequately protect the health of persons exposed to mixtures. However, considerable time would be required to evaluate all possible mixtures. The objective of this paper is to present reasonable default methodology developed by the EFCOG Safety Analysis Working Group Nonradiological Hazardous Material Subgroup (NHMS) for use in safety analysis within the DOE Complex.

  4. Psychologic sequelae of chronic toxic waste exposure

    SciTech Connect

    Foulks, E.; McLellen, T. )

    1992-02-01

    Exposure to toxic industrial substances has been a topic of increasing concern to environmentalists, government agencies, industrial engineers, and medical specialists. Our study focuses on the psychologic symptom responses of a community to perceived long-term exposure to toxic waste products. We compared their symptom clusters, as shown by their responses to questions on the Hopkins Symptom Checklist-90 Item (SCL-90) and the Social Adjustment Scale (SAS), with symptom levels of normal and depressed subjects. Issues of media coverage, litigation, and potential for compensation complicate the psychiatric epidemiology of the subject.

  5. Re-exposure of mallards to selenium after chronic exposure

    SciTech Connect

    Heinz, G.H. . Patuxent Wildlife Research Center)

    1993-09-01

    Adult male mallards (Anas platyrhynchos) were fed a control diet or a diet containing 15 ppm selenium as seleno-D,L-methionine for 21 weeks. After this initial exposure, the mallards were fed untreated food for 12 weeks, then were re-exposed to selenium at 100 ppm for five weeks. During re-exposure to 100 ppm selenium, the birds that had previously been exposed to 15 ppm selenium and those that had not previously been exposed did not differ in percentage of mortality, weight loss in survivors, selenium concentrations in the livers of survivors, or selenium concentrations in the livers of birds that died. When the data from the birds that had previously been exposed to 15 ppm selenium were combined in the livers of birds that had died on the 100-ppm selenium treatment did not differ from the concentrations in the livers of birds that had survived.

  6. User's manual for LPGS: a computer program for calculating radiation exposure resulting from accidental radioactive releases to the hydrosphere

    SciTech Connect

    White, J.E.; Eckerman, K.F.

    1982-11-01

    The LPGS computer program was developed to calculate the radiological impacts resulting from radioactive releases to the hydrosphere. The hydrosphere is represented by the following types of water bodies: estuary, small river, well, lake, and one-dimensional (1-D) river. The program is principally designed to calculate radiation dose (individual and population) to body organs as a function of time for the various exposure pathways. The radiological consequences to the aquatic biota is estimated. Several simplified radionuclide transport models are employed with built-in formulations to describe the release rate of the radio-nuclides. Optionally, a tabulated user-supplied release model can be input. Printer plots of dose versus time for the various exposure pathways are provided.

  7. Chronic Ambient Hydrogen Sulfide Exposure and Cognitive Function

    PubMed Central

    Reed, Bruce R.; Crane, Julian; Garrett, Nick; Woods, David L.; Bates, Michael N.

    2014-01-01

    Background Exposures to hydrogen sulfide gas (H2S) have been inconclusively linked to a variety of negative cognitive outcomes. We investigated possible effects on cognitive function in an urban population with chronic, low-level exposure to H2S. Methods Participants were 1,637 adults, aged 18-65 years from Rotorua city, New Zealand, exposed to ambient H2S from geothermal sources. Exposures at homes and workplaces were estimated from data collected by summer and winter H2S monitoring networks across Rotorua in 2010/11. Metrics for H2S exposure at the time of participation and for exposure over the last 30 years were calculated. H2S exposure was modeled both as continuous variables and as quartiles of exposure covering the range of 0 – 64 ppb (0-88 μg/m3). Outcomes were neuropsychological tests measuring visual and verbal episodic memory, attention, fine motor skills, psychomotor speed and mood. Associations between cognition and measures of H2S exposure were investigated with multiple regression, while covarying demographics and factors known to be associated with cognitive performance. Results The consistent finding was of no association between H2S exposure and cognition. Quartiles of H2S exposure had a small association with simple reaction time: higher exposures were associated with faster response times. Similarly, for digit symbol, higher H2S exposures tended to be marginally associated with better performance. Conclusion The results provide evidence that chronic H2S exposure, at the ambient levels found in and around Rotorua, is not associated with impairment of cognitive function. PMID:24548790

  8. Chronic ambient hydrogen sulfide exposure and cognitive function.

    PubMed

    Reed, Bruce R; Crane, Julian; Garrett, Nick; Woods, David L; Bates, Michael N

    2014-01-01

    Exposures to hydrogen sulfide gas (H2S) have been inconclusively linked to a variety of negative cognitive outcomes. We investigated possible effects on cognitive function in an urban population with chronic, low-level exposure to H2S. Participants were 1637 adults, aged 18-65 years from Rotorua city, New Zealand, exposed to ambient H2S from geothermal sources. Exposures at homes and workplaces were estimated from data collected by summer and winter H2S monitoring networks across Rotorua in 2010/11. Metrics for H2S exposure at the time of participation and for exposure over the last 30 years were calculated. H2S exposure was modeled both as continuous variables and as quartiles of exposure covering the range of 0-64 ppb (0-88 μg/m(3)). Outcomes were neuropsychological tests measuring visual and verbal episodic memory, attention, fine motor skills, psychomotor speed and mood. Associations between cognition and measures of H2S exposure were investigated with multiple regression, while covarying demographics and factors known to be associated with cognitive performance. The consistent finding was of no association between H2S exposure and cognition. Quartiles of H2S exposure had a small association with simple reaction time: higher exposures were associated with faster response times. Similarly, for digit symbol, higher H2S exposures tended to be marginally associated with better performance. The results provide evidence that chronic H2S exposure, at the ambient levels found in and around Rotorua, is not associated with impairment of cognitive function. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Accidental injuries associated with nonhuman primate exposure at two regional primate research centers (USA): 1988-1993.

    PubMed

    bin Zakaria, M; Lerche, N W; Chomel, B B; Kass, P H

    1996-06-01

    Although occupationally acquired zoonoses of nonhuman primates have been well documented, the epidemiology of work-related injuries associated with occupational exposure to nonhuman primates has not been studied. To investigate such injuries, we retrospectively reviewed injury records at one regional primate research center and distributed a self-administered, anonymous questionnaire to at-risk personnel at two centers. Records of bite, animal-inflicted scratch, needlestick, cut, and mucous membrane exposure injuries were reviewed at one center for the 5-year period 1988 to 1993 to determine incidence and frequency of injuries and to identify possible risk factors. A total of 261 injuries were reported during this period, with an annual incidence for all injuries combined ranging from 43.5 to 65.5 injuries per 100,000 person workdays (pwd) at risk. For specific injuries the highest incidence was observed for animal-inflicted scratches and bites, with a rate of 82 and 81 per 100,000 pwd respectively. The job category Veterinary Resident was found to have the highest incidence for needlestick injuries (547 per 100,000 pwd), scratches (239 per 100,000 pwd), and cuts (171 per 100,000 pwd). The highest rates for bites were observed in the job categories Animal Health Technician and Animal Technician, with 171 and 150 per 100,000 pwd respectively; the category Staff Veterinarian had the highest rate of mucous membrane exposures (71 per 100,000 pwd). The frequency of all injuries was greatest in personnel employed < or = 2 years. Questionnaire responses indicated that having > 20 h per week of contact with nonhuman primates or contact with more than 50 nonhuman primates per week was associated with a significantly increased risk of bites, animal-inflicted scratches, needlesticks, and mucous membrane exposures. In addition, data analysis indicated that under-reporting of work-related injuries was high; 59% of scratches, 50% of mucous membrane exposures, 45% of cuts, 37% of

  10. Neurotoxicity From Chronic Exposure to Depleted Uranium

    DTIC Science & Technology

    2006-04-01

    these response magnitudes. This suggests that UO2 +2 does not possess Ca+2-mimetic properties, but it could also be explained if the...intrasynaptosomal UO2 +2 concentrations did not achieve sufficient levels during the acute exposure to manifest such an effect. The uranium species involved in the...effect on glutamate exocytosis is not known. Uranyl ion ( UO2 +2) – the most common form produced in the body from all forms of the metal – is

  11. Re-exposure of mallards to selenium after chronic exposure

    USGS Publications Warehouse

    Heinz, G.H.

    1993-01-01

    Adult male mallards (Anas platyrhynchos) were fed a control diet or a diet containing 15 ppm selenium as seleno-D,L-methionine for 21 weeks. After this initial exposure, the mallards were fed untreated food for 12 weeks, then were re-exposed to selenium at 100 ppm for five weeks. During re-exposure to 100 ppm selenium, the birds that had previously been exposed to 15 ppm selenium and those that had not previously been exposed did not differ in percentage of mortality (14.7 and 14.3%), weight loss in survivors (39.3 and 41.20%), selenium concentrations in the livers of survivors (35 and 53 ppm, wet weight), or selenium concentrations in the livers of birds that died (35 and 40 ppm, respectively). When the data from the birds that had previously been exposed to 15 ppm selenium were combined with the data from the birds that had not previously been exposed, selenium concentrations in the livers of birds that had died on the 100-ppm selenium treatment (38 ppm) did not differ from the concentrations in the livers of birds that had survived (43 ppm).

  12. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    PubMed

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-06-15

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother.

  13. Chronic boron exposure and human semen parameters.

    PubMed

    Robbins, Wendie A; Xun, Lin; Jia, Juan; Kennedy, Nola; Elashoff, David A; Ping, Liu

    2010-04-01

    Boron found as borates in soil, food, and water has important industrial and medical applications. A panel reviewing NTP reproductive toxicants identified boric acid as high priority for occupational studies to determine safe versus adverse reproductive effects. To address this, we collected boron exposure/dose measures in workplace inhalable dust, dietary food/fluids, blood, semen, and urine from boron workers and two comparison worker groups (n=192) over three months and determined correlations between boron and semen parameters (total sperm count, sperm concentration, motility, morphology, DNA breakage, apoptosis and aneuploidy). Blood boron averaged 499.2 ppb for boron workers, 96.1 and 47.9 ppb for workers from high and low environmental boron areas (p<0.0001). Boron concentrated in seminal fluid. No significant correlations were found between blood or urine boron and adverse semen parameters. Exposures did not reach those causing adverse effects published in animal toxicology work but exceeded those previously published for boron occupational groups.

  14. Clinical Signs and Pathology of Accidental Monensin Poisoning in Sheep

    PubMed Central

    Nation, P. N.; Crowe, S. P.; Harries, W. N.

    1982-01-01

    The clinical signs and postmortem findings in sheep from two flocks accidentally poisoned with monensin are described. Clinical signs began within 24 hours of exposure to monensin. In the acute stages they consisted of lethargy, stiffness, muscular weakness, a stilted gait and recumbency. Feed refusal was seen in one flock but not in the second. Subacute to chronic clinical signs were decreased muscle volume of the rump and thigh. When forced to run, chronically affected sheep had a stilted, stiff legged, rocking horse gait. Gross postmortem changes were not always visible. Where visible, they affected skeletal muscles and consisted of pale streaking, with atrophy in the chronic stages. Lesions were most severe in muscles of the rump and hind limbs. Microscopically myofiber swelling and hyalinization were seen with interstitial mononuclear cell reaction and extensive sarcoplasmic mineralization in some cases. Chronic lesions consisted of fibrosis and myofiber atrophy. In lambs less than one month old, diffuse gastrointestinal hemorrhage was the only finding. PMID:17422198

  15. 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.
    ...

  16. 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…

  17. 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.
    ...

  18. Chronic dysphagia and trigeminal anesthesia after trichloroethylene exposure

    SciTech Connect

    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)

  19. Review of medical findings in a Marshallese population twenty-six years after accidental exposure to radioactive fallout

    SciTech Connect

    Conard, R.A.; Paglia, D.E.; Larsen, P.R.

    1980-01-01

    In March 1954, radioactive debris from a thermonuclear weapon test at Bikini Atoll deviated from predicted trajectories and contaminated several atolls in the northern Marshall Islands. As a result, 239 native inhabitants of these islands along with 28 American servicemen and 23 Japanese fishermen received variably severe exposures to diverse ionizing radiations. Fallout material consisted largely of mixed fission products with small amounts of neutron-induced radionuclides and minimal amounts of fissionable elements, producing a complex spectrum of electromagnetic and particulate radiation. Individuals were exposed to deeply penetrating, whole-body gamma irradiation, to internal radiation emitters assimilated either by inhalation or by ingestion of contaminated water and food, and to direct radiation from material accumulating on body surfaces. That accident initiated a cascade of events, medical, social and political, which continue in varying forms to this day. Most of these have been discussed in the open medical literature and in periodic reports issued by the medical team headquartered at Brookhaven National Laboratory. This report attempts to summarize some of the principal findings of medical significnce that have been observed during the subsequent 26 years with particular emphasis on the last six years.

  20. Does Accidental Overcorrection of Symptomatic Hyponatremia in Chronic Heart Failure Require Specific Therapeutic Adjustments for Preventing Central Pontine Myelinolysis?

    PubMed Central

    De Vecchis, Renato; Noutsias, Michel; Ariano, Carmelina; Cesaro, Arturo; Cioppa, Carmela; Giasi, Anna; Maurea, Nicola

    2017-01-01

    This review aims at summarizing essential aspects of epidemiology and pathophysiology of hyponatremia in chronic heart failure (CHF), to set the ground for a practical as well as evidence-based approach to treatment. As a guide through the discussion of the available evidence, a clinical case of hyponatremia associated with CHF is presented. For this case, the severe neurological signs at presentation justified an emergency treatment with hypertonic saline plus furosemide, as indicated. Subsequently, as the neurological emergency began to subside, the reversion of the trend toward hyponatremia overcorrection was realized by continuous infusion of hypotonic solutions, and administration of desmopressin, so as to prevent the very feared risk of an osmotic demyelination syndrome. This very disabling complication of the hyponatremia correction is then briefly outlined. Moreover, the possible advantages related to systematic correction of the hyponatremia that occurs in the course of CHF are mentioned. Additionally, the case of tolvaptan, a vasopressin receptor antagonist, is concisely presented in order to underline the different views that have led to different norms in Europe with respect to the USA or Japan as regards the use of this drug as a therapeutic resource against the hyponatremia. PMID:28270885

  1. Chronic exposure to volcanic environments and chronic bronchitis incidence in the Azores, Portugal.

    PubMed

    Amaral, André Filipe Santos; Rodrigues, Armindo Santos

    2007-03-01

    The village of Furnas, like other active volcanic areas in the world, exhibits high levels of hazardous gases. We aimed to investigate the existence of a possible association between chronic exposure to volcanic sulfur gases and chronic bronchitis. To investigate this, we used two populations, one exposed to active manifestations of volcanism (Furnas) and another from an area where no volcanic activity took place for over three million years (Santa Maria), both in the Azores. We used data on the incidence of chronic bronchitis among both populations (1991-2001), obtained from the records of each local health center, and population denominators from censuses carried out in 1991 and 2001, using five age-groups. We also estimated relative risks and mean annual age-standardized rates of chronic bronchitis incidence. Incidence rates were extremely higher in the volcanically active area for both sexes, and especially in the youngest groups. Accordingly, the risk of chronic bronchitis for the people living in the volcanically active area was extremely higher (males RR=3.99; females RR=10.74) when compared to those living in the volcanically inactive area. Comparison of chronic bronchitis incidence rates between both populations suggests an association between this disease and the chronic exposure to the volcanically active environment, with all its hazardous gases like hydrogen sulfide and sulfur dioxide. These findings may help health officials to better advice people inhabiting volcanic areas, or others with high levels of sulfur gases, on how to prevent and minimize the risks of chronic bronchitis.

  2. Global quantification of γH2AX as a triage tool for the rapid estimation of received dose in the event of accidental radiation exposure.

    PubMed

    Viau, Muriel; Testard, Isabelle; Shim, Grace; Morat, Luc; Normil, Marie D; Hempel, William M; Sabatier, Laure

    2015-11-01

    The phosphorylation of the H2AX histone to form γH2AX foci has been shown to be an accurate biomarker of ionizing radiation exposure. It is well established that there is a one-to-one correlation between the number of γH2AX foci and radiation-induced double strand breaks in cellular DNA, which can be translated to the received dose. However, manual counting of foci is time-consuming, and cannot accommodate high throughput analysis required to obtain rapid results for medical triage purposes in the case of large-scale accidental exposure. Furthermore, the accuracy of γH2AX measurements could potentially be compromised by delays between the time of exposure and analysis of results, as well as inter-cellular and inter-individual variability of this biological response. To evaluate more rapid approaches of quantifying γH2AX for use in an emergency situation, and to determine the impact of inter-individual variability, we compared two methods of global γH2AX fluorescence quantification (low magnification immunofluorescence microscopy and flow cytometry) to the well-established γH2AX foci scoring method in human primary fibroblasts. All three approaches were well correlated, indicating that global γH2AX fluorescence measurements are suitable for dose estimation. For rapid triage in an emergency situation, we propose the use of flow cytometry, as it is more highly correlated with foci scoring and because of the speed and ease of the method. Dose response curves (0.25-6Gy) using flow cytometry measurements showed that inter-individual variability in global γH2AX fluorescence is statistically insignificant at 4h post-irradiation. Based on these data, we propose calibration curves that can be applied to populations exposed to moderate radiation doses to estimate individual received doses, independent of individual radiosensitivity, at this specific time point post-irradiation using human fibroblasts and lymphocytes. Furthermore, we define three triage categories that

  3. 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

  4. 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

  5. Does chronic exposure to mobile phones affect cognition?

    PubMed

    Mohan, Mamta; Khaliq, Farah; Panwar, Aprajita; Vaney, Neelam

    2016-01-01

    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.

  6. Statistical analysis of honeybee survival after chronic exposure to insecticides.

    PubMed

    Dechaume Moncharmont, François-Xavier; Decourtye, Axel; Hennequet-Hantier, Christelle; Pons, Odile; Pham-Delègue, Minh-Hà

    2003-12-01

    Studies concerning long-term survival of honeybees raise the problem of the statistical analysis of mortality data. In the present study, we used a modeling approach of survival data of caged bees under chronic exposure to two pesticides (imidacloprid and deltamethrin). Our model, based on a Cox proportional hazard model, is not restricted to a specific hazard functional form, such as in parametric approaches, but takes into account multiple covariates. We consider not only the pesticide treatment but also a nuisance variable (variability between replicates). Moreover, considering the occurrence of social interactions, the model integrates the fact that bees do not die independently of each other. We demonstrate the chronic toxicity induced by imidacloprid and deltamethrin. Our results also underline the role of the replicate effect, the density-dependent effect, and their interactions with the treatment effect. None of these parameters can be neglected in the assessment of chronic toxicity of pesticides to the honeybee.

  7. Chronic obstructive pulmonary disease and occupational exposure to silica.

    PubMed

    Rushton, Lesley

    2007-01-01

    Prolonged exposure to high levels of silica has long been known to cause silicosis This paper evaluates the evidence for an increased risk of chronic obstructive pulmonary disease (COPD) in occupations and industries in which exposure to crystalline silica is the primary exposure, with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests consistently elevated risks of developing COPD associated with silica exposure in several occupations, including the construction industry; tunneling; cement industry; brick manufacturing; pottery and ceramic work; silica sand, granite and diatomaceous earth industries; gold mining; and iron and steel founding, with risk estimates being high in some, even after taking into account the effect of confounders like smoking. Average dust levels vary from about 0.5 mg.m3 to over 10 mg.m3 and average silica levels from 0.04 to over 5 mg.m3, often well above occupational standards. Factors influencing the variation from industry to industry in risks associated with exposure to silica-containing dusts include (a) the presence of other minerals in the dust, particularly when associated with clay minerals; (b) the size of the particles and percentage of quartz; (c) the physicochemical characteristics, such as whether the dust is freshly fractured. Longitudinal studies suggest that loss of lung function occurs with exposure to silica dust at concentrations of between 0.1 and 0.2 mg.m3, and that the effect of cumulative silica dust exposure on airflow obstruction is independent of silicosis. Nevertheless, a disabling loss of lung function in the absence of silicosis would not occur until between 30 and 40 years exposure.

  8. Welding fume exposure and chronic obstructive pulmonary disease in welders.

    PubMed

    Koh, D-H; Kim, J-I; Kim, K-H; Yoo, S-W

    2015-01-01

    Occupational exposure is estimated to contribute 15% to the burden of chronic obstructive pulmonary disease (COPD). Welding fumes are suspected to accelerate the decline of lung function and development of COPD. To examine the relationship between welding fume exposure and COPD in Korean shipyard welders. The study involved a group of male welders working at two shipyards who underwent an annual health examination in 2010. Subjects completed a questionnaire about smoking habits and occupational history and a pulmonary function test (PFT) was carried out with strict quality control measures. Welding fume exposure concentrations were estimated using 884 measurements taken between 2002 and 2009 in one of the shipyards. Multiple linear and logistic regression was employed to evaluate the association between cumulative fume exposure and lung function parameters, controlling for age, height and cigarette smoking. Two hundred and forty subjects participated, with a mean age of 48 and mean work duration of 15 years. The mean cumulative fume exposure was 7.7mg/m(3). The prevalence of COPD was 15%. FEV1 and FVC showed non-significant negative correlations with cumulative fume exposure. Odds ratios of COPD were significantly elevated for the middle (3.9; 95% CI 1.4-13.3) and high exposure groups (3.8; 95% CI 1.03-16.2) compared with the low fume exposure group. Our findings support an association between welding fume exposure and increased risk of COPD. Further prospective study is needed to investigate whether this is a causal relationship. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Accidental exposure to polychlorinated biphenyls (PCB) in waste cargo after heavy seas. Global waste transport as a source of PCB exposure.

    PubMed

    Budnik, Lygia Therese; Wegner, Ralf; Rogall, Ulrich; Baur, Xaver

    2014-02-01

    After cargo with PCB-containing transformer oil waste was damaged in heavy seas, the vessel crew exposed to PCB developed itching and acne-form eruption of the skin. The objective of our study was to analyse this work-related incident and its effects on health. Air and wipe test samples were taken in the ship for analysis of PCB (28/52/101/138/153/180); clinical investigations of all seafarers (n = 6) included lung function, chest X-ray, clinical chemistry and biomonitoring (plasma PCBs, chlorophenols in urine) measured after a latency of 7 weeks. The biomonitoring data were adjusted according to age-related reference values and validated against controls (n = 96). Biomonitoring showed elevated PCB-28-/52/-102/-138 congeners (mean 1.16/0.91/136, ∑PCB: 5.82 μg/l), which correlates with the dust samples from the cargo hold (∑PCB. 9,440 mg/m(2)) and with 6.1 and 5.0 μg/m(3) in stern and bow cargo air samples. IgE elevation in two seafarers and substantial blood sedimentation rate increase with anaemia or pulmonary emphysema were unlikely to be caused by PCB exposure. Although two members showed slightly elevated airway resistance values, other lung function parameters were normal and reactive airways dysfunction syndrome due to PCBs could be excluded. Elevated chlorophenols in urine could contribute to the manifestation of chloracne. PCB-52/-101/-138 found in plasma and in air samples confirm exposure to PCB. Acne-form skin eruptions were from occupational exposure to polychlorinated biphenyls in the spilt transformer oil. There were no other abnormal findings in medical and clinical examinations that could be attributed to PCBs. This does not exclude possible long-term effects.

  10. Chronic exposure to ELF fields may induce depression

    SciTech Connect

    Wilson, B.W.

    1988-01-01

    Exposure to extremely-low-frequency (ELF) electric or magnetic fields has been postulated as a potentially contributing factor in depression. Epidemiologic studies have yielded positive correlations between magnetic- and/or electric-field strengths in local environments and the incidence of depression-related suicide. Chronic exposure to ELF electric or magnetic fields can disrupt normal circadian rhythms in rat pineal serotonin-N-acetyltransferase activity as well as in serotonin and melatonin concentrations. Such disruptions in the circadian rhythmicity of pineal melatonin secretion have been associated with certain depressive disorders in human beings. In the rat, ELF fields may interfere with tonic aspects of neuronal input to the pineal gland, giving rise to what may be termed functional pinealectomy. If long-term exposure to ELF fields causes pineal dysfunction in human beings as it does in the rat, such dysfunction may contribute to the onset of depression or may exacerbate existing depressive disorders. 85 references.

  11. Effects of Mild Chronic Intermittent Cold Exposure on Rat Organs

    PubMed Central

    Wang, Xiaohui; Che, Honglei; Zhang, Wenbin; Wang, Jiye; Ke, Tao; Cao, Rui; Meng, Shanshan; Li, Dan; Weiming, Ouyang; Chen, Jingyuan; Luo, Wenjing

    2015-01-01

    Cold adaptation is a body's protective response to cold stress. Mild chronic intermittent cold (CIC) exposure has been used to generate animal models for cold adaptation studies. However, the effects of mild CIC exposure on vital organs are not completely characterized. In the present study, we exposed rats to mild CIC for two weeks, and then measured the body weights, the weights of brown adipose tissue (BAT), the levels of ATP and reactive oxygen species (ROS) in the brains, livers, hearts, muscles and BATs. Rats formed cold adaptation after exposure to CIC for two weeks. Compared to rats of the control group that were hosted under ambient temperature, rats exposed to mild CIC showed a lower average body weight, but a higher weight of brown adipose tissue (BAT). Rats exposed to CIC for two weeks also exhibited higher levels of ATP and ROS in all examined organs as compared to those of the control group. In addition, we determined the expression levels of cold-inducible RNA binding protein (Cirbp) and thioredoxin (TRX) in rat tissues after 2 weeks of CIC exposure. Both Cirbp and TRX were increased, suggesting a role of these two proteins for establishment of cold adaptation. Together, this study reveals the effects of mild CIC exposure on vital organs of rats during CIC exposure. PMID:26327811

  12. Metabolic consequences of chronic intermittent mild stress exposure.

    PubMed

    Thompson, Abigail K; Fourman, Sarah; Packard, Amy E B; Egan, Ann E; Ryan, Karen K; Ulrich-Lai, Yvonne M

    2015-10-15

    Chronic stress in humans has divergent effects on food intake, with some individuals reporting increased vs. decreased food intake during stress. This divergence may depend in part on stress intensity, with higher-intensity stressors preferentially promoting anorexia. Consistent with this idea, rodents given a high-intensity chronic variable stress paradigm have robustly decreased food intake and body weight gain. However, the metabolic effects of a less intense chronic stress paradigm are not clear. Thus in the present study, adult male rats were given chronic intermittent mild stress (CIMS) exposure (3 cycles, in which each cycle consists of once daily mild stress for 5 days/week for 2 weeks, followed by 2 weeks of no stress) vs. non-stress controls, combined with ongoing access to a palatable diet (PD; choice of chow, high-fat diet, 30% sucrose drink, and water) vs. control diet (chow and water). As expected, access to PD increased caloric intake, body weight gain, and adiposity, and impaired glucose tolerance. CIMS decreased body weight gain only during the first cycle of stress and did not affect body weight gain thereafter, regardless of diet. Moreover, CIMS did not alter total food intake, adiposity or glucose tolerance regardless of diet. Lastly, CIMS transiently increased high-fat diet preference in PD-fed rats during the first stress cycle. Collectively, these results suggest that CIMS has relatively modest metabolic effects that occur primarily during initial stress exposure. These results support the hypothesis that the metabolic consequences of chronic stress vary with stress intensity and/or frequency.

  13. Chronic exposure to environmental levels of tribromophenol impairs zebrafish reproduction

    SciTech Connect

    Deng Jun; Liu Chunsheng; Yu Liqin; Zhou Bingsheng

    2010-02-15

    Tribromophenol (2,4,6-TBP) is ubiquitously found in aquatic environments and biota. In this study, we exposed zebrafish embryos (F{sub 0}; 2'''' days post-fertilization, dpf) to environmental concentration (0.3 mug/L) and a higher concentration (3.0 mug/L) of TBP and assessed the impact of chronic exposure (120 dpf) on reproduction. TBP exposure did not cause a significant increase in the malformation and reduction in the survival in the F{sub 0}-generation fish. After TBP exposure, the plasma testosterone and estradiol levels significantly increased in males and decreased in females. The transcription of steroidogenic genes (3beta-HSD, 17beta-HSD, CYP17, CYP19A, CYP19B) was significantly upregulated in the brain and testes in males and downregulated in the brain and ovary in females. TBP exposure significantly downregulated and upregulated the expression of VTG in the liver of female and male fish, respectively. Meanwhile, TBP exposure altered the sex ratio toward a male-dominant state. The F{sub 1}-generation larvae exhibited increased malformation, reduced survival, and retarded growth, suggesting that TBP in the aquatic environment has significant adverse effects on fish population.

  14. Estimation of Chronic Personal Exposure to Airborne Polycyclic Aromatic Hydrocarbons

    PubMed Central

    Choi, Hyunok; Zdeb, Michael; Perera, Frederica; Spengler, John

    2015-01-01

    Background Polycyclic aromatic hydrocarbons (PAH) exposure from solid fuel burning represents an important public health issue for the majority of the global population. Yet, understanding of individual-level exposures remains limited. Objectives To develop regionally adaptable chronic personal exposure model to pro-carcinogenic PAH (c-PAH) for the population in Kraków, Poland. Methods We checked the assumption of spatial uniformity in eight c-PAH using the coefficients of divergence (COD), a marker of absolute concentration differences. Upon successful validation, we developed personal exposure models for eight pro-carcinogenic PAH by integrating individual-level data with area-level meteorological or pollutant data. We checked the resulting model for accuracy and precision against home outdoor monitoring data. Results During winter, COD of 0.1 for Kraków suggest overall spatial uniformity in the ambient concentration of the eight c-PAH. The three models that we developed were associated with index of agreement approximately equal to 0.9, root mean square error < 2.6 ng/m3, and 90th percentile of absolute difference ≤ 4 ng/m3 for the predicted and the observed concentrations for eight pro-carcinogenic PAH. Conclusions Inexpensive and logistically feasible information could be used to estimate chronic personal exposure to PAH profiles, in lieu of costly and labor-intensive personal air monitoring at wide scale. At the same time, thorough validation through direct personal monitoring and assumption checking are critical for successful model development. PMID:25965038

  15. Chronic Ethanol Exposure: Pathogenesis of Pulmonary Disease and Dysfunction

    PubMed Central

    Traphagen, Nicole; Tian, Zhi; Allen-Gipson, Diane

    2015-01-01

    Ethanol (EtOH) is the world’s most commonly used drug, and has been widely recognized as a risk factor for developing lung disorders. Chronic EtOH exposure affects all of the organ systems in the body and increases the risk of developing pulmonary diseases such as acute lung injury and pneumonia, while exacerbating the symptoms and resulting in increased mortality in many other lung disorders. EtOH and its metabolites inhibit the immune response of alveolar macrophages (AMs), increase airway leakage, produce damaging reactive oxygen species (ROS), and disrupt the balance of antioxidants/oxidants within the lungs. In this article, we review the role of EtOH exposure in the pathogenesis and progression of pulmonary disease. PMID:26492278

  16. Chronic ethanol exposure during development: disturbances of breathing and adaptation.

    PubMed

    Dubois, C J; Kervern, M; Naassila, M; Pierrefiche, O

    2013-11-01

    The effects of prenatal exposure to some drugs of abuse, such as nicotine, on breathing function have been clearly established. However, the case of alcohol (ethanol), the most widely consume drug of abuse, remains unknown. Prenatal ethanol consumption in humans may lead to fetal alcohol syndrome and although the effect of chronic prenatal ethanol exposure (CPEE) on cognitive function is frequently studied, nothing is known about CPEE's effects on breathing as compared with other drugs of abuse. The role of nicotine for example, in human neonatal pathology, such as sudden infant death syndrome, is acknowledged today, whereas the full scope of CPEE's role is only recently emerging. Here, we review preclinical investigations on the effects of CPEE on breathing in different animal models, including possible mechanisms of adaptation to CPEE. These recent preclinical studies shed new light on a widely used drug of abuse and should facilitate the understanding of the danger posed by alcohol consumption during pregnancy.

  17. A chronic eosinophilic pneumonia case with long exposure to isocyanates.

    PubMed

    Yalcin, Funda; Sak, Zafer Hasan Ali; Boyaci, Nurefsan; Gencer, Mehmet

    2014-10-01

    Chronic eosinophilic pneumonia (CEP) is a disease with unknown etiology, characterized by peripheral blood eosinophilia and abnormal eosinophil accumulation in the lungs. A 43-year-old male with 30 years history of exposure to isocyanates was admitted with the complaint of sputum, cough, progressive dyspnoea, and weight loss. Physical examination revealed bilaterally decreased breath sounds and extensive rales. On laboratory analysis; leukocytosis (12.3 10(3)/proportional variant L), hypereosinophilia (30%), elevated CRP and RF (1000 IU/ml), and IgE levels (1160 IU/ml) in the serum were observed. Chest radiograph and computed tomography on admission showed reticulonodular pattern at both lung fields. Pulmonary function tests assumed a restrictive pattern and a low diffusing capacity. Bronchoalveolar lavage revealed a marked eosinophilia (50%). Transbronchial lung biopsy indicated eosinophilic pneumonia. In this case we aimed to describe a rare case of CEP probably caused by exposure to isocyanate.

  18. Responses of Hyalella azteca to acute and chronic microplastic exposures.

    PubMed

    Au, Sarah Y; Bruce, Terri F; Bridges, William C; Klaine, Stephen J

    2015-11-01

    Limited information is available on the presence of microplastics in freshwater systems, and even less is known about the toxicological implications of the exposure of aquatic organisms to plastic particles. The present study was conducted to evaluate the effects of microplastic ingestion on the freshwater amphipod, Hyalella azteca. Hyalella azteca was exposed to fluorescent polyethylene microplastic particles and polypropylene microplastic fibers in individual 250-mL chambers to determine 10-d mortality. In acute bioassays, polypropylene microplastic fibers were significantly more toxic than polyethylene microplastic particles; 10-d lethal concentration 50% values for polyethylene microplastic particles and polypropylene microplastic fibers were 4.64 × 10(4) microplastics/mL and 71.43 microplastics/mL, respectively. A 42-d chronic bioassay using polyethylene microplastic particles was conducted to quantify effects on reproduction, growth, and egestion. Chronic exposure to polyethylene microplastic particles significantly decreased growth and reproduction at the low and intermediate exposure concentrations. During acute exposures to polyethylene microplastic particles, the egestion times did not significantly differ from the egestion of normal food materials in the control; egestion times for polypropylene microplastic fibers were significantly slower than the egestion of food materials in the control. Amphipods exposed to polypropylene microplastic fibers also had significantly less growth. The greater toxicity of microplastic fibers than microplastic particles corresponded with longer residence times for the fibers in the gut. The difference in residence time might have affected the ability to process food, resulting in an energetic effect reflected in sublethal endpoints. © 2015 SETAC.

  19. Impacts of chronic sublethal exposure to clothianidin on winter honeybees.

    PubMed

    Alkassab, Abdulrahim T; Kirchner, Wolfgang H

    2016-07-01

    A wide application of systemic pesticides and detection of their residues in bee-collected pollen and nectar at sublethal concentrations led to the emergence of concerns about bees' chronic exposure and possible sublethal effects on insect pollinators. Therefore, special attention was given to reducing unintentional intoxications under field conditions. The sensitivity of winter bees throughout their long lifespan to residual exposure of pesticides is not well known, since most previous studies only looked at the effects on summer bees. Here, we performed various laboratory bioassays to assess the effects of clothianidin on the survival and behavior of winter bees. Oral lethal and sublethal doses were administered throughout 12-day. The obtained LD50 values at 48, 72, 96 h and 10 days were 26.9, 18.0, 15.1 and 9.5 ng/bee, respectively. Concentrations <20 µg/kg were found to be sublethal. Oral exposure to sublethal doses was carried out for 12-day and, the behavioral functions were tested on the respective 13th day. Although slight reductions in the responses at the concentrations 10 and 15 µg/kg were observed, all tested sublethal concentrations had showed non-significant effects on the sucrose responsiveness, habitation of the proboscis extension reflex and olfactory learning performance. Nevertheless, chronic exposure to 15 µg/kg affected the specificity of the early long-term memory (24 h). Since the tested concentrations were in the range of field-relevant concentrations, our results strongly suggest that related-effects on winter and summer bees' sensitivity should also be studied under realistic conditions.

  20. The Effect of Chronic Arsenic Exposure in Zebrafish

    PubMed Central

    Hallauer, Janell; Geng, Xiangrong; Yang, Hung-Chi; Shen, Jian; Tsai, Kan-Jen

    2016-01-01

    Abstract Arsenic is a prevalent environmental toxin and a Group one human carcinogenic agent. Chronic arsenic exposure has been associated with many human diseases. The aim of this study is to evaluate zebrafish as an animal model to assess arsenic toxicity in elevated long-term arsenic exposure. With prolonged exposure (6 months) to various concentrations of arsenic from 50 ppb to 300 ppb, effects of arsenic accumulation in zebrafish tissues, and phenotypes were investigated. Results showed that there are no significant changes of arsenic retention in zebrafish tissues, and zebrafish did not exhibit any visible tumor formation under arsenic exposure conditions. However, the zebrafish demonstrate a dysfunction in their neurological system, which is reflected by a reduction of locomotive activity. Moreover, elevated levels of the superoxide dismutase (SOD2) protein were detected in the eye and liver, suggesting increased oxidative stress. In addition, the progenies of arsenic-treated parents displayed a smaller biomass (four-fold reduction in body weight) compared with those from their parental controls. This result indicates that arsenic may induce genetic or epigenetic changes that are then passed on to the next generation. Overall, this study demonstrates that zebrafish is a convenient vertebrate model with advantages in the evaluation of arsenic-associated neurological disorders as well as its influences on the offspring. PMID:27140519

  1. Chronic bronchiolitis in nonhuman primates after prolonged ozone exposure

    SciTech Connect

    Eustis, S.L.; Schwartz, L.W.; Kosch, P.C.; Dungworth, D.L.

    1981-01-01

    Bonnet monkeys (Macaca radiata) were exposed to 0.0, 0.5, or 0.8 ppm ozone for 7, 28, or 90 consecutive days, 8 hours per day. The pulmonary response was evaluated by means of pulmonary function testing, light microscopy, scanning electron microscopy, transmission microscopy, autoradiography, and morphometry. Pulmonary function values obtained before exposure did not statistically differ from values obtained after exposure. A general trend of increased quasistatic compliance of the lung was observed in both groups of exposed monkeys. Morphologic changes were principally characterized as low-grade chronic respiratory bronchiolitis. Tritiated thymidine labeling and counts of respiratory bronchiolar epithelium demonstrated up to a 37-fold increase in labeling index at 7 days but only a sevenfold increase at 90 days. Differential cell counts demonstrated an increase in the proportion of cuboidal bronchiolar cells constituting the respiratory bronchiolar epithelium. In control monkeys, 60% of the epithelial cells were cuboidal bronchiolar cells. At 90 days of exposure, more than 90% of the respiratory bronchiolar cells were cuboidal in appearance. The cuboidal bronchiolar cell in control monkeys does not appear secretory, but membrane-bound electron-dense secretory granules are present in this cell type from exposed monkeys. Epithelial hyperplasia (increased number of cells per millimeter of airway length) persisted through 90 days of exposure at a level slightly above that present at 7 days.

  2. Chronic Alcohol Exposure Renders Epithelial Cells Vulnerable to Bacterial Infection

    PubMed Central

    Wood, Stephen; Pithadia, Ravi; Rehman, Tooba; Zhang, Lijuan; Plichta, Jennifer; Radek, Katherine A.; Forsyth, Christopher; Keshavarzian, Ali; Shafikhani, Sasha H.

    2013-01-01

    Despite two centuries of reports linking alcohol consumption with enhanced susceptibility to bacterial infections and in particular gut-derived bacteria, there have been no studies or model systems to assess the impact of long-term alcohol exposure on the ability of the epithelial barrier to withstand bacterial infection. It is well established that acute alcohol exposure leads to reduction in tight and adherens junctions, which in turn leads to increases in epithelial cellular permeability to bacterial products, leading to endotoxemia and a variety of deleterious effects in both rodents and human. We hypothesized that reduced fortification at junctional structures should also reduce the epithelial barrier’s capacity to maintain its integrity in the face of bacterial challenge thus rendering epithelial cells more vulnerable to infection. In this study, we established a cell-culture based model system for long-term alcohol exposure to assess the impact of chronic alcohol exposure on the ability of Caco-2 intestinal epithelial cells to withstand infection when facing pathogenic bacteria under the intact or wounded conditions. We report that daily treatment with 0.2% ethanol for two months rendered Caco-2 cells far more susceptible to wound damage and cytotoxicity caused by most but not all bacterial pathogens tested in our studies. Consistent with acute alcohol exposure, long-term ethanol exposure also adversely impacted tight junction structures, but in contrast, it did not affect the adherens junction. Finally, alcohol-treated cells partially regained their ability to withstand infection when ethanol treatment was ceased for two weeks, indicating that alcohol’s deleterious effects on cells may be reversible. PMID:23358457

  3. 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.

  4. Accidental Bowel Leakage

    MedlinePlus

    Member Login Join Pay Dues Follow us: Women's Health Care Physicians Contact Us My ACOG ACOG Departments Donate ... underwear or pads Diarrhea Constipation How will my health care provider diagnose the cause of my accidental bowel ...

  5. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice.

    PubMed

    Zhang, Jia-Qing; Gao, Bin-Wen; Wang, Jing; Wang, Xian-Wei; Ren, Qiao-Ling; Chen, Jun-Feng; Ma, Qiang; Xing, Bao-Song

    2016-01-01

    Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals.

  6. Alterations in splanchnic blood flow following chronic ethanol exposure.

    PubMed

    Piano, M R; Ferguson, J L; Melchior, C L

    1990-08-01

    The purpose of these experiments was to determine whether or not tolerance develops to the effect of 3.0 g/kg ethanol on total and regional splanchnic blood flow in male Wistar rats. The animals were given the Lieber-DeCarli liquid diet containing ethanol for 10 days; ethanol-fed animals were withdrawn 24 hr prior to experiments. Regional blood flow and cardiac output (CO) were measured by the reference microsphere technique after an intraperitoneal injection of 3.0 g/kg of ethanol. Acute ethanol administration produced early nonsustained increases in portal vein blood flow in animals fed ethanol for 10 days and withdrawn for 24 hr and in control animals. However, after chronic exposure to ethanol, the pattern of increase in blood flow in response to ethanol in the splanchnic organs was different between the ethanol-fed and control groups. Increases in portal vein flow in control groups were due to concomitant increases in small intestinal, colonic, and cecal blood flow while the increase in the ethanol-fed group was due to a rise in small intestinal and stomach blood flow. The increase in stomach blood flow that occurred in the animals treated chronically with ethanol may be viewed as a conditioned response to ethanol, since this was not found in the control group. These results, demonstrate that the pattern of increase in blood flow in the splanchnic organs produced by an acute dose of ethanol depends on the animal's previous exposure to ethanol.

  7. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice

    PubMed Central

    Zhang, Jia-Qing; Gao, Bin-Wen; Wang, Jing; Wang, Xian-Wei; Ren, Qiao-Ling; Chen, Jun-Feng; Ma, Qiang; Xing, Bao-song

    2016-01-01

    Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals. PMID:26785375

  8. Biology Based Lung Cancer Model for Chronic Low Radon Exposures

    SciTech Connect

    Truta-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

    2008-08-07

    Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival.To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

  9. Biology Based Lung Cancer Model for Chronic Low Radon Exposures

    NASA Astrophysics Data System (ADS)

    TruÅ£ǎ-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

    2008-08-01

    Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival. To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

  10. Violence exposure, a chronic psychosocial stressor, and childhood lung function

    PubMed Central

    Suglia, Shakira Franco; Ryan, Louise; Laden, Francine; Dockery, Douglas; Wright, Rosalind J

    2011-01-01

    Background Chronic psychosocial stressors, including violence, have been linked to neuropsychological and behavioral development in children as well as physiologic alterations that may lead to broader health effects. Methods We examined the relationship between violence and childhood lung function in a prospective birth cohort of 313 urban children 6 and 7 years of age. Mothers reported on their child’s lifetime exposure to community violence (ETV) and interparental conflict in the home [Conflict Tactics Scale (CTS)] within one year of the lung function assessment. Results In linear regression analyses, adjusting for maternal education, child’s age, race, birthweight, tobacco smoke exposure, and medical history, girls in the highest CTS verbal aggression tertile had a 5.5% (95% CI: −9.6, −1.5) decrease in percent predicted FEV1 and a 5.4% (95% CI: −9.7, −1.1) decrease in FVC compared to girls in the lowest tertile. The CTS verbal aggression subscale was associated with lung function among boys in the same direction, albeit this was not statistically significant. Boys in the highest ETV tertile had a 3.4% (95% CI: −8.0, 1.1) lower FEV1 and 5.3% lower (95% CI: −10.2, −0.4) FVC compared to boys in the lowest tertile. The ETV score was not a significant predictor of girl’s lung function. Conclusions Interparental conflict, specifically verbal aggression, and exposure to community violence were associated with decreased childhood lung function independent of socioeconomic status, tobacco smoke exposure, birthweight and respiratory illness history. Gender differences were noted based on the type of violence exposure which may warrant further exploration. PMID:18158365

  11. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  12. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  13. 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

  14. Acute exposure to UVB has a more profound effect on plant genome stability than chronic exposure.

    PubMed

    Boyko, Alex; Greer, Michael; Kovalchuk, Igor

    2006-12-01

    Environmental factors that damage DNA have various lengths of exposure and intensity levels. Although the results of increasing the intensity of a DNA damaging agent is often predictable, it is not clear whether the stage during development when the exposure is received has any influence on the amount of DNA damage. In this paper we analyzed the influence of UVB on the stability of Arabidopsis thaliana and the Nicotiana tabacum genomes. Our experiments showed that the acute exposure to UVB produces a significantly greater increase in homologous recombination frequency (HRF) and recombination rate (RR) compared with that produced by chronic exposure. The increase in HRF showed a positive correlation with UVB dose and a negative correlation with plant age. In other words, as the UVB dose was increased, there was a concomitant increase in HRF. Conversely, older plants had a lower HRF increase as compared to younger plants. Our experiments suggest that exposure to UVB makes the most significant impact on genome stability during the early stages of plant development.

  15. CHRONIC PERCHLORATE EXPOSURE CAUSES MORPHOLOGICAL ABNORMALITIES IN DEVELOPING STICKLEBACK

    PubMed Central

    Bernhardt, Richard R.; Von Hippel, Frank A.; O’Hara, Todd M.

    2011-01-01

    Few studies have examined the effects of chronic perchlorate exposure during growth and development, and fewer still have analyzed the effects of perchlorate over multiple generations. We describe morphological and developmental characteristics for threespine stickleback (Gasterosteus aculeatus) that were spawned and raised to sexual maturity in perchlorate-treated water (G1,2003) and for their offspring (G2,2004) that were not directly treated with perchlorate. The G1,2003 displayed a variety of abnormalities, including impaired formation of calcified traits, slower growth rates, aberrant sexual development, poor survivorship, and reduced pigmentation that allowed internal organs to be visible. Yet these conditions were absent when the offspring of contaminated fish (G2,2004) were raised in untreated water, suggesting a lack of transgenerational effects and that surviving populations may be able to recover following remediation of perchlorate-contaminated sites PMID:21465539

  16. Chronic Kidney Disease and Exposure to Nephrotoxic Metals

    PubMed Central

    Orr, Sarah E.; Bridges, Christy C.

    2017-01-01

    Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of functional nephrons. As injured nephrons become sclerotic and die, the remaining healthy nephrons undergo numerous structural, molecular, and functional changes in an attempt to compensate for the loss of diseased nephrons. These compensatory changes enable the kidney to maintain fluid and solute homeostasis until approximately 75% of nephrons are lost. As CKD continues to progress, glomerular filtration rate decreases, and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may enhance mortality and/or morbidity of an individual. Environmental toxicants of particular concern are arsenic, cadmium, lead, and mercury. Since these metals are present throughout the environment and exposure to one or more of these metals is unavoidable, it is important that the way in which these metals are handled by target organs in normal and disease states is understood completely. PMID:28498320

  17. Chronic cyanide exposure: a clinical, radioisotope, and laboratory study.

    PubMed Central

    El Ghawabi, S H; Gaafar, M A; El-Saharti, A A; Ahmed, S H; Malash, K K; Fares, R

    1975-01-01

    The effect of chronic cyanide exposure in the electroplating sections of three factories employing 36 workers was studied and compared with a control group. The concentration of cyanides to which the workers were exposed was measured. The regression line showing the relationship between thiocyanates in urine and the concentration of cyanides in the air was plotted. Increased percentages of haemoglobin and lymphocyte count were present in all exposed workers, in addition to punctate basophilia in 28 workers. Cyanmethaemoglobin was found to be characteristic. Apart from other complaints, two men with psychosis similar to one case reported in therapeutic thiocyanate intoxication were found. Twenty of the workers had thyroid enlargements to a variable degree and consistency, in two of whom it resembled lymphadenoid goitre. Thyroid 131I uptakes at 4 and 24 hours were significantly higher than in the controls, while 131PBI was unchanged. The reason for this iodine deficiency-like action is discussed. PMID:1156569

  18. Hepatitis caused by occupational chronic exposure to trichloroethylene.

    PubMed

    Anagnostopoulos, G; Sakorafas, G H; Grigoriadis, K; Margantinis, G; Kostopoulos, P; Tsiakos, S; Arvanitidis, D

    2004-01-01

    Trichloroethylene (TCE) is an organic solvent used in a variety of industries for more than 60 years. Several adverse events following acute or chronic exposure to trichloroethylene have been reported. However, TCE-induced hepatitis is very rare. We present the case of a 55-year old male who was presented with anorexia, fatigue and upper abdominal discomfort. Routine laboratory examination revealed marked elevation of liver enzyme values. All possible causes of hepatitis were ruled out. The patient has been working as a shoemaker, in a small room of a basement, with insufficient air-exchange; during the last 5 years he used daily a glue containing 1,1,1 trichloroethylene. The diagnosis of hepatitis was confirmed by liver biopsy. The offending agent was withdrawn. Three months later, he was "feeling well" and liver enzyme values had returned to normal. Six months after the initial biopsy, a second liver biopsy was performed and histology was markedly improved. Workers exposed to hazardous chemicals, such as trichloroethylene, must have periodic follow-up examinations. Good work practices are very important when using toxic substances. In patients whose initial diagnostic workout is negative for common causes of acute or chronic hepatitis, toxic causes should be considered, with emphasis on patient's job and working conditions.

  19. Memory Deficit Recovery after Chronic Vanadium Exposure in Mice.

    PubMed

    Folarin, Oluwabusayo; Olopade, Funmilayo; Onwuka, Silas; Olopade, James

    2016-01-01

    Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

  20. Safety assessment of chronic oral exposure to iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Chamorro, Susana; Gutiérrez, Lucía; Vaquero, María Pilar; Verdoy, Dolores; Salas, Gorka; Luengo, Yurena; Brenes, Agustín; José Teran, Francisco

    2015-05-01

    Iron oxide nanoparticles with engineered physical and biochemical properties are finding a rapidly increasing number of biomedical applications. However, a wide variety of safety concerns, especially those related to oral exposure, still need to be addressed for iron oxide nanoparticles in order to reach clinical practice. Here, we report on the effects of chronic oral exposure to low doses of γ-Fe2O3 nanoparticles in growing chickens. Animal observation, weight, and diet intake reveal no adverse signs, symptoms, or mortality. No nanoparticle accumulation was observed in liver, spleen, and duodenum, with feces as the main excretion route. Liver iron level and duodenal villi morphology reflect the bioavailability of the iron released from the partial transformation of γ-Fe2O3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe2O3 nanoparticles indicate the enhancement of a ferric over ferrous pathway supporting the role of mucins. Our findings reveal that oral administration of iron oxide nanoparticles is a safe route for drug delivery at low nanoparticle doses.

  1. Safety assessment of chronic oral exposure to iron oxide nanoparticles.

    PubMed

    Chamorro, Susana; Gutiérrez, Lucía; Vaquero, María Pilar; Verdoy, Dolores; Salas, Gorka; Luengo, Yurena; Brenes, Agustín; José Teran, Francisco

    2015-05-22

    Iron oxide nanoparticles with engineered physical and biochemical properties are finding a rapidly increasing number of biomedical applications. However, a wide variety of safety concerns, especially those related to oral exposure, still need to be addressed for iron oxide nanoparticles in order to reach clinical practice. Here, we report on the effects of chronic oral exposure to low doses of γ-Fe2O3 nanoparticles in growing chickens. Animal observation, weight, and diet intake reveal no adverse signs, symptoms, or mortality. No nanoparticle accumulation was observed in liver, spleen, and duodenum, with feces as the main excretion route. Liver iron level and duodenal villi morphology reflect the bioavailability of the iron released from the partial transformation of γ-Fe2O3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe2O3 nanoparticles indicate the enhancement of a ferric over ferrous pathway supporting the role of mucins. Our findings reveal that oral administration of iron oxide nanoparticles is a safe route for drug delivery at low nanoparticle doses.

  2. Prepubertal gynecomastia and chronic lavender exposure: report of three cases.

    PubMed

    Diaz, Alejandro; Luque, Laura; Badar, Zain; Kornic, Steve; Danon, Marco

    2016-01-01

    Prepubertal gynecomastia is a rare condition characterized by the growth of breast tissue in males as a consequence of early exposure to sexual hormones. When this condition is present, pathological sources of testosterone/estrogen production, such as adrenal or gonadal tumors must be searched for. A few reports have described an association between gynecomastia and substances that produce stimulation of the estrogen receptor, such as lavender and tea tree oil. Here we describe the cases of three boys who presented with prepubertal gynecomastia and were chronically exposed to lavender. Two of these boys were exposed to a cologne, named agua de violetas, used by Hispanic communities in the US, and in their countries of origin. We studied a sample of the cologne used by one of the patients. Analysis of the chemical composition of the agua de violetas cologne was performed using high-performance liquid chromatography as well as off-line mass spectrometric detection. All these, combined with the physical appearance and the smell, determined that the cologne had lavender as an ingredient. Exposure to estrogenic substances, such as lavender, should be explored in children presenting with prepubertal gynecomastia/thelarche.

  3. Composite accidental axions

    NASA Astrophysics Data System (ADS)

    Redi, Michele; Sato, Ryosuke

    2016-05-01

    We present several models where the QCD axion arises accidentally. Confining gauge theories can generate axion candidates whose properties are uniquely determined by the quantum numbers of the new fermions under the Standard Model. The Peccei-Quinn symmetry can emerge accidentally if the gauge theory is chiral. We generalise previous constructions in a unified framework. In some cases these models can be understood as the deconstruction of 5-dimensional gauge theories where the Peccei-Quinn symmetry is protected by locality but more general constructions are possible.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Accidental carbon monoxide poisoning.

    PubMed

    Zeller, W P; Miele, A; Suarez, C; Hannigan, J; Hurley, R M

    1984-12-01

    In this case report of an accidental automobile carbon monoxide poisoning, we identify the following risk factors: freezing temperature, young passenger age, location in the rear of the auto, smaller patient mass, and auto disrepair. The pathogenesis of carbon monoxide poisoning is reviewed. Emergency treatment and suggested criteria for hyperbaric oxygen use in pediatric patients are discussed.

  10. 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...

  11. 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...

  12. Impact of chronic lead exposure on selected biological markers.

    PubMed

    Jangid, Ambica P; John, P J; Yadav, D; Mishra, Sandhya; Sharma, Praveen

    2012-01-01

    Lead poisoning remains a major problem in India due to the lack of awareness of its ill effects among the clinical community. Blood lead, δ-aminolevulinic acid dehydratase (δ-ALAD) and zinc protoporphyrin (ZPP) concentrations are widely used as biomarkers for lead toxicity The present study was designed to determine the impact of chronic lead exposure on selected biological markers. A total of 250 subjects, of both sexes, ranging in age from 20 to 70 years, were recruited. On the basis of BLLs, the subjects were categorized into four groups: Group A (BLL: 0-10 μg/dl), Group B (BLL: 10-20 μg/dl). Group C (BLL: 20-30 μg/dl) and Group D (BLL: 30-40 μg/dl) having BLLs of 3.60 ± 2.71 μg/dl, 15.21 ± 2.65 μg/dl, 26.82 ± 2.53 μg/dl and 36.38 ± 2.83 μg/dl, respectively. Significant changes in biological markers due to elevated BLLs were noted. The relation of BLL and biological markers to demographic characteristics such as sex, habits, diet and substances abuse (smoking effect) were also studied in the present investigation. Males, urban population, non-vegetarians, and smokers had higher blood lead levels. δ-ALAD activity was found to be significantly lower with increased BLL (P < 0.001), while the ZPP level was significantly higher with increased BLL (P < 0.001). Further, BLL showed a negative correlation with δ-ALAD (r = -0.425, P < 0.001, N = 250) and a positive correlations with ZPP (r = 0.669, P < 0.001, N = 250). Chronic lead exposure affects the prooxidant-antioxidant equilibrium leading to cellular oxidative stress.

  13. Vitamin D and UV exposure in chronic kidney disease

    PubMed Central

    Krause, Rolfdieter

    2013-01-01

    With loss of renal function and decreasing glomerula filtration rate the serum levels of 25-hydroxyvitamin D [25(OH)D] as well as 1,25-dihydroxyvitamin D [1,25 (OH)2 D] often decrease simultaneously. In representative groups of German patients on renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) our group retrospectively analyzed the vitamin D status over a period of 12 y (1995‒2006). Only 11% of patients had a serum level of 25(OH)D that was > 30 ng/ml, more than 70% had a level of 25(OH)D < 20 ng/ml. In clinical trials we used sun-simulating artificial lamps to produce vitamin D3 in the skin. Partial-body irradiation (15% of body surface) was used during the routine hemodialysis treatment. Whole-body UV exposure was done in a standing position three times a week before the hemodialysis treatment. With both procedures we observed an increase of the serum level of 25(OH)2D3 by approx. 35–50% over a period of 2‒3 mo, maintenance of trabecular bone mineral density and a normalization of systolic and diastolic blood pressure. Heart rate variability improved during the whole-body radiation intervention period by 20‒25%. Patients who continued the whole-body irradiation regularly two or three times before starting the routine hemodialysis session had maintained normal levels of circulating 25(OH)D3 and of 1,25(OH)2D3. Therefore, from our data it can be recommended that intermittent suberythemal UVB exposure with a sun-simulation spectrum is effective to treat and/or protect against vitamin D deficiency in chronic and end-stage kidney disease patients. PMID:24494043

  14. Vitamin D and UV exposure in chronic kidney disease.

    PubMed

    Krause, Rolfdieter

    2013-01-01

    With loss of renal function and decreasing glomerula filtration rate the serum levels of 25-hydroxyvitamin D [25(OH)D] as well as 1,25-dihydroxyvitamin D [1,25 (OH)2 D] often decrease simultaneously. In representative groups of German patients on renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) our group retrospectively analyzed the vitamin D status over a period of 12 y (1995‒2006). Only 11% of patients had a serum level of 25(OH)D that was > 30 ng/ml, more than 70% had a level of 25(OH)D < 20 ng/ml. In clinical trials we used sun-simulating artificial lamps to produce vitamin D3 in the skin. Partial-body irradiation (15% of body surface) was used during the routine hemodialysis treatment. Whole-body UV exposure was done in a standing position three times a week before the hemodialysis treatment. With both procedures we observed an increase of the serum level of 25(OH)2D3 by approx. 35-50% over a period of 2‒3 mo, maintenance of trabecular bone mineral density and a normalization of systolic and diastolic blood pressure. Heart rate variability improved during the whole-body radiation intervention period by 20‒25%. Patients who continued the whole-body irradiation regularly two or three times before starting the routine hemodialysis session had maintained normal levels of circulating 25(OH)D3 and of 1,25(OH)2D3. Therefore, from our data it can be recommended that intermittent suberythemal UVB exposure with a sun-simulation spectrum is effective to treat and/or protect against vitamin D deficiency in chronic and end-stage kidney disease patients.

  15. Chronic fluoxetine ameliorates adolescent chronic nicotine exposure-induced long-term adult deficits in trace conditioning.

    PubMed

    Connor, David A; Gould, Thomas J

    2017-10-01

    Development of the brain, including the prefrontal cortex and hippocampus, continues through adolescence. Chronic nicotine exposure during adolescence may contribute to long-term deficits in forebrain-dependent learning. It is unclear if these deficits emerge immediately after exposure and if they can be ameliorated. In this study, C57BL/6J mice were treated with chronic nicotine (6.3 or 12.6 mg/kg/day) over 12 days beginning at adolescence, postnatal day (PND) 38, or adulthood, PND 56-63 ± 3. We investigated the effects of short-term (24 h) abstinence on trace fear conditioning and found that adult treatment resulted in deficits (6.3 and 12.6 mg/kg/day), but adolescent chronic nicotine treatment had no effect. In contrast, adolescent treatment with chronic nicotine (12.6 mg/kg/day) elicited a long-term (30 days) learning deficit, but adult chronic nicotine treatment did not. Using the elevated plus maze (EPM) we found no long-term changes in anxiety-related behavior after chronic nicotine exposure at either time-point. We investigated if chronic fluoxetine (FLX) could ameliorate adolescent chronic nicotine-associated long-term deficits in trace conditioning. We found that chronic FLX (160 mg/L) in drinking water ameliorated the long-term deficit in trace fear conditioning associated with nicotine exposure during adolescence. Additionally, in the same animals, we examined changes in total BDNF protein in the dorsal hippocampus (DH), ventral hippocampus (VH), and prefrontal cortex (PFC). Chronic FLX increased DH BDNF. Our data indicate nicotine administration during adolescence leads to late onset, long-lasting deficits in hippocampus-dependent learning that chronic FLX treatment ameliorate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Acute and chronic poisoning from residential exposures to elemental mercury--Michigan, 1989-1990

    SciTech Connect

    Not Available

    1991-06-14

    From May 1989 through November 1990, eight episodes of elemental mercury exposure in private residences or schools in the United States were reported to the Agency for Toxic Substances and Disease Registry (ATSDR). The case studies in this report document two of these episodes (both in Michigan) of residential mercury poisoning--one involving acute mercury exposure, and the other, chronic exposure to elemental mercury. These episodes illustrate the differing clinical and toxicologic manifestations of acute and chronic mercury poisoning.

  17. Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure

    PubMed Central

    Buczynski, Matthew W.; Herman, Melissa A.; Natividad, Luis A.; Irimia, Cristina; Polis, Ilham Y.; Pugh, Holly; Chang, Jae Won; Niphakis, Micah J.; Cravatt, Benjamin F.; Roberto, Marisa; Parsons, Loren H.

    2016-01-01

    Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). The potency and selectivity of these inhibitors were established in rats in vitro (rat brain proteome), ex vivo (brain slices), and in vivo (intracerebroventricular administration) using activity-based protein profiling and targeted metabolomics analyses. Inhibition of DAGL (2-AG biosynthesis) rescues nicotine-induced VTA GABA signaling following CNE. Conversely, enhancement of 2-AG signaling in naïve rats by inhibiting 2-AG degradation recapitulates the loss of nicotine-induced GABA signaling evident following CNE. DAGL inhibition reduces nicotine self-administration without disrupting operant responding for a nondrug reinforcer or motor activity. Collectively, these findings provide a detailed characterization of selective inhibitors of rat brain DAGL and demonstrate that excessive 2-AG signaling contributes to a loss of inhibitory GABAergic constraint of VTA excitability following CNE. PMID:26755579

  18. Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure.

    PubMed

    Buczynski, Matthew W; Herman, Melissa A; Hsu, Ku-Lung; Natividad, Luis A; Irimia, Cristina; Polis, Ilham Y; Pugh, Holly; Chang, Jae Won; Niphakis, Micah J; Cravatt, Benjamin F; Roberto, Marisa; Parsons, Loren H

    2016-01-26

    Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). The potency and selectivity of these inhibitors were established in rats in vitro (rat brain proteome), ex vivo (brain slices), and in vivo (intracerebroventricular administration) using activity-based protein profiling and targeted metabolomics analyses. Inhibition of DAGL (2-AG biosynthesis) rescues nicotine-induced VTA GABA signaling following CNE. Conversely, enhancement of 2-AG signaling in naïve rats by inhibiting 2-AG degradation recapitulates the loss of nicotine-induced GABA signaling evident following CNE. DAGL inhibition reduces nicotine self-administration without disrupting operant responding for a nondrug reinforcer or motor activity. Collectively, these findings provide a detailed characterization of selective inhibitors of rat brain DAGL and demonstrate that excessive 2-AG signaling contributes to a loss of inhibitory GABAergic constraint of VTA excitability following CNE.

  19. Chronic caffeine exposure potentiates nicotine self-administration in rats.

    PubMed

    Shoaib, M; Swanner, L S; Yasar, S; Goldberg, S R

    1999-03-01

    The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the euphoric effects of nicotine. The aim of the present experiment was to examine effects of chronic exposure to caffeine on responding maintained by nicotine. Sprague-Dawley rats consuming caffeine (approximately 150-180 mg/kg per day) in their drinking water for 7 days prior to the beginning and throughout behavioural testing acquired intravenous nicotine self-administration (0.03 mg/kg per infusion) more rapidly than did controls. In a cross-over design, exclusion of caffeine brought levels of nicotine self-administration back to baseline, while adding caffeine to the drinking water of control rats increased responding maintained by nicotine over 90%. These findings strongly suggest that caffeine can potentiate the reinforcing properties of nicotine, thus highlighting the importance of environmental factors in shaping and maintaining tobacco smoking.

  20. 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...

  1. 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...

  2. 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.

  3. Accidental decapitation: a case report.

    PubMed

    Demirci, Serafettin; Dogan, Kamil Hakan; Erkol, Zerrin; Gunaydin, Gursel

    2009-09-01

    We report a case of an accidental decapitation of an agriculture worker in a field. The scene investigation revealed that the worker had loosely tied a scarf tied over his face in an attempt to diminish his exposure to barley dust, to which he was allergic, while distributing the barley loads with a shovel upon a trailer. The trailer was simultaneously being loaded by a helix elevator machine and its rotating shaft suddenly caught the victim's scarf and pulled it down to the victim's neck. The rotating motion immediately tightened the scarf around the neck resulting in hanging/strangulation noose that, by continued tightening, caused decapitation of the victim. The victim's body was found on the ground by the trailer and the victim's head was discovered in the barley load in the trailer. Examination revealed that the neck was severed at the level of the second and third cervical vertebrae.

  4. Testicular steroidogenesis is not altered by 137 cesium Chernobyl fallout, following in utero or post-natal chronic exposure.

    PubMed

    Grignard, Elise; Guéguen, Yann; Grison, Stéphane; Dublineau, Isabelle; Gourmelon, Patrick; Souidi, Maâmar

    2010-05-01

    The testis is especially sensitive to pollutants, including radionuclides. Following the Chernobyl nuclear power plant accident, several of these radionuclides were emitted and spread in the environment. Subsequently, children presented some disruptions of the endocrine system. To determine whether these disruptions were due to 137 cesium ((137)Cs) exposure, the effects of chronic contamination with low doses of (137)Cs in utero or from birth on testicular steroidogenesis in rats were studied. Contamination was continued for 9 months. No modification was observed in circulating level of hormones (17beta-estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone) following in utero or post-natal contamination. Expression of several genes involved in testicular steroidogenesis was affected (cyp19a1, fxr, sf-1), without modification of protein expression or activity. Our results suggest that growing organisms may be affected at the molecular level by (137)Cs contamination at this post-accidental dose. Copyright 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  5. Radiative accidental matter

    NASA Astrophysics Data System (ADS)

    Sierra, D. Aristizabal; Simoes, C.; Wegman, D.

    2016-07-01

    Accidental matter models are scenarios where the beyond-the-standard model physics preserves all the standard model accidental and approximate symmetries up to a cutoff scale related with lepton number violation. We study such scenarios assuming that the new physics plays an active role in neutrino mass generation, and show that this unavoidably leads to radiatively induced neutrino masses. We systematically classify all possible models and determine their viability by studying electroweak precision data, big bang nucleosynthesis and electroweak perturbativity, finding that the latter places the most stringent constraints on the mass spectra. These results allow the identification of minimal radiative accidental matter models for which perturbativity is lost at high scales. We calculate radiative charged-lepton flavor violating processes in these setups, and show that μ → eγ has a rate well within MEG sensitivity provided the lepton-number violating scale is at or below 5×105 GeV, a value (naturally) assured by the radiative suppression mechanism. Sizeable τ → μγ branching fractions within SuperKEKB sensitivity are possible for lower lepton-number breaking scales. We thus point out that these scenarios can be tested not only in direct searches but also in lepton flavor-violating experiments.

  6. Sudden Gains in Prolonged Exposure and Sertraline for Chronic PTSD

    PubMed Central

    Jun, Janie J.; Zoellner, Lori A.; Feeny, Norah C.

    2014-01-01

    Background Sudden gains are significant, rapid improvements in symptoms, larger than typical between-session symptom reduction.[8] Sudden gains in a large sample of individuals with PTSD have not been studied, and only one study has looked at it in pharmacotherapy, but not in PTSD. In the present study, we examined the occurrence of sudden gains in psychotherapy, specifically prolonged exposure (PE), and pharmacotherapy, specifically sertraline, for chronic PTSD. Method Sudden gains in PTSD symptoms (PTSD Symptom Scale-Self-Report[23]) were assessed in 200 individuals with PTSD during 10 weeks of PE or sertraline. Results Individuals in both PE (42.2%) and sertraline (31%) exhibited sudden gains. Individuals in PE made more gains toward the end of treatment (7.2%) than sertraline (2%, OR = 3.82). However, individuals in sertraline made larger gains during early treatment (M = 18.35, SD = 8.15) than PE (M = 12.53, SD = 5.16, d = .85). Notably, those on sertraline were more likely to exhibit a reversal of sudden gains than those in PE (OR = .23). Pointing to clinical significance, the presence of a sudden gain was associated with better reduction in symptoms from pre- to post-treatment (β = -.49). Conclusions Individuals in both PE and sertraline experienced gains, though sertraline was associated with earlier large but reversible gains, and PE was associated with later gains. This differential pattern of discontinuous change highlights potential differential mechanism for these therapies and marks important transition points for further detailed analyses of change mechanisms. PMID:23633445

  7. Temperature modulates phototrophic periphyton response to chronic copper exposure.

    PubMed

    Lambert, Anne Sophie; Dabrin, Aymeric; Morin, Soizic; Gahou, Josiane; Foulquier, Arnaud; Coquery, Marina; Pesce, Stéphane

    2016-01-01

    Streams located in vineyard areas are highly prone to metal pollution. In a context of global change, aquatic systems are generally subjected to multi-stress conditions due to multiple chemical and/or physical pressures. Among various environmental factors that modulate the ecological effects of toxicants, special attention should be paid to climate change, which is driving an increase in extreme climate events such as sharp temperature rises. In lotic ecosystems, periphyton ensures key ecological functions such as primary production and nutrient cycling. However, although the effects of metals on microbial communities are relatively well known, there is scant data on possible interactions between temperature increase and metal pollution. Here we led a study to evaluate the influence of temperature on the response of phototrophic periphyton to copper (Cu) exposure. Winter communities, collected in a 8 °C river water, were subjected for six weeks to four thermal conditions in microcosms in presence or not of Cu (nominal concentration of 15 μg L(-1)). At the initial river temperature (8 °C), our results confirmed the chronic impact of Cu on periphyton, both in terms of structure (biomass, distribution of algal groups, diatomic composition) and function (photosynthetic efficiency). At higher temperatures (13, 18 and 23 °C), Cu effects were modulated. Indeed, temperature increase reduced Cu effects on algal biomass, algal class proportions, diatom assemblage composition and photosynthetic efficiency. This reduction of Cu effects on periphyton may be related to lower bioaccumulation of Cu and/or to selection of more Cu-tolerant species at higher temperatures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Chronic intermittent hypoxia exposure-induced atherosclerosis: a brief review.

    PubMed

    Song, Dongmei; Fang, Guoqiang; Greenberg, Harly; Liu, Shu Fang

    2015-12-01

    Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-κB p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis.

  9. [The advance of model of action in low-dose chronic benzene exposure induced hematotoxicity].

    PubMed

    Gao, Chen; Zhang, Zhengbao; Chen, Liping; Chen, Wen

    2015-09-01

    Benzene is classified as Group 1 carcinogen by IARC. It has been found that benzene induces hematotoxicity even in low dose exposure. The identification of key events during benzene induced hematotoxicty leads to adjustment of occupational exposure limits of benzene. In this review, we focus on the exposure, metabolism, target organs, key epigenetic changes, toxicty effects and end points of low-dose chronic benzene exposure induced hematotoxicity and finally discuss the perspectives on the future study of this area.

  10. Occupational airways diseases from chronic low-level exposures to irritants.

    PubMed

    Balmes, John R

    2002-12-01

    Short-term, high-level exposures to dusts, gases, mists, fumes, and smoke that are irritating to the respiratory tract are capable of inducing asthma, the so-called reactive airways dysfunction syndrome. Such exposures, however, do not occur frequently; chronic or recurrent exposures to lower levels of irritants are much more common. This article reviews the evidence that supports the concept that low-level exposures to respiratory tract irritants can contribute to the development of chronic obstructive pulmonary disease and asthma.

  11. 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…

  12. 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…

  13. Chronic cadmium exposure stimulates SDF-1 expression in an ERα dependent manner.

    PubMed

    Ponce, Esmeralda; Aquino, Natalie B; Louie, Maggie C

    2013-01-01

    Cadmium is an omnipotent environmental contaminant associated with the development of breast cancer. Studies suggest that cadmium functions as an endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and activating the receptor to promote cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure is unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand the effects of prolonged cadmium exposure. This study aims to investigate the effects of chronic cadmium exposure on breast cancer progression. A MCF7 breast cancer cell line chronically exposed to 10(-7) M CdCl2 serves as our model system. Data suggest that prolonged cadmium exposures result in the development of more aggressive cancer phenotypes - increased cell growth, migration and invasion. The results from this study show for the first time that chronic cadmium exposure stimulates the expression of SDF-1 by altering the molecular interactions between ERα, c-jun and c-fos. This study provides a mechanistic link between chronic cadmium exposure and ERα and demonstrates that prolonged, low-level cadmium exposure contributes to breast cancer progression.

  14. Chronic Cadmium Exposure Stimulates SDF-1 Expression in an ERα Dependent Manner

    PubMed Central

    Ponce, Esmeralda; Aquino, Natalie B.; Louie, Maggie C.

    2013-01-01

    Cadmium is an omnipotent environmental contaminant associated with the development of breast cancer. Studies suggest that cadmium functions as an endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and activating the receptor to promote cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure is unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand the effects of prolonged cadmium exposure. This study aims to investigate the effects of chronic cadmium exposure on breast cancer progression. A MCF7 breast cancer cell line chronically exposed to 10−7 M CdCl2 serves as our model system. Data suggest that prolonged cadmium exposures result in the development of more aggressive cancer phenotypes – increased cell growth, migration and invasion. The results from this study show for the first time that chronic cadmium exposure stimulates the expression of SDF-1 by altering the molecular interactions between ERα, c-jun and c-fos. This study provides a mechanistic link between chronic cadmium exposure and ERα and demonstrates that prolonged, low-level cadmium exposure contributes to breast cancer progression. PMID:24015267

  15. Chronic exposure to alcohol alters network activity and morphology of cultured hippocampal neurons.

    PubMed

    Korkotian, Eduard; Botalova, Alena; Odegova, Tatiana; Segal, Menahem

    2015-03-01

    The effects of chronic exposure to moderate concentrations of ethanol were studied in cultured hippocampal neurons. Network activity, assessed by imaging of [Ca(2+)]i variations, was markedly suppressed following 5 days of exposure to 0.25-1% ethanol. The reduced activity was sustained following extensive washout of ethanol, but the activity recovered by blockade of inhibition with bicuculline. This reduction of network activity was associated with a reduction in rates of mEPSCs, but not in a change in inhibitory synaptic activity. Chronic exposure to ethanol caused a significant reduction in the density of mature dendritic spines, without an effect on dendritic length or arborization. These results indicate that chronic exposure to ethanol causes a reduction in excitatory network drive in hippocampal neurons adding another dimension to the chronic effects of alcohol abuse.

  16. 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 ...

  17. 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 ...

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

    SciTech Connect

    Korn, R.J.; Dockery, D.W.; Speizer, F.E.; Ware, J.H.; Ferris, B.G. Jr.

    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 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 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.

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

    SciTech Connect

    Korn, R.J.; Dockery, D.W.; Speizer, F.E.; Ware, J.H.; Ferris, B.G.

    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 exposed 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.

  20. 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.

  1. A Novel Antibody-Based Biomarker for Chronic Algal Toxin Exposure and Sub-Acute Neurotoxicity

    PubMed Central

    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. PMID:22567140

  2. 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.

  3. Does Environmental Enrichment Exposure Prior to Injury Influence Biomarkers Associated with Chronic Stage TBI?

    DTIC Science & Technology

    2012-12-01

    prior to injury is associated with elevated levels of brain-derived neurotrophic factor ( BDNF ) and other protective biomolecules during the chronic...housed animals; however BDNF and other biomarker levels during the chronic stage of TBI were not significantly different. The data suggests that EE...exposure prior to TBI has neuroprotective tendencies during the chronic stage; however BDNF and other biomarkers associated with improved

  4. Performance of self-reported occupational exposure compared to a job exposure matrix approach in asthma and chronic rhinitis

    PubMed Central

    Quinlan, Patricia J.; Earnest, Gillian; Eisner, Mark D.; Yelin, Edward H.; Katz, Patricia P.; Balmes, John R.; Blanc, Paul D.

    2009-01-01

    Objectives Self-reported exposure to vapors, gas, dust, or fumes (VGDF) has been widely used as an occupational exposure metric in epidemiologic studies of chronic lung diseases. Our objective was to characterize the performance of VGDF for repeatability, systematic misclassification, and sensitivity and specificity against exposure likelihood by a job exposure matrix (JEM). Methods We analyzed data from two interviews, 24 months apart, among adults with asthma and chronic rhinitis. Using distinct job as the unit of analysis, we tested a single response item (exposure to VGDF) against assignment using a job exposure matrix (JEM). We further analyzed VGDF and JEM among a subset of 199 subjects who reported the same job at both interviews, using logistic regression analysis to test factors associated with VGDF inconsistency and discordance with JEM. Results For 436 distinct jobs held by 348 subjects studied, VGDF was reported for 193 (44%); moderate to high exposure likelihood by JEM was assigned to 120 (28%). The sensitivity and specificity of VGDF against JEM was 71% and 66%, respectively. Among 199 subjects with the same job at both interviews, 32% had discordant VGDF status (kappa= 0.35). Those with chronic rhinitis without concomitant asthma compared to asthma alone were more likely to have a VGDF report that was discordant with the JEM (OR 3.6 [95% CI 1.4–9.0]; p=0.01). Rhinitis was also associated with reported VGDF in a job classified by JEM as low exposure (OR 3.9 [95% CI 1.6–9.4]; p=0.003). Conclusion The VGDF item is moderately sensitive measured against JEM as a benchmark. The measure is a useful assessment method for epidemiological studies of occupational exposure risk. PMID:18805880

  5. Chronic Lung Function Decline in Cotton Textile Workers: Roles of Historical and Recent Exposures to Endotoxin

    PubMed Central

    Shi, Jing; Mehta, Amar J.; Hang, Jing-qing; Zhang, Hongxi; Dai, Helian; Su, Li; Eisen, Ellen A.; Christiani, David C.

    2010-01-01

    Background Long-term occupational exposure to cotton dust that contains endotoxin is associated with chronic respiratory symptoms and excessive decline in forced expiratory volume in 1 sec (FEV1), but the mechanisms of endotoxin-related chronic airflow obstruction remain unclear. Objective In the current study, we examined temporal aspects of the exposure–response relationship between airborne endotoxin exposure, longitudinal change in FEV1, and respiratory symptoms in a cohort of Chinese cotton textile workers. Methods This prospective cohort study followed 447 cotton textile workers from 1981 to 2006.at approximately 5-year intervals. We used a generalized estimating equations approach to model FEV1 level and respiratory symptoms as a function of past exposure (cumulative exposure up to the start of the most recent 5-year survey interval) and cumulative exposure (within the most recent interval) to endotoxins, after adjusting for other covariates. Models were stratified by active versus retired work status and by years employed before the baseline survey (< 5 and ≥ 5 years). Results and conclusions Past exposure to endotoxin was associated with reduced FEV1 level among retired cotton workers. Among all cotton workers, past exposure was more strongly associated with reduced FEV1 for those hired < 5 years before baseline than for those who were hired ≥ 5 years after baseline. Recent endotoxin exposure was significantly associated with byssinosis, chronic bronchitis, and chronic cough. PMID:20797932

  6. 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…

  7. [Clinical and experimental studies of metabolic response to chronic exposure to coal dust].

    PubMed

    Fomenko, D V; Gorokhova, L G; Panev, N I; Kazitskaia, A S; Bondarev, O I

    2011-01-01

    In miners anthracosilicosis is caused by chronic exposure to coal dust and is characterized by progressive development of the inflammatory process, the expressed disorders of lipid metabolism, and immunodeficiency. In the experiment we revealed the stages of anthracosilicosis development according to which adequate measures of prevention and correction of the disorders caused by long exposure of an organism to coal dust are recommended.

  8. [Survey on accidental exposure to biological materials in the Hospital-University Complex of Sassari during the period 1995-2000].

    PubMed

    Masia, M D; Castiglia, P; Busonera, B; Valca, D; Maida, I; Mura, I

    2004-01-01

    To study professional exposure to biological materials an investigation was carried out in the Hospital-University Complex of Sassari during the period January 1st 1995-December 31 2000. 1003 occupational accidents were notified (incidence rate=6%). Infirmaries were the most at risk category (45%) and about the half part of the accidents occurred in surgical area (44.7%). The most frequent accident was needle puncture (53%); exposure involved principally the hands (76.3%). The basal serology of injured personnel showed low positivity for any HBV markers (72.7%), HCV (0.4%) and no positivity for HIV; while high levels were found among source patients. From the comparison between serological data (injured vs source), when ascertainable, emerged a biological hazard of 7.7% for HBV, 30.2% for HCV and 3.2% for HIV; however no seroconversions were observed at follow up. The study also pointed out the need of improve prevention programmes.

  9. Performance of self-reported occupational exposure compared to a job-exposure matrix approach in asthma and chronic rhinitis.

    PubMed

    Quinlan, P J; Earnest, G; Eisner, M D; Yelin, E H; Katz, P P; Balmes, J R; Blanc, P D

    2009-03-01

    Self-reported exposure to vapours, gas, dust or fumes (VGDF) has been widely used as an occupational exposure metric in epidemiological studies of chronic lung diseases. Our objective was to characterise the performance of VGDF for repeatability, systematic misclassification, and sensitivity and specificity against exposure likelihood by a job-exposure matrix (JEM). We analysed data from two interviews, 24 months apart, of adults with asthma and chronic rhinitis. Using distinct job as the unit of analysis, we tested a single response item (exposure to VGDF) against assignment using a JEM. We further analysed VGDF and the JEM among a subset of 199 subjects who reported the same job at both interviews, using logistic regression analysis to test factors associated with VGDF inconsistency and discordance with the JEM. VGDF was reported for 193 (44%) of 436 distinct jobs held by the 348 subjects studied; moderate to high exposure likelihood by JEM was assigned to 120 jobs (28%). The sensitivity and specificity of VGDF against JEM were 71% and 66%, respectively. Among 199 subjects with the same job at both interviews, 32% had a discordant VGDF status (kappa = 0.35). Those with chronic rhinitis without concomitant asthma compared to asthma alone were more likely to have a VGDF report discordant with the JEM (OR 3.6, 95% CI 1.4 to 9.0; p = 0.01). Rhinitis was also associated with reported VGDF in a job classified by the JEM as low exposure (OR 3.9, 95% CI 1.6 to 9.4; p = 0.003). The VGDF item is moderately sensitive measured against JEM as a benchmark. The measure is a useful assessment method for epidemiological studies of occupational exposure risk.

  10. Reactivation of thalamocortical plasticity by dark exposure during recovery from chronic monocular deprivation

    PubMed Central

    Montey, Karen L.; Quinlan, Elizabeth M.

    2015-01-01

    Chronic monocular deprivation induces severe amblyopia that is resistant to spontaneous reversal in adulthood. However, dark exposure initiated in adulthood reactivates synaptic plasticity in the visual cortex and promotes recovery from chronic monocular deprivation. Here we show that chronic monocular deprivation significantly decreases the strength of feedforward excitation and significantly decreases the density of dendritic spines throughout the deprived binocular visual cortex. Dark exposure followed by reverse deprivation significantly enhances the strength of thalamocortical synaptic transmission and the density of dendritic spines on principle neurons throughout the depth of the visual cortex. Thus dark exposure reactivates widespread synaptic plasticity in the adult visual cortex, including at thalamocortical synapses, during the recovery from chronic monocular deprivation. PMID:21587234

  11. Protective effects of quercetine on the neuronal injury in frontal cortex after chronic toluene exposure.

    PubMed

    Kanter, Mehmet

    2013-08-01

    The aim of this study was designed to evaluate the possible protective effects of quercetine (QE) on the neuronal injury in the frontal cortex after chronic toluene exposure in rats. The rats were randomly allotted into one of the three experimental groups, namely, groups A (control), B (toluene treated) and C (toluene-treated with QE), where each group contains 10 animals. Control group received 1 ml of normal saline solution, and toluene treatment was performed by the inhalation of 3000 ppm toluene in an 8-h/day and 6-day/week order for 12 weeks. The rats in QE-treated group was given QE (15 mg/kg body weight) once a day intraperitoneally for 12 weeks, starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex after chronic toluene exposure in rats by QE treatment have been reported. In this study, the morphology of neurons in the QE treatment group was well protected. Chronic toluene exposure caused severe degenerative changes, shrunken cytoplasm and extensively dark picnotic nuclei in neurons of the frontal cortex. We conclude that QE therapy causes morphologic improvement in neurodegeneration of frontal cortex after chronic toluene exposure in rats. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats.

  12. Social Preference Deficits in Juvenile Zebrafish Induced by Early Chronic Exposure to Sodium Valproate

    PubMed Central

    Liu, Xiuyun; Zhang, Yinglan; Lin, Jia; Xia, Qiaoxi; Guo, Ning; Li, Qiang

    2016-01-01

    Prenatal exposure to sodium valproate (VPA), a widely used anti-epileptic drug, is related to a series of dysfunctions, such as deficits in language and communication. Clinical and animal studies have indicated that the effects of VPA are related to the concentration and to the exposure window, while the neurobehavioral effects of VPA have received limited research attention. In the current study, to analyze the neurobehavioral effects of VPA, zebrafish at 24 h post-fertilization (hpf) were treated with early chronic exposure to 20 μM VPA for 7 h per day for 6 days or with early acute exposure to 100 μM VPA for 7 h. A battery of behavioral screenings was conducted at 1 month of age to investigate social preference, locomotor activity, anxiety, and behavioral response to light change. A social preference deficit was only observed in animals with chronic VPA exposure. Acute VPA exposure induced a change in the locomotor activity, while chronic VPA exposure did not affect locomotor activity. Neither exposure procedure influenced anxiety or the behavioral response to light change. These results suggested that VPA has the potential to affect some behaviors in zebrafish, such as social behavior and the locomotor activity, and that the effects were closely related to the concentration and the exposure window. Additionally, social preference seemed to be independent from other simple behaviors. PMID:27812327

  13. Social Preference Deficits in Juvenile Zebrafish Induced by Early Chronic Exposure to Sodium Valproate.

    PubMed

    Liu, Xiuyun; Zhang, Yinglan; Lin, Jia; Xia, Qiaoxi; Guo, Ning; Li, Qiang

    2016-01-01

    Prenatal exposure to sodium valproate (VPA), a widely used anti-epileptic drug, is related to a series of dysfunctions, such as deficits in language and communication. Clinical and animal studies have indicated that the effects of VPA are related to the concentration and to the exposure window, while the neurobehavioral effects of VPA have received limited research attention. In the current study, to analyze the neurobehavioral effects of VPA, zebrafish at 24 h post-fertilization (hpf) were treated with early chronic exposure to 20 μM VPA for 7 h per day for 6 days or with early acute exposure to 100 μM VPA for 7 h. A battery of behavioral screenings was conducted at 1 month of age to investigate social preference, locomotor activity, anxiety, and behavioral response to light change. A social preference deficit was only observed in animals with chronic VPA exposure. Acute VPA exposure induced a change in the locomotor activity, while chronic VPA exposure did not affect locomotor activity. Neither exposure procedure influenced anxiety or the behavioral response to light change. These results suggested that VPA has the potential to affect some behaviors in zebrafish, such as social behavior and the locomotor activity, and that the effects were closely related to the concentration and the exposure window. Additionally, social preference seemed to be independent from other simple behaviors.

  14. Accidental mobile phone card ingestion

    PubMed Central

    Dixit, Sudesh; Mekwan, Jayanand; Brayley, Nigel F

    2009-01-01

    Accidental overdose, poisoning and foreign-body ingestion are common presentations to the emergency department. Usually, the ingested material is a common drug or household product. We present an unusual case of accidental ingestion where the foreign body was a mobile phone simulation (SIM) card. PMID:21686554

  15. 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.

  16. 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.

  17. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreased lung elastance.

    PubMed

    Hartney, John M; Chu, Hongwei; Pelanda, Roberta; Torres, Raul M

    2012-01-01

    Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks) exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmonary leukocyte infiltration together with measurements of lung elastance and pathology. This response was measured in both healthy wild type (C57BL/6) mice as well as mouse mutants deficient in the expression of Arhgef1 (Arhgef1(-/-)) that display constitutive pulmonary inflammation and decreased lung elastance reminiscent of emphysema. The results from this study show that sub-chronic second hand smoke exposure leads to significantly increased numbers of airspace leukocytes in both healthy and mutant animals. While sub-chronic cigarette smoke exposure is not sufficient to induce changes in lung architecture as measured by mean linear intercept, both groups exhibit a significant decrease in lung elastance. Together these data demonstrate that even sub-chronic exposure to second hand smoke is sufficient to induce pulmonary inflammation and decrease lung elastance in both healthy and diseased animals and in the absence of tissue destruction.

  18. 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

  19. Hypothalamic temperature: a key regulator in homeostatic restoration of sleep during chronic cold exposure in rats.

    PubMed

    Kaushik, Mahesh K; Kumar, Velayudhan Mohan; Mallick, Hruda Nanda

    2012-01-01

    Exposure to cold ambient temperature (Ta) affects sleep-wake (S-W) state. The vigilance states on the other hand influence thermal status of the animals. Simultaneous recording of body temperature (Tb) with S-W is crucial to understand the homeostatic relationship between the two. In the present study we recorded both Tb and hypothalamic temperature (Thy) along with S-W, during acute and chronic exposure to mild cold (Ta). Electrooculogram (EOG), electroencephalogram (EEG) and electromyogram (EMG) electrodes were chronically implanted in rats to assess S-W. A thermocouple, near the preoptic area, and radio transmitter in the peritoneum, were implanted, to record Thy and Tb respectively. After three days of baseline recordings of S-W, Thy and Tb at Ta of 26 dergrees C, the rats were exposed to mild cold Ta (18 degrees C) for 28 days. All the parameters were recorded during cold exposure and also for five days after the termination of cold exposure. On the first day of cold exposure there was a decrease in slow wave sleep and paradoxical sleep, but they were restored by the 21st day of continued exposure. The Thy remained decreased throughout the cold exposure. Though the Tb showed a slight decrease on the first day of cold exposure, there was no appreciable change during the subsequent days. The Thy came back to near pre exposure level on termination of cod exposure. The decrease in Thy during mild cold exposure would have triggered cold defense mechanisms. Increase in wakefulness during acute cold exposure and non-shivering thermogenesis during chronic cold exposure are probably responsible for the maintenance of Tb. Decrease in Thy is probably the key trigger for initiating thermoregulatory measures to maintain Tb and homeostatic restoration of sleep.

  20. Parameter evaluation and model validation of ozone exposure assessment using Harvard Southern California Chronic Ozone Exposure Study data.

    PubMed

    Xue, Jianping; Liu, Shi V; Ozkaynak, Halûk; Spengler, John D

    2005-10-01

    To examine factors influencing long-term ozone (O3) exposures by children living in urban communities, the authors analyzed longitudinal data on personal, indoor, and outdoor O3 concentrations, as well as related housing and other questionnaire information collected in the one-year-long Harvard Southern California Chronic Ozone Exposure Study. Of 224 children contained in the original data set, 160 children were found to have longitudinal measurements of O3 concentrations in at least six months of 12 months of the study period. Data for these children were randomly split into two equal sets: one for model development and the other for model validation. Mixed models with various variance-covariance structures were developed to evaluate statistically important predictors for chronic personal ozone exposures. Model predictions were then validated against the field measurements using an empirical best-linear unbiased prediction technique. The results of model fitting showed that the most important predictors for personal ozone exposure include indoor O3 concentration, central ambient O3 concentration, outdoor O3 concentration, season, gender, outdoor time, house fan usage, and the presence of a gas range in the house. Hierarchical models of personal O3 concentrations indicate the following levels of explanatory power for each of the predictive models: indoor and outdoor O3 concentrations plus questionnaire variables, central and indoor O3 concentrations plus questionnaire variables, indoor O3 concentrations plus questionnaire variables, central O3 concentrations plus questionnaire variables, and questionnaire data alone on time activity and housing characteristics. These results provide important information on key predictors of chronic human exposures to ambient O3 for children and offer insights into how to reliably and cost-effectively predict personal O3 exposures in the future. Furthermore, the techniques and findings derived from this study also have strong

  1. Chronic and Acute Effects of Coal Tar Pitch Exposure and Cardiopulmonary Mortality Among Aluminum Smelter Workers

    PubMed Central

    Friesen, Melissa C.; Demers, Paul A.; Spinelli, John J.; Eisen, Ellen A.; Lorenzi, Maria F.; Le, Nhu D.

    2010-01-01

    Air pollution causes several adverse cardiovascular and respiratory effects. In occupational studies, where levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) are higher, the evidence is inconsistent. The effects of acute and chronic PAH exposure on cardiopulmonary mortality were examined within a Kitimat, Canada, aluminum smelter cohort (n = 7,026) linked to a national mortality database (1957–1999). No standardized mortality ratio was significantly elevated compared with the province's population. Smoking-adjusted internal comparisons were conducted using Cox regression for male subjects (n = 6,423). Ischemic heart disease (IHD) mortality (n = 281) was associated with cumulative benzo[a]pyrene (B(a)P) exposure (hazard ratio = 1.62, 95% confidence interval: 1.06, 2.46) in the highest category. A monotonic but nonsignificant trend was observed with chronic B(a)P exposure and acute myocardial infarction (n = 184). When follow-up was restricted to active employment, the hazard ratio for IHD was 2.39 (95% confidence interval: 0.95, 6.05) in the highest cumulative B(a)P category. The stronger associations observed during employment suggest that risk may not persist after exposure cessation. No associations with recent or current exposure were observed. IHD was associated with chronic (but not current) PAH exposure in a high-exposure occupational setting. Given the widespread workplace exposure to PAHs and heart disease's high prevalence, even modest associations produce a high burden. PMID:20702507

  2. Reversible loss of reproductive fitness in zebrafish on chronic alcohol exposure.

    PubMed

    Dewari, Pooran Singh; Ajani, Funmilola; Kushawah, Gopal; Kumar, Damera Santhosh; Mishra, Rakesh K

    2016-02-01

    Alcoholism is one of the most prevalent diseases in society and causes significant health and social problems. Alcohol consumption by pregnant women is reported to cause adverse effects on the physical and psychological growth of the fetus. However, the direct effect of chronic alcohol consumption on reproductive fitness has not been tested. In recent years, the zebrafish (Danio rerio) has emerged as a versatile model system to study the effects of alcohol on behavior and embryonic development. We utilized the zebrafish model system to address the effect of chronic alcohol exposure (0.5% alcohol in the holding tank for 9 weeks) on reproductive capacity. We found a dramatic decrease in fecundity, measured by counting the number of eggs laid, when at least one of the parents is subject to chronic alcohol exposure. Interestingly, a 9-week alcohol withdrawal program completely restored the reproductive capacity of the treated subjects. In agreement with observations on fecundity, the chronic alcohol exposure leads to increased anxiety, as measured by the novel-tank diving assay. Conversely, the withdrawal program diminished heightened anxiety in alcohol-exposed subjects. Our results highlight the adverse effects of chronic alcohol exposure on the reproductive capacity of both males and females, and underscore the utility of the zebrafish model system to understand the biology of chronic alcoholism.

  3. Chronic pepsin exposure promotes anchorage-independent growth, and migration of a hypopharyngeal squamous cell line

    PubMed Central

    Kelly, Elizabeth A.; Samuels, Tina L.; Johnston, Nikki

    2015-01-01

    Outcome Objectives 1.Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. 2.Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony forming ability in hypopharyngeal cells. Study Design Translation research. Setting Academic research laboratory. Methods Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01mg/ml, 0.1 mg/ml, or 1mg/ml). Precise wounds were created in confluent cell plates and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony forming ability. Results An increased rate of relative wound density was observed in chronic pepsin treated (0.01mg/ml, 0.1mg/ml) cells compared to control (P<0.001), suggesting greater rates of cell migration. Pepsin treated (0.1 mg/ml) cells demonstrated on average, greater cell viability compared to control after exposure to paclitaxel suggesting possible apoptotic resistance, however this was not statistically significant. Chronic pepsin exposure (0.1mg/ml, 1mg/ml) was associated with dose dependent increase in colony forming ability relative to control (P<0.001). Conclusion Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration, and colony forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux. PMID:24376122

  4. Chronic pepsin exposure promotes anchorage-independent growth and migration of a hypopharyngeal squamous cell line.

    PubMed

    Kelly, Elizabeth A; Samuels, Tina L; Johnston, Nikki

    2014-04-01

    (1) Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. (2) Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony-forming ability in hypopharyngeal cells. Translation research. Academic research laboratory. Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01 mg/mL, 0.1 mg/mL, or 1 mg/mL). Precise wounds were created in confluent cell plates, and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin-exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony-forming ability. An increased rate of relative wound density was observed in chronic pepsin-treated (0.01 mg/mL, 0.1 mg/mL) cells compared with control (P < .001), suggesting greater rates of cell migration. Pepsin-treated (0.1 mg/mL) cells demonstrated on average greater cell viability compared with control after exposure to paclitaxel, suggesting possible apoptotic resistance; however, this was not statistically significant. Chronic pepsin exposure (0.1 mg/mL, 1 mg/mL) was associated with a dose-dependent increase in colony-forming ability relative to control (P < .001). Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration and colony-forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux.

  5. Consequences of acute and chronic exposure to arsenic in children.

    PubMed

    Calderon, Rebecca L; Abernathy, Charles O; Thomas, David J

    2004-07-01

    Arsenic is a toxic chemical and may cause adverse health effects in children and adults. It is known to affect the nervous, gastrointestinal, and hematological systems and cause skin and internal cancers in people exposed to levels greater than 300 ppb in their drinking water. For most people, the major exposure to arsenic comes from food (8 to 14 microg inorganic arsenic per day), but when the arsenic level in water is elevated, drinking water becomes the predominant source of exposure. Because it is very difficult to limit arsenic exposure from food, it would be wise to limit arsenic exposure from those more controllable sources. Pediatricians should ascertain the levels of arsenic in drinking water of patients with high arsenic levels, using the supplier or, in the case of private wells, a professional water-testing laboratory assay. The Safe Drinking Water Act does not cover private wells or those water systems with less than 15 hook-ups or those that serve less than 25 people. Pediatricians should instruct parents to use prepared baby formulas or prepare them using water with the arsenic removed and to curtail playing time for younger children in places that have sand containing large amounts of arsenic. Such procedures will limit arsenic exposure to a minimum.

  6. Regulatory frameworks for copper considering chronic exposures of the population.

    PubMed

    Cockell, Kevin A; Bertinato, Jesse; L'Abbé, Mary R

    2008-09-01

    Copper is an essential nutrient that is toxic in excess. Copper intakes from a balanced diet appear to meet the needs of most healthy individuals, because overt deficiency and toxicity are rare. Some uncertainty, however, persists because of limitations in currently available biomarkers used to assess copper status and the paucity of data available to establish tolerable upper levels of intake. Current policies and regulations pertaining to food fortification, nutritional supplements, and drinking water appear to be effective in providing for adequate copper intakes in many populations, although high levels of exposure, through overzealous fortification, supplementation, or drinking water exposure, may be possible under some circumstances. Surveillance and monitoring programs to evaluate copper exposures of human populations should continue and should be refined as new biomarkers become available.

  7. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro

    PubMed Central

    SCHERZAD, AGMAL; HACKENBERG, STEPHAN; FROELICH, KATRIN; RAK, KRISTEN; HAGEN, RUDOLF; TAEGER, JOHANNES; BREGENZER, MAXIMILLIAN; KLEINSASSER, NORBERT

    2016-01-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems. PMID:26998269

  8. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro.

    PubMed

    Scherzad, Agmal; Hackenberg, Stephan; Froelich, Katrin; Rak, Kristen; Hagen, Rudolf; Taeger, Johannes; Bregenzer, Maximillian; Kleinsasser, Norbert

    2016-03-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems.

  9. 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

  10. Acute and chronic respiratory effects of occupational exposure to ammonia.

    PubMed

    Holness, D L; Purdham, J T; Nethercott, J R

    1989-12-01

    In a soda ash plant, 58 workers exposed to mean airborne ammonia levels of 9.2 +/- 1.4 ppm were compared with 31 control workers with a mean exposure of 0.3 +/- 0.1 ppm. There were no differences between the groups in the reporting of respiratory or cutaneous symptoms, sense of smell, baseline lung function, or change in lung function over a work shift at the beginning and end of a workweek. No relationships between level or length of ammonia exposure and lung function results were demonstrated.

  11. Occupational exposures and chronic obstructive pulmonary disease (COPD): comparison of a COPD-specific job exposure matrix and expert-evaluated occupational exposures.

    PubMed

    Kurth, Laura; Doney, Brent; Weinmann, Sheila

    2017-03-01

    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. 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. 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. This COPD JEM was compared with exposures assigned by experts and offers a generalisable approach to assigning occupational exposure. 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/.

  12. 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

  13. Cardiovascular and renal effects of chronic exposure to high altitude.

    PubMed

    Hurtado, Abdias; Escudero, Elizabeth; Pando, Jackeline; Sharma, Shailendra; Johnson, Richard J

    2012-12-01

    Over 140 million people live at high altitude, defined as living at an altitude of 2400 m or more above sea level. Subjects living under these conditions are continuously living under hypoxic conditions and, depending on the population, various adaptations have developed. Interestingly, subjects living chronically at high altitude appear to have a decreased frequency of obesity, diabetes and coronary artery disease. However, these benefits on health are balanced by the frequent development of systemic and pulmonary hypertension. Recently, it has been recognized that subjects living at high altitude are at risk for developing high-altitude renal syndrome (HARS), which is a syndrome consisting of polycythemia, hyperuricemia, systemic hypertension and microalbuminuria, but with preserved glomerular filtration rate. More studies should be performed to characterize the mechanisms and etiology of HARS; as such studies may be of benefit not only to the high-altitude population, but also to better understanding of the renal consequences of acute and chronic hypoxia.

  14. 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.

  15. Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits

    PubMed Central

    Vieira-Brock, Paula L.; McFadden, Lisa M.; Nielsen, Shannon M.; Ellis, Jonathan D.; Walters, Elliot T.; Stout, Kristen A.; McIntosh, J. Michael; Wilkins, Diana G.; Hanson, Glen R.

    2015-01-01

    Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson’s disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [125I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [125I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection. PMID:26391161

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

    PubMed

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

    2017-02-07

    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/m(3), SOA (30 μg/m(3)) + 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.

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

    PubMed Central

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

    2017-01-01

    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. PMID:28169367

  18. 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.

  19. Accidental dapsone poisoning in children.

    PubMed

    Nair, P M; Philip, E

    1984-12-01

    Accidental poisoning in children shows a trend towards poisoning with various newer drugs and chemicals used in the household. Sixty-one cases of accidental poisoning in children were seen in Sree Avittam Thirunal Hospital, (S.A.T.H.), Trivandrum, South India during the year 1982, constituting 0.61% of the total pediatric admissions. Dapsone poisoning constituted 9.8% of the total accidental poisonings, emphasising the need for safe storage of drugs out of the reach of young children. Dapsone poisoning with resultant methaemoglobinaemia responded well to intravenous ascorbic acid and other supportive measures.

  20. Pulmonary sensitivity to ozone exposure in sedentary versus chronically trained, female rats

    EPA Pesticide Factsheets

    Pulmonary effects to ozone with rats that have chronically exercised or have been continuously sedentary. Also includes body composition of both groups throughout experimentation.This dataset is associated with the following publication:Gordon , C., P. Phillips , T. Beasley , A. Ledbetter , A. Cenk, U. Kodavanti , and A. Johnstone. Pulmonary Sensitivity to Ozone Exposure in Sedentary Versus Chronically Trained, Female Rats. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, USA, 293-302, (2016).

  1. 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...

  2. 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. ...

  3. 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...

  4. 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. ...

  5. 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

  6. Chronic low dose chlorine exposure aggravates allergic inflammation and airway hyperresponsiveness and activates inflammasome pathway.

    PubMed

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

    2014-01-01

    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). 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. 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. Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways.

  7. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis

    SciTech Connect

    Wahl, Elizabeth C.; Aronson, James; Liu, Lichu; Liu, Zhendong; Perrien, Daniel S.; Skinner, Robert A.; Badger, Thomas M.; Ronis, Martin J.J.; Lumpkin, Charles K. . E-mail: lumpkincharlesk@uams.edu

    2007-05-01

    Tumor necrosis factor-alpha (TNF-{alpha}) is an inflammatory cytokine that modulates osteoblastogenesis. In addition, the demonstrated inhibitory effects of chronic ethanol exposure on direct bone formation in rats are hypothetically mediated by TNF-{alpha} signaling. The effects in mice are unreported. Therefore, we hypothesized that in mice (1) administration of a soluble TNF receptor 1 derivative (sTNF-R1) would protect direct bone formation during chronic ethanol exposure, and (2) administration of recombinant mouse TNF-{alpha} (rmTNF-{alpha}) to ethanol naive mice would inhibit direct bone formation. We utilized a unique model of limb lengthening (distraction osteogenesis, DO) combined with liquid diets to measure chronic ethanol's effects on direct bone formation. Chronic ethanol exposure resulted in increased marrow TNF, IL-1, and CYP 2E1 RNA levels in ethanol-treated vs. control mice, while no significant weight differences were noted. Systemic administration of sTNF-R1 during DO (8.0 mg/kg/2 days) to chronic ethanol-exposed mice resulted in enhanced direct bone formation as measured radiologically and histologically. Systemic rmTNF-{alpha} (10 {mu}g/kg/day) administration decreased direct bone formation measures, while no significant weight differences were noted. We conclude that chronic ethanol-associated inhibition of direct bone formation is mediated to a significant extent by the TNF signaling axis in a mouse model.

  8. Neurotoxicity of chronic low-dose exposure to organic solvents: a skeptical review.

    PubMed

    Lees-Haley, P R; Williams, C W

    1997-11-01

    The health effects of long-term, low-level exposure to organic solvents have been studied for many years. While the volume of literature is great, definitive conclusions regarding chronic neurobehavioral effects of environmental exposure are premature. Methodological shortcomings in research preclude confidence in studies allegedly supporting a causal link between chronic low-dose solvent exposure and lasting neurobehavioral deficits. In this article, the shortcomings reviewed include selection bias in recruitment of research subjects, overreliance on subjective recall in determining levels and duration of exposure, between-study variability in kinds of solvents examined, variability in tests selected to assess neurobehavioral functioning, and diversity in reported findings. The implications of these for characterizing the state of organic solvent research are discussed.

  9. GABA and Dopamine Release from Different Brain Regions in Mice with Chronic Exposure to Organophosphate Methamidophos

    PubMed Central

    Noriega-Ortega, Blanca Rosa; Armienta-Aldana, Ernesto; Cervantes-Pompa, José Ángel; Armienta-Aldana, Eduardo; Hernández-Ruíz, Enrique; Chaparro-Huerta, Verónica; Bravo-Cuellar, Alejandro; Beas-Zárate, Carlos

    2011-01-01

    Organophosphates such as methamidophos, usually used in the agricultural field, have harmful effects on humans. Exposures to insecticides has been associated with many disorders, including damage to the central and peripheral nervous system. Chronic exposure to organophosphates may lead to persistent neurological and neurobehavioral effects. This study was conducted to determine the effect of methamidophos on [3H]-dopamine (DA) and gamma aminobutyric acid (GABA) release from different brain regions after chronic exposure to it for 3, 6 or 9 months. After a six-month methamidophos treatment, the mice showed high susceptibility to convulsive seizures and a reduction in stimulated gamma aminobutyric acid release from the cerebral cortex and hippocampal slices, whereas stimulated (DA) release was slightly decreased from the striatum after three months of methamidophos exposure. The results indicate changes in gamma aminobutyric acid and dopamine neurotransmission, suggesting a specific neuronal damage. PMID:22272056

  10. Controlled exposure of volunteers with chronic obstructive pulmonary disease to sulfur dioxide

    SciTech Connect

    Linn, W.S.; Fischer, D.A.; Shamoo, D.A.; Spier, C.E.; Valencia, L.M.; Anzar, U.T.; Hackney, J.D.

    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. Older 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.

  11. 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

    2017-02-09

    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;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.

  12. Secondhand smoke exposure is associated with proteinuria in children with chronic kidney disease.

    PubMed

    Omoloja, Abiodun; Jerry-Fluker, Judith; Ng, Derek K; Abraham, Alison G; Furth, Susan; Warady, Bradley A; Mitsnefes, Mark

    2013-08-01

    In adults with chronic kidney disease (CKD), cigarette smoking is associated with an increased risk for CKD progression and transplant failure. In children, secondhand smoke (SHS) exposure has been associated with elevated blood pressure. There are no studies on the prevalence and effect of SHS exposure in CKD. Subjects were enrolled in the Chronic Kidney Disease in Children (CKiD) Study, an observational cohort of 366 children aged 1 to 16 years with CKD. Secondhand smoke exposure was obtained via questionnaire. SHS exposure was also determined based on urine cotinine (Ucot) measurements (1 ng/mL ≤ Ucot < 75 ng/mL). The cross-sectional association of SHS exposure with proteinuria was assessed. Using Ucot, 22 % of subjects were exposed to SHS. SHS exposure was significantly associated with lower maternal education and African American race, and a greater prevalence of nephrotic range proteinuria and left ventricular hypertrophy. In a multivariate model (including sex, age, race, maternal education, income level, private insurance status, abnormal birth history and CKD diagnosis), the prevalence odds of nephrotic range proteinuria was 2.64, (95 % confidence interval 1.08, 6.42) higher in children exposed to SHS compared to those unexposed. In our cohort of children with CKD, SHS exposure was common (22 %) and independently associated with nephrotic range proteinuria. Exposure to SHS may be an important factor to consider in CKD progression.

  13. Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease

    PubMed Central

    Eisner, Mark D; Balmes, John; Katz, Patricia P; Trupin, Laura; Yelin, Edward H; Blanc, Paul D

    2005-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:15890079

  14. Short term hardening effects on survival of acute and chronic cold exposure by Drosophila melanogaster larvae

    PubMed Central

    Rajamohan, Arun; Sinclair, Brent J.

    2008-01-01

    We quantified the variation and plasticity in cold tolerance among four larval stages of four laboratory strains of Drosophila melanogaster in response to both acute (<2 hours of cold exposure) and chronic (∼7 hours of cold exposure) cold exposure. We observed significant differences in basal cold tolerance between the strains and among larval stages. Early larval instars were generally more tolerant of acute cold exposures than 3rd instar larvae. However, wandering larvae were more tolerant of chronic cold exposures than the other stages. Early stages also displayed a more pronounced rapid cold-hardening response than the later stages. Heat pre-treatment did not confer a significant increase in cold tolerance to any of the strains at any stage, pointing to different mechanisms being involved in resolving heat- and cold-elicited damage. However, when heat pre-treatment was combined with rapid cold-hardening as sequential pre-treatments, both positive (heat first) and negative (heat second) effects on cold tolerance were observed. We discuss possible mechanisms underlying cold-hardening and the effects of acute and chronic cold exposures. PMID:18342328

  15. Chronic exposure of rats to occupational textile noise causes cytological changes in adrenal cortex.

    PubMed

    Oliveira, Maria Joao R; Monteiro, Mariana P; Ribeiro, Andreia M; Pignatelli, Duarte; Aguas, Artur P

    2009-01-01

    Chronic exposure to industrial noise and its effects on biological systems. Occupational exposure to noise may result in health disorders. Our aim was to evaluate the effects of chronic exposure to high-intensity noise of textile industry cotton rooms on the adrenal morphology. The environmental noise of a cotton-mill room from a large textile factory of Northern Portugal was recorded and reproduced by an adopted electroacoustic setup in a sound-insulated animal room where the rats were housed. The sounds were reproduced at the original levels of approximately 92 dB, which was achieved by equalization and distribution of sound output in the room. Wistar rats were submitted to noise exposure, in the same time schedule as employed in textile plants. After one, three, five, and seven months, the adrenals were collected and analyzed by light microscopy. Analyzed by multivariate analysis of variance and post hoc Bonferroni correction for multiple comparisons of the means between the groups. Noise exposure induced time-dependent changes in adrenal cortex, with decrease of zona fasciculata (ZF) and increase of zona reticularis volumes, together with a significant depletion of lipid droplet density in ZF cells of exposed rats, in comparison to control rats. Chronic exposure of rats to textile industry noise triggers cytological changes in the adrenals that suggest the existence of a sustained stress response.

  16. CHRONIC INTERMITTENT ETHANOL EXPOSURE REDUCES PRESYNAPTIC DOPAMINE NEUROTRANSMISSION IN THE MOUSE NUCLEUS ACCUMBENS

    PubMed Central

    Karkhanis, Anushree N.; Rose, Jamie H.; Huggins, Kimberly N.; Konstantopoulos, Joanne K.; Jones, Sara R.

    2015-01-01

    BACKGROUND Increasing evidence suggests that chronic ethanol exposure decreases dopamine (DA) neurotransmission in the nucleus accumbens (NAc), contributing to a hypodopaminergic state during withdrawal. However, few studies have investigated adaptations in presynaptic DA terminals after chronic intermittent ethanol (CIE) exposure. In monkeys and rats, chronic ethanol exposure paradigms have been shown to increase DA uptake and D2 autoreceptor sensitivity. METHODS The current study examined the effects of ethanol on DA terminals in CIE exposed mice during two time-points after the cessation of CIE exposure. DA release and uptake were measured using fast scan cyclic voltammetry in NAc core slices from C57BL/6J mice, 0 and 72 hours following three weekly cycles (4 days of 16 hrs ethanol vapor/8 hrs room air/day + 3 days withdrawal) of CIE vapor exposure. RESULTS Current results showed that DA release was reduced, uptake rates were increased, and inhibitory D2-type autoreceptor activity was augmented following CIE exposure in mice. CONCLUSIONS Overall, these CIE-induced adaptations in the accumbal DA system reduce DA signaling and therefore reveal several potential mechanisms contributing to a functional hypodopaminergic state during alcohol withdrawal. PMID:25765483

  17. Chronic intermittent ethanol exposure reduces presynaptic dopamine neurotransmission in the mouse nucleus accumbens.

    PubMed

    Karkhanis, Anushree N; Rose, Jamie H; Huggins, Kimberly N; Konstantopoulos, Joanne K; Jones, Sara R

    2015-05-01

    Increasing evidence suggests that chronic ethanol exposure decreases dopamine (DA) neurotransmission in the nucleus accumbens (NAc), contributing to a hypodopaminergic state during withdrawal. However, few studies have investigated adaptations in presynaptic DA terminals after chronic intermittent ethanol (CIE) exposure. In monkeys and rats, chronic ethanol exposure paradigms have been shown to increase DA uptake and D2 autoreceptor sensitivity. The current study examined the effects of ethanol on DA terminals in CIE exposed mice during two time-points after the cessation of CIE exposure. DA release and uptake were measured using fast scan cyclic voltammetry in NAc core slices from C57BL/6J mice, 0h and 72h following three weekly cycles (4 days of 16h ethanol vapor/8h room air/day+3 days withdrawal) of CIE vapor exposure. Current results showed that DA release was reduced, uptake rates were increased, and inhibitory D2-type autoreceptor activity was augmented following CIE exposure in mice. Overall, these CIE-induced adaptations in the accumbal DA system reduce DA signaling and therefore reveal several potential mechanisms contributing to a functional hypodopaminergic state during alcohol withdrawal. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. The West London Schools Study: the effects of chronic aircraft noise exposure on child health.

    PubMed

    Haines, M M; Stansfeld, S A; Brentnall, S; Head, J; Berry, B; Jiggins, M; Hygge, S

    2001-11-01

    Previous field studies have indicated that children's cognitive performance is impaired by chronic aircraft noise exposure. However, these studies have not been of sufficient size to account adequately for the role of confounding factors. The objective of this study was to test whether cognitive impairments and stress responses (catecholamines, cortisol and perceived stress) are attributable to aircraft noise exposure after adjustment for school and individual level confounding factors and to examine whether children exposed to high levels of social disadvantage are at greater risk of noise effects. The cognitive performance and health of 451 children aged 8-11 years, attending 10 schools in high aircraft noise areas (16 h outdoor Leq > 63 dBA) was compared with children attending 10 matched control schools exposed to lower levels of aircraft noise (16 h outdoor Leq < 57 dBA). Noise exposure was associated with impaired reading on difficult items and raised annoyance, after adjustment for age, main language spoken and household deprivation. There was no variation in the size of the noise effects in vulnerable subgroups of children. High levels of noise exposure were not associated with impairments in mean reading score, memory and attention or stress responses. Aircraft noise was weakly associated with hyperactivity and psychological morbidity. Chronic noise exposure is associated with raised noise annoyance in children. The cognitive results indicate that chronic aircraft noise exposure does not always lead to generalized cognitive effects but, rather, more selective cognitive impairments on difficult cognitive tests in children.

  19. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala.

    PubMed

    Pleil, Kristen E; Lowery-Gionta, Emily G; Crowley, Nicole A; Li, Chia; Marcinkiewcz, Catherine A; Rose, Jamie H; McCall, Nora M; Maldonado-Devincci, Antoniette M; Morrow, A Leslie; Jones, Sara R; Kash, Thomas L

    2015-12-01

    Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (lCeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry.

  20. Effect of chronic exposure to rimonabant and phytocannabinoids on anxiety-like behavior and saccharin palatability.

    PubMed

    O'Brien, Lesley D; Wills, Kiri L; Segsworth, Blair; Dashney, Brittany; Rock, Erin M; Limebeer, Cheryl L; Parker, Linda A

    2013-01-01

    The acute effects of cannabinoid compounds have been investigated in animal models of anxiety-like behavior and palatability processing. However, the chronic effects of cannabinoids in such models are poorly understood. Experiment 1 compared the effects of both acute and chronic (14 days) exposure to the CB(1) receptor inverse agonist/antagonist, rimonabant, and the cannabis-derived CB(1) receptor neutral antagonist, tetrahydrocannabivarin (THCV), on: 1) time spent in the open, lit box in the Light-Dark (LD) immersion model of anxiety-like behavior and 2) saccharin hedonic reactions in the taste reactivity (TR) test of palatability processing. Experiment 2 compared the effects of chronic administration of cannabis-derived Δ(9)-tetrahydrocannabinol (Δ(9)-THC), cannabidiol (CBD) and cannabigerol (CBG) in these models. Tests were administered on Days 1, 7 and 14 of drug administration. In Experiment 1, rimonabant, but not THCV, produced an anxiogenic-like reaction in the LD immersion test and reduced saccharin palatability in the TR test; both of these effects occurred acutely and were not enhanced by chronic exposure. In Experiment 2, Δ(9)-THC also produced an acute anxiogenic-like reaction in the LD immersion test, without enhancement by chronic exposure. However, Δ(9)-THC enhanced saccharin palatability in the TR test on Day 1 of drug exposure only. CBD and CBG did not modify anxiety-like responding, but CBG produced a weak enhancement of saccharin palatability on Day 1 only. The results suggest that the anxiogenic-like reactions and the suppression of hedonic responding produced by rimonabant, are mediated by inverse agonism of the CB(1) receptor and these effects are not enhanced with chronic exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala

    PubMed Central

    Pleil, Kristen E.; Lowery-Gionta, Emily G.; Crowley, Nicole A.; Li, Chia; Marcinkiewcz, Catherine A.; Rose, Jamie H.; McCall, Nora M.; Maldonado-Devincci, Antoniette M.; Morrow, A. Leslie; Jones, Sara R.; Kash, Thomas L.

    2016-01-01

    Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (lCeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry. PMID:26188147

  2. [My accidental discovery].

    PubMed

    Nakamura, Tatsuya

    2008-10-01

    gleaned from my one accidental discovery.

  3. The Paradoxical Effects of Chronic Intra-Amniotic Ureaplasma parvum Exposure on Ovine Fetal Brain Development.

    PubMed

    Gussenhoven, Ruth; Ophelders, Daan R M G; Kemp, Matthew W; Payne, Matthew S; Spiller, Owen B; Beeton, Michael L; Stock, Sarah J; Cillero-Pastor, Bertha; Barré, Florian P Y; Heeren, Ron M A; Kessels, Lilian; Stevens, Bas; Rutten, Bart P; Kallapur, Suhas G; Jobe, Alan H; Kramer, Boris W; Wolfs, Tim G A M

    2017-08-29

    Chorioamnionitis is associated with adverse neurodevelopmental outcomes in preterm infants. Ureaplasma spp. are the microorganisms most frequently isolated from the amniotic fluid of women diagnosed with chorioamnionitis. However, controversy remains concerning the role of Ureaplasma spp. in the pathogenesis of neonatal brain injury. We hypothesize that reexposure to an inflammatory trigger during the perinatal period might be responsible for the variation in brain outcomes of preterms following Ureaplasma-driven chorioamnionitis. To investigate these clinical scenarios, we performed a detailed multimodal study in which ovine neurodevelopmental outcomes were assessed following chronic intra-amniotic Ureaplasma parvum (UP) infection either alone or combined with subsequent lipopolysaccharide (LPS) exposure. We show that chronic intra-amniotic UP exposure during the second trimester provoked a decrease in astrocytes, increased oligodendrocyte numbers, and elevated 5-methylcytosine levels. In contrast, short-term LPS exposure before preterm birth induced increased microglial activation, myelin loss, elevation of 5-hydroxymethylcytosine levels, and lipid profile changes. These LPS-induced changes were prevented by chronic preexposure to UP (preconditioning). These data indicate that chronic UP exposure has dual effects on preterm brain development in utero. On the one hand, prolonged UP exposure causes detrimental cerebral changes that may predispose to adverse postnatal clinical outcomes. On the other, chronic intra-amniotic UP exposure preconditions the brain against a second inflammatory hit. This study demonstrates that microbial interactions and the timing and duration of the inflammatory insults determine the effects on the fetal brain. Therefore, this study helps to understand the complex and diverse postnatal neurological outcomes following UP driven chorioamnionitis. © 2017 S. Karger AG, Basel.

  4. Behavioral and neurochemical changes in response to acute stressors: influence of previous chronic exposure to immobilization.

    PubMed

    Pol, O; Campmany, L; Gil, M; Armario, A

    1992-07-01

    The effect of daily (2 h) exposure to immobilization (IMO) for 15 days on the behavioral and neurochemical responses of adult male rats to acute stress caused by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic exposure to IMO did not alter noradrenaline (NA), 3-methoxy,4-hydroxyphenyletileneglycol-SO4 (MHPG-SO4), serotonin, or 5-hydroxindoleacetic acid (5-HIAA) concentrations in any brain area as measured approximately 20 h after the last exposure to IMO. Exposure to behavioral tests did not modify neurochemical variables except NA levels in the hypothalamus of nonchronically stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats. These decreases in response to the two acute stressors were not observed in chronically stressed rats. However, MHPG-SO4 levels increased to the same extent in control and chronically stressed rats after exposure to the acute stressors. Likewise, increased 5-HIAA concentrations observed in response to acute stressors were similar in control and chronically stressed rats. The inhibition of activity (areas crossed and rearing) in the holeboard caused by acute IMO was less marked in rats previously exposed to the same stressor than in control rats, but the response to shock was similar. In the forced swim test, acute IMO decreased struggling in control rats but tended to increase it in chronically stressed rats. The response to shock followed the same pattern as that to IMO, although it was slight.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Chronic occupational exposure to asbestos: more than medical effects

    SciTech Connect

    Lebovits, A.H.; Byrne, M.; Bernstein, J.; Strain, J.J.

    1988-01-01

    One hundred and twenty-nine workers chronically exposed to asbestos were interviewed regarding their perceived health status and concerns, their health behaviors, particularly their smoking behavior, and their psychologic well-being. In contrast to a non-exposed comparison group of postal workers, asbestos workers exhibited significantly elevated levels of somatic concern (P less than .03), and significantly lower levels of mental health functioning only when experiencing high levels of stress (P less than .01). Despite feeling significantly more susceptible to developing cancer (P less than .0001), 34% of asbestos workers were cigarette smokers (compared to 32% of the postal group) and long-term mask usage was minimal. Asbestos workers' increased sensitivity to stress and changes in health status along with the lack of adaptation of health-promotive behaviors indicate the need for interventions to attend to the psychologic effects of increased risk status.

  6. Effects of chronic boron exposure on semen profile.

    PubMed

    Korkmaz, Mehmet; Yenigün, Mehmet; Bakırdere, Sezgin; Ataman, Osman Yavuz; Keskin, Sıddık; Müezzinoğlu, Talha; Lekili, Murat

    2011-11-01

    The possible changes in semen quality were studied in men living in a boron mining area. The subjects in the boron group had exposure to boron at an average level of 6.5 mg/day, as determined by urinary analysis. The results obtained by the boron group were compared to those obtained for the control group whose subjects were living in the same geographical area but away from the boron region; average exposure level was 1.4 mg/day for this group. The semen samples were analyzed according to the recommendations of the World Health Organization. Boron levels were established in the water samples obtained from various locations in the study region. In the boron mining fields where the subjects in the boron group live, water samples contained boron in the range of 1.4-6.5 mg/L, while the values were <0.01 mg/L for the water samples obtained from the region where the subjects of the control group reside. No negative effects were found in the sperm samples obtained from the subjects of the boron group.

  7. [Pansclerotic porphyria cutanea tarda after chronic exposure to organic solvents].

    PubMed

    Karamfilov, T; Buslau, M; Dürr, C; Weyers, W

    2003-05-01

    A 63 year old man developed generalized scleroderma with massive sclerotic areas, particularly in the abdominal region, four years after being diagnosed with porphyria cutanea tarda (PCT). He had almost daily exposure to organic solvents (benzene, trichlorethylene) for many years. The cutaneous fibrosis progressed dramatically leading to a pansclerosis, even though the uroporphyrin levels were borderline and the liver enzyme values were normal. Organic solvents are among those substances which can cause a cutaneous fibrosis. The unusually complicated clinical development in our patient was a combination of the two initial factors, the PCT and the long term exposure to organic solvents. The pansclerotic PCT was differentiated from a systemic sclerosis, a disabling pansclerotic morphea and a generalized morphea by means of histological examinations, the absence of a Raynaud phenomenon and the non-involvement of additional organs. Auto-antibodies typical for systemic sclerosis were negative. Using a medium dosage of UVA1 phototherapy and intensive physiotherapy, the progression of the skin disease was stopped and the sclerosis improved.

  8. 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

  9. 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.

  10. 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

  11. Inequitable Chronic Lead Exposure: A Dual Legacy of Social and Environmental Injustice.

    PubMed

    Leech, Tamara G J; Adams, Elizabeth A; Weathers, Tess D; Staten, Lisa K; Filippelli, Gabriel M

    2016-01-01

    Both historic and contemporary factors contribute to the current unequal distribution of lead in urban environments and the disproportionate impact lead exposure has on the health and well-being of low-income minority communities. We consider the enduring impact of lead through the lens of environmental justice, taking into account well-documented geographic concentrations of lead, legacy sources that produce chronic exposures, and intergenerational transfers of risk. We discuss the most promising type of public health action to address inequitable lead exposure and uptake: primordial prevention efforts that address the most fundamental causes of diseases by intervening in structural and systemic inequalities.

  12. Acute and Chronic Exposure to CO2 in Space Flight

    NASA Technical Reports Server (NTRS)

    Alexander, D.; Wu, J.; Barr, Y. R.; Watkins, S. D.

    2010-01-01

    Spacecraft and space stations, similar to other habitable confined spaces such as submarines, need to provide a breathable atmosphere for their inhabitants. The inevitable production of CO2 during respiration necessitates life support systems that "scrub" the atmosphere and lower CO2 levels. Due to operational limitations associated with space flight (limited mass, volume, power, and consumables) CO2 is not scrubbed down to its terrestrial equivalent of 0.03% CO2 (ppCO2 of 0.23 mmHg), but is kept below 0.7% (ppCO2 of 5.3 mmHg), a level established in NASA s 180-day mission Spacecraft Maximum Allowable Concentration (SMAC) to be safe and unlikely to cause symptoms. Reports of space flight crewmembers becoming symptomatic with headaches, fatigue, and malaise at levels below those known to cause such symptoms terrestrially has prompted studies measuring the levels of CO2 on both the space shuttle and the space station. Data from cabin atmosphere sampling were collected on space shuttle missions STS-113, STS-122, STS-123, and International Space Station Expeditions 12-15 and 17, and the measured CO2 levels were then correlated to symptoms reported by the crew. The results indicate that a correlation exists between CO2 levels and symptomatology, however causality cannot be established at this time. While the short-term effects of elevated CO2 exposure are well known terrestrially, less is known regarding potential long-term effects of prolonged exposure to a CO2-rich environment or how the physiological changes caused by microgravity may interact with such exposures. Other challenges include limitations in the CO2 monitors used, lack of convection in the microgravity environment, and formation of localized CO2 pockets. As it is unclear if the unique environment of space increases sensitivity to CO2 or if other confounding factors are present, further research is planned to elucidate these points. At the same time, efforts are underway to update the SMAC to a lower level

  13. Influence of environmental exposures on patients with chronic obstructive pulmonary disease in Korea.

    PubMed

    Hong, Yoonki; Lim, Myoung Nam; Kim, Woo Jin; Rhee, Chin Kook; Yoo, Kwang Ha; Lee, Ji-Hyun; Yoon, Ho Il; Kim, Tae-Hyung; Lee, Jin Hwa; Lim, Seong Yong; Lee, Sang Do; Oh, Yeon-Mok

    2014-05-01

    Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposures can influence COPD. The purpose of this study is to investigate the clinical characteristics of COPD according to the history of environmental exposure. The study population comprised of 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals within the Korean Obstructive Lung Disease Study Group. We classified environmental exposures according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life, exercise capacity, and computed tomography phenotypes. Thirty-one subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure history to briquette, and 184 (53.3%) had exposure history to firewood. Patients with history of living near a factory had a significantly longer duration of sputum, while patients with exposure to firewood tended to have lower forced expiratory volume in one second, and patients with exposure to briquette tended to have lower six minute walk distance. COPD subjects with the history of living near factory had more frequent respiratory symptoms such as sputum. Our data suggest that environmental exposure may influence clinical phenotype of COPD.

  14. 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...

  15. 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...

  16. 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…

  17. 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...

  18. 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...

  19. 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 ...

  20. 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.

  1. 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...

  2. 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…

  3. 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 ...

  4. Chronic Exposure to Particulate Chromate Induces Premature Centrosome Separation and Centriole Disengagement in Human Lung Cells

    PubMed Central

    Martino, Julieta; Holmes, Amie L.; Xie, Hong; Wise, Sandra S.; Wise, John Pierce

    2015-01-01

    Particulate hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen. Lung tumors are characterized by structural and numerical chromosome instability. Centrosome amplification is a phenotype commonly found in solid tumors, including lung tumors, which strongly correlates with chromosome instability. Human lung cells exposed to Cr(VI) exhibit centrosome amplification but the underlying phenotypes and mechanisms remain unknown. In this study, we further characterize the phenotypes of Cr(VI)-induced centrosome abnormalities. We show that Cr(VI)-induced centrosome amplification correlates with numerical chromosome instability. We also show chronic exposure to particulate Cr(VI) induces centrosomes with supernumerary centrioles and acentriolar centrosomes in human lung cells. Moreover, chronic exposure to particulate Cr(VI) affects the timing of important centriolar events. Specifically, chronic exposure to particulate Cr(VI) causes premature centriole disengagement in S and G2 phase cells. It also induces premature centrosome separation in interphase. Altogether, our data suggest that chronic exposure to particulate Cr(VI) targets the protein linkers that hold centrioles together. These centriolar linkers are important for key events of the centrosome cycle and their premature disruption might underlie Cr(VI)-induced centrosome amplification. PMID:26293554

  5. 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...

  6. 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

  7. Challenges Associated with Exposure to Chronic Trauma: Using a Public Health Framework to Foster Resilient Outcomes among Youth

    ERIC Educational Resources Information Center

    Overstreet, Stacy; Mathews, Tara

    2011-01-01

    For many children, trauma exposure is a common and chronic experience. Chronic trauma exposure during childhood significantly increases the risk for emotional/behavioral disorders and academic failure. There is a critical need for school psychologists, and the schools in which they work, to understand the unique needs of students with or at risk…

  8. Challenges Associated with Exposure to Chronic Trauma: Using a Public Health Framework to Foster Resilient Outcomes among Youth

    ERIC Educational Resources Information Center

    Overstreet, Stacy; Mathews, Tara

    2011-01-01

    For many children, trauma exposure is a common and chronic experience. Chronic trauma exposure during childhood significantly increases the risk for emotional/behavioral disorders and academic failure. There is a critical need for school psychologists, and the schools in which they work, to understand the unique needs of students with or at risk…

  9. No effect of low-level chronic neonicotinoid exposure on bumblebee learning and fecundity.

    PubMed

    Piiroinen, Saija; Botías, Cristina; Nicholls, Elizabeth; Goulson, Dave

    2016-01-01

    In recent years, many pollinators have declined in abundance and diversity worldwide, presenting a potential threat to agricultural productivity, biodiversity and the functioning of natural ecosystems. One of the most debated factors proposed to be contributing to pollinator declines is exposure to pesticides, particularly neonicotinoids, a widely used class of systemic insecticide. Also, newly emerging parasites and diseases, thought to be spread via contact with managed honeybees, may pose threats to other pollinators such as bumblebees. Compared to honeybees, bumblebees could be particularly vulnerable to the effects of stressors due to their smaller and more short-lived colonies. Here, we studied the effect of field-realistic, chronic clothianidin exposure and inoculation with the parasite Nosema ceranae on survival, fecundity, sugar water collection and learning using queenless Bombus terrestris audax microcolonies in the laboratory. Chronic exposure to 1 ppb clothianidin had no significant effects on the traits studied. Interestingly, pesticide exposure in combination with additional stress caused by harnessing bees for Proboscis Extension Response (PER) learning assays, led to an increase in mortality. In contrast to previous findings, the bees did not become infected by N. ceranae after experimental inoculation with the parasite spores, suggesting variability in host resistance or parasite virulence. However, this treatment induced a slight, short-term reduction in sugar water collection, potentially through stimulation of the immune system of the bees. Our results suggest that chronic exposure to 1 ppb clothianidin does not have adverse effects on bumblebee fecundity or learning ability.

  10. No effect of low-level chronic neonicotinoid exposure on bumblebee learning and fecundity

    PubMed Central

    Botías, Cristina; Nicholls, Elizabeth; Goulson, Dave

    2016-01-01

    In recent years, many pollinators have declined in abundance and diversity worldwide, presenting a potential threat to agricultural productivity, biodiversity and the functioning of natural ecosystems. One of the most debated factors proposed to be contributing to pollinator declines is exposure to pesticides, particularly neonicotinoids, a widely used class of systemic insecticide. Also, newly emerging parasites and diseases, thought to be spread via contact with managed honeybees, may pose threats to other pollinators such as bumblebees. Compared to honeybees, bumblebees could be particularly vulnerable to the effects of stressors due to their smaller and more short-lived colonies. Here, we studied the effect of field-realistic, chronic clothianidin exposure and inoculation with the parasite Nosema ceranae on survival, fecundity, sugar water collection and learning using queenless Bombus terrestris audax microcolonies in the laboratory. Chronic exposure to 1 ppb clothianidin had no significant effects on the traits studied. Interestingly, pesticide exposure in combination with additional stress caused by harnessing bees for Proboscis Extension Response (PER) learning assays, led to an increase in mortality. In contrast to previous findings, the bees did not become infected by N. ceranae after experimental inoculation with the parasite spores, suggesting variability in host resistance or parasite virulence. However, this treatment induced a slight, short-term reduction in sugar water collection, potentially through stimulation of the immune system of the bees. Our results suggest that chronic exposure to 1 ppb clothianidin does not have adverse effects on bumblebee fecundity or learning ability. PMID:27014515

  11. Gene-environment interaction between angiotensinogen and chronic exposure to occupational noise contribute to hypertension.

    PubMed

    Hwang, Bing-Fang; Chang, Ta-Yuan; Cheng, Kang-Yin; Liu, Chiu-Shong

    2012-04-01

    Previous studies on the effects of angiotensinogen (AGT) gene polymorphisms and chronic exposure to occupational noise on the risk of hypertension have mainly been cross-sectional or prevalent case-control studies, where temporality constitutes problems. The present study was to assess longitudinally both independent and joint effects of AGT gene polymorphisms and chronic exposure to occupational noise on occurrence of hypertension. The authors conducted a 20-year prospective cohort study of 1301 aviation workers in Taiwan. The study population included 912 workers without hypertension at baseline. The outcome of interest was the development of hypertension during the study period. The studied determinants were three AGT genotypes (TT, TM and MM) and four exposure categories according to the levels of noise representing high (>80 dBA), medium (80-65 dBA), low exposure (64-50 dBA) and the reference level (49-40 dBA). In Poisson regression adjusting for confounders, AGT (TT vs MM adjusted incidence rate ratio (IRR) 1.77, 95% CI 1.24 to 2.51) and noise exposure (high and medium combined) during 3-15 years (adjusted IRR 2.35, 95% CI 1.42 to 3.88) were independent determinants of hypertension. Furthermore, the risk of hypertension increased with noise exposure (adjusted IRR 3.73, 95% CI 1.84 to 7.56) among TT homozygotes but not among those with at least one M allele (Rothman synergy index=1.05). The results evidence further the independent effects of AGT gene polymorphisms and exposure to occupational noise. Our finding also suggests that workers carrying TT variant allele have higher risk of hypertension under chronic exposure to occupational noise.

  12. 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

  13. Uptake of ascorbic acid by pancreatic acinar cells is negatively impacted by chronic alcohol exposure.

    PubMed

    Subramanian, Veedamali S; Srinivasan, Padmanabhan; Said, Hamid M

    2016-07-01

    Vitamin C (ascorbic acid, AA) is indispensable for normal metabolism of all mammalian cells including pancreatic acinar cells (PACs). PACs obtain AA from their surroundings via transport across the cell membrane. Chronic alcohol exposure negatively affects body AA homeostasis; it also inhibits uptake of other micronutrients into PACs, but its effect on AA uptake is not clear. We examined this issue using both in vitro (266-6 cells) and in vivo (mice) models of chronic alcohol exposure. First, we determined the relative expression of the AA transporters 1 and 2 [i.e., sodium-dependent vitamin C transporter-1 (SVCT-1) and SVCT-2] in mouse and human PACs and found SVCT-2 to be the predominant transporter. Chronic exposure of 266-6 cells to alcohol significantly inhibited AA uptake and caused a marked reduction in SVCT-2 expression at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Similarly, chronic alcohol feeding of mice significantly inhibited AA uptake and caused a marked reduction in level of expression of the SVCT-2 protein, mRNA, and hnRNA. These findings suggest possible involvement of transcriptional mechanism(s) in mediating chronic alcohol effect on AA uptake by PACs. We also observed significant epigenetic changes (histone modifications) in the Slc23a2 gene (reduction in H3K4me3 level and an increase in H3K27me3 level) in the alcohol-exposed 266-6 cells. These findings show that chronic alcohol exposure inhibits PAC AA uptake and that the effect is mediated, in part, at the level of transcription of the Slc23a2 gene and may involve epigenetic mechanism(s).

  14. 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...

  15. 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...

  16. Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort†

    PubMed Central

    Mathews, Carol A.; Scharf, Jeremiah M.; Miller, Laura L.; Macdonald-Wallis, Corrie; Lawlor, Debbie A.; Ben-Shlomo, Yoav

    2014-01-01

    Background Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. Aims To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort. Method Relationships between exposures and Tourette syndrome/chronic tic disorder were examined in 6090 children using logistic regression. Results Maternal alcohol and cannabis use, inadequate maternal weight gain and parity were associated with Tourette syndrome or Tourette syndrome/chronic tic disorder. Other previously reported exposures, including birth weight and prenatal maternal smoking, were not associated with Tourette syndrome/chronic tic disorder. Conclusions This study supports previously reported relationships between Tourette syndrome/chronic tic disorder and prenatal alcohol exposure, and identifies additional previously unexplored potential prenatal risk factors. PMID:24262815

  17. Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort.

    PubMed

    Mathews, Carol A; Scharf, Jeremiah M; Miller, Laura L; Macdonald-Wallis, Corrie; Lawlor, Debbie A; Ben-Shlomo, Yoav

    2014-01-01

    Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort. Relationships between exposures and Tourette syndrome/chronic tic disorder were examined in 6090 children using logistic regression. Maternal alcohol and cannabis use, inadequate maternal weight gain and parity were associated with Tourette syndrome or Tourette syndrome/chronic tic disorder. Other previously reported exposures, including birth weight and prenatal maternal smoking, were not associated with Tourette syndrome/chronic tic disorder. This study supports previously reported relationships between Tourette syndrome/chronic tic disorder and prenatal alcohol exposure, and identifies additional previously unexplored potential prenatal risk factors.

  18. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms

    PubMed Central

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati

    2014-01-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5′-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na+ dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms. PMID:25214397

  19. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    PubMed

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms. Copyright © 2014 the American Physiological Society.

  20. Effect of chronic alcohol exposure on folate uptake by liver mitochondria.

    PubMed

    Biswas, Arundhati; Senthilkumar, Sundar Rajan; Said, Hamid M

    2012-01-01

    Mammalian cells obtain folate, a water-soluble vitamin, from their surroundings via transport across cell membrane. Intracellular folate is compartmentalized between the cytoplasm and the mitochondria. Transport of folate from the cytoplasm into the mitochondria is via a specific carrier-mediated process involving the mitochondrial folate transporter (MFT). Chronic alcohol use negatively impacts folate homeostasis, but its effect on mitochondrial folate uptake is not clear. We addressed this issue using mitochondrial preparations isolated from the liver of rats chronically fed an alcohol liquid diet and from human liver HepG2 cells chronically exposed to alcohol. The results showed that chronic alcohol feeding of rats leads to a significant inhibition in mitochondrial carrier-mediated folate uptake. This inhibition was associated with a significant reduction in the level of expression of the MFT protein, mRNA, and heterogenous nuclear RNA (hnRNA). Similarly, chronic alcohol exposure (96 h) of HepG2 cells led to significant inhibition in mitochondrial carrier-mediated folate uptake, which was associated with a marked reduction in the level of expression of the human MFT (hMFT). To determine whether the latter effect is, in part, being exerted at the transcriptional level, we cloned the 5'-regulatory region of the human SLC25A32 gene (which encodes the hMFT) and showed that chronic alcohol exposure of HepG2 cells leads to a significant inhibition in its promoter activity. These studies show for the first time that chronic alcohol feeding/exposure leads to a significant inhibition in mitochondrial carrier-mediated folate uptake and that the inhibition is, in part, being exerted at the level of transcription of the SLC25A32 gene.

  1. Damage to rat spermatozoal DNA after chronic cyclophosphamide exposure.

    PubMed

    Qiu, J; Hales, B F; Robaire, B

    1995-12-01

    Treatment of male rats with low dosages of cyclophosphamide causes a dramatic increase in early embryo death among their progeny without significantly affecting the general health of the male. It is hypothesized that cyclophosphamide exerts its effects by targeting specific components of spermatozoal nuclei. The purpose of the present studies was to investigate the effects of chronic cyclophosphamide treatment on spermatozoal DNA. Two approaches were pursued. The first was to determine total DNA damage by using the alkaline elution method. The second was to study spermatozoal DNA template function by using an in vitro DNA synthesis system. Adult male rats were treated with saline or cyclophosphamide (6.1 mg/kg/day) daily for 1 or 6 wk. Cauda epididymal spermatozoa were collected and subjected to alkaline elution using DNA-DNA dot hybridization to quantify the fractionated DNA. One week of treatment with cyclophosphamide caused DNA single strand breaks that could be detected only in the presence of proteinase K in the lysis solution; no DNA cross-links were observed in the animals that received 1-wk drug treatment. In contrast, 6 wk of treatment with cyclophosphamide induced a significant increase in both DNA single strand breaks and cross-links in spermatozoal nuclei; the cross-links were attributable primarily to DNA-DNA linkages. The availability of spermatozoal DNA for template function was not affected by 1 wk of treatment with cyclophosphamide but was markedly affected after 6 wk of treatment with this drug. It is proposed that during chromatin transition processes the male genome may be in an open dynamic state with many exposed sites that are vulnerable to alkylating agents. Since there is no DNA repair during spermiogenesis, damage to the genome by alkylation at this stage may be cumulative, resulting in the production of dysfunctional germ cells.

  2. Chronic exposures to monomethyl phthalate in Western clawed frogs.

    PubMed

    Mathieu-Denoncourt, Justine; de Solla, Shane R; Langlois, Valerie S

    2015-08-01

    Polymer flexibility and elasticity is enhanced by plasticizers. However, plasticizers are often not covalently bound to plastics and thus can leach from products into the environment. Much research effort has focused on their effects in mammalian species, but data on aquatic species are scarce. In this study, Western clawed frog (Silurana tropicalis) embryos were exposed to 1.3, 12.3, and 128.7mg/L monomethyl phthalate (MMP) until the juvenile stage (11weeks) and to 1.3mg/L MMP until the adult stage (51weeks). MMP decreased survival, hastened metamorphosis, and biased the sex ratio toward males (2M:1F) at the juvenile stage without altering the expression of a subset of thyroid hormone-, sex steroid-, cellular stress- or transcription regulation-related genes in the juvenile frog livers. At the adult stage, exposure to MMP did not have significant adverse health effects, except that females had larger interocular distance and the expression of the heat shock protein 70 was decreased by 60% in the adult liver. In conclusion, this study shows that MMP is unlikely to threaten amphibian populations as only concentrations four orders of magnitude higher than the reported environmental concentrations altered the animal physiology. This is the first complete investigation of the effects of phthalates in a frog species, encompassing the entire life cycle of the organisms. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  3. Effects of continuous and pulsed chronic microwave exposure on rabbits

    NASA Astrophysics Data System (ADS)

    Chou, Chung-Kwang; Guy, Arthur W.; McDougall, John A.; Han, Lock-Fong

    1982-01-01

    Eighteen young adult New Zealand rabbits (nine males, nine females) were equally divided into three groups. One group was exposed to CW 2450-MHz fields at an incident power density of 1.5 mW/cm2 for 2 hours daily for 3 months. Another group was exposed to pulsed fields with pulses of 10 μ s duration occurring 100 times per second. The third group was sham exposed. Each rabbit was placed in a Plexiglas cage and exposed in a miniature plane wave exposure chamber. An S band horn was mounted 1 m above the animal. Thermographic data showed a peak specific absorption rate of 1.64 W/kg in the head and 2.1 W/kg in the back. Body weights were measured every other day. Electroencephalogram and evoked potentials were recorded weekly via implanted carbon-loaded Teflon electrodes. Blood samples were taken monthly for hematological, chemical, and morphological studies. Eyes were examined for cataract formation. Before the animals were sacrificed, apomorphine-induced behavioral excitation and hyperthermia were studied. Finally, pathological examinations on many tissues and organs were performed. Statistically, there were no significant differences in measured parameters observed between the exposed and sham animals.

  4. 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.

  5. Characterisation of cochlear inflammation in mice following acute and chronic noise exposure.

    PubMed

    Tan, Winston J T; Thorne, Peter R; Vlajkovic, Srdjan M

    2016-08-01

    Oxidative stress has been established as the key mechanism of the cochlear damage underlying noise-induced hearing loss, however, emerging evidence suggests that cochlear inflammation may also be a major contributor. This study aimed to improve our understanding of the cochlear inflammatory response associated with acute and chronic noise exposure. C57BL/6 mice were exposed to acute traumatic noise (100 dBSPL, 8-16 kHz for 24 h) and their cochleae collected at various intervals thereafter, up to 7 days. Using quantitative RT-PCR and immunohistochemistry, changes in expression levels of proinflammatory cytokines (TNF-α, IL-1β), chemokines (CCL2) and cell adhesion molecules (ICAM-1) were studied. All gene transcripts displayed similar dynamics of expression, with an early upregulation at 6 h post-exposure, followed by a second peak at 7 days. ICAM-1 immunoexpression increased significantly in the inferior region of the spiral ligament, peaking 24 h post-exposure. The early expression of proinflammatory mediators likely mediates the recruitment and extravasation of inflammatory cells into the noise-exposed cochlea. The occurrence of the latter expression peak is not clear, but it may be associated with reparative processes initiated in response to cochlear damage. Chronic exposure to moderate noise (90 dBSPL, 8-16 kHz, 2 h/day, up to 4 weeks) also elicited an inflammatory response, reaching a maximum after 2 weeks, suggesting that cochlear damage and hearing loss associated with chronic environmental noise exposure may be linked to inflammatory processes in the cochlea. This study thus provides further insight into the dynamics of the cochlear inflammatory response induced by exposure to acute and chronic noise.

  6. 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).

  7. Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers

    PubMed Central

    Rushton, L; Schnatter, A R; Tang, G; Glass, D C

    2014-01-01

    Background: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case–control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL). Methods: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines. Results: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers. Conclusion: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone. PMID:24357793

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

    PubMed Central

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

    2010-01-01

    Background 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 the present 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. Methods 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), non-manipulated/acutely challenged with ethanol (4 g/kg on day 10) or non-manipulated. For assessment of tolerance development, loss of righting reflex was tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and non-manipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hrs after the last ethanol exposure, with ethanol-naïve chronic saline and non-manipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and non-manipulated animals using an 8 day 2 bottle choice, limited access ethanol intake procedure. Results Adolescents were less sensitive to the sedative effects of ethanol than adults. 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 g/kg basis, with intake uninfluenced by prior ethanol exposure at both ages. Conclusion Adolescents and adults may differ in

  9. 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

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

    PubMed

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

    2015-11-16

    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.

  11. Chronic, low concentration exposure to pharmaceuticals impacts multiple organ systems in zebrafish.

    PubMed

    Galus, Michal; Kirischian, Nina; Higgins, Sarah; Purdy, James; Chow, Justin; Rangaranjan, Sahaana; Li, Hongxia; Metcalfe, Chris; Wilson, Joanna Y

    2013-05-15

    Pharmaceuticals are found in both receiving and drinking water due to their persistent release in waste-water effluents, raising concerns for environmental and human health. Chronic, aqueous exposure of zebrafish (Danio rerio) to environmentally relevant concentrations of acetaminophen (ACE), venlafaxaine (VEN) (10μgL(-1)), carbamazepine (CBZ) and gemfibrozil (GEM) (0.5 and 10μgL(-1)) decreased reproductive output. Atretic oocytes and altered ovarian histology were seen in female zebrafish exposed to CBZ and GEM, suggesting a direct effect on oocyte development that may account for the reduced fecundity. Apoptosis within the theca and granulosa cells was identified in exposed female zebrafish with atretic oocytes by TUNEL positive staining. The incidence of follicular apoptosis was nearly 2-fold higher in exposed females than the controls. All compounds significantly altered kidney proximal tubule morphology but there was no difference in the incidence of apoptotic cells within the kidney between control and exposed in either males or females. Liver histology was altered by ACE and GEM exposure. Parental exposure to pharmaceuticals did not increase developmental abnormalities, hatching success, or mortality in embryos. Yet, direct exposure of embryos to ACE increased developmental abnormalities and mortality; exposure to 0.5μgL(-1) of all pharmaceuticals increased mortality. CBZ decreased plasma 11-ketotestosterone concentrations in males and females. Overall, these data suggest that low concentration, chronic exposure of fish to pharmaceuticals impacts fish development as well as multiple organ systems in adult fish, leading to effects on reproduction and histology of liver and kidney. These results are significant in understanding the consequences of chronic, low concentration pharmaceutical exposure to fish and suggest that exposed populations are at risk of negative impacts to reproduction and health. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Investigating the impact of chronic atrazine exposure on sexual development in zebrafish

    PubMed Central

    Corvi, Margaret M; Stanley, Kerri A; Peterson, Peterson; Kent, Michael L; Feist, Stephen W; La Du, Jane K; Volz, David C; Hosmer, Hosmer; Tanguay, Robert L

    2014-01-01

    Atrazine (ATZ) is a selective triazine herbicide used primarily for pre-emergent weed control in corn, sorghum and sugar cane production. It is one of the most widely used herbicides in North America. Some research published over the last decade suggests that chronic exposure to environmentally relevant ATZ concentrations can adversely impact gonadal development and/or sexual differentiation in amphibians and fish, while other studies report no effect, or moderate effects. As a result, contrasting conclusions have been published regarding the potential effects of the herbicide ATZ on aquatic species. Two near-identical four-month studies in 2009 (Study I) and 2010 (Study II), were performed investigating the potential for chronic ATZ exposure to affect zebrafish (Danio rerio) sexual development and differentiation. Zebrafish, were chronically exposed to 0, 0.1, 1, 10 µM ATZ or 1 nM 17α-estradiol (E2). Fish were histologically examined to assign gender and to evaluate potential impacts of E2 or ATZ on gonadal development. Exposure to E2 consistently resulted in a significantly higher proportion of female fish to normal male fish when compared to unexposed fish (both studies). In both studies, ATZ exposure did not significantly influence the percentage of female or male fish when compared to unexposed fish. A greater percentage of abnormally developed male fish and fish lacking differentiated gonadal tissue was observed in Study II E2 exposures but not in ATZ exposures. Together, these studies indicate that long-term exposure to ATZ at or above environmentally relevant concentrations does not significantly impact zebrafish gonadal development or sexual differentiation. PMID:22581590

  13. Chronic drug exposures during development in nonhuman primates: models of brain dysfunction in humans.

    PubMed

    Paule, Merle G

    2005-09-01

    This review of our work presents three specific examples of how nonhuman primates (rhesus monkeys, Macaca mulatta) have been used to study the effects of chronic drug exposures on brain function during different stages of development. In all cases, exposure levels similar to those experienced by humans were employed and the focus was on long-term--not acute--effects. In the case of the marijuana studies, exposures occurred during the adolescent period; for the cocaine studies, exposures occurred in binge-like fashion entirely before birth (in utero); and for the remacemide studies, exposures occurred daily in juveniles, prior to adolescence. An automated battery of behavioral tasks, the National Center for Toxicological Research Operant Test Battery (NCTR OTB), designed to assess aspects of motivation, visual discrimination, time perception, short-term memory, and learning, was used to monitor treatment effects. Chronic marijuana smoke exposure resulted in an 'amotivational' syndrome--even in weekend-only smokers--that resolved within three months of exposure cessation. In utero cocaine exposure was shown to cause behavioral rigidity or lack of plasticity as evidenced by the difficulty of subjects to adjust to rules changes for some OTB tasks. These effects were seen in adult subjects suggesting that the effects of gestational cocaine exposure are long-term or permanent. In addition, animals exposed to cocaine in utero were less sensitive to the behaviorally-disrupting effects of cocaine as adults. Remacemide caused profound and long-lasting, perhaps permanent, changes in learning task performance and because performance of this same task by children is significantly correlated with traditional measures of intelligence (IQ), these data suggest that such treatment may provide a valuable model of chemically-induced mental retardation.

  14. Chronic perchlorate exposure impairs stickleback reproductive behaviour and swimming performance

    PubMed Central

    Bernhardt, Richard R.; von Hippel, Frank A.

    2011-01-01

    Summary We describe behavioural changes in two generations of threespine stickleback (Gasterosteus aculeatus) exposed to environmentally relevant concentrations of perchlorate. The first generation (G0,2002) was exposed as two-year-old adults to perchlorate in experimental groups ranging in concentration from less than the method detection limit (<1.1 ppb) to 18.6 ppm for up to 22 days during their courtship, spawning, egg guarding, and first five days of fry guarding. No differences were noted in the behaviour or reproductive output of these fish that were exposed as adults. However, perchlorate exposure throughout development caused widespread effects in the second generation (G1,2003), which was spawned and raised through sexual maturity in one of four nominal experimental groups (0, 30 and 100 ppm, and a ‘variable’ treatment that progressively increased from <1.1 ppb to approximately 60 ppm perchlorate). Dose-dependent effects were found during the G1,2003’s swimming and behavioural evaluations, including higher mortality rates among treated fish following stressful events. Perchlorate-exposed fish had higher failure rates during swimming trials and failed at lower flow rates than control fish. A number of treated fish exhibited seizures. Progressively fewer males completed benchmark metrics, such as nest building, spawning, nursery formation, or fry production, in a dose-dependent manner. Fewer males from higher treatments courted females, and those that did initiated courtship later and had a reduced behavioural repertoire compared to fish from lower treatments. The lowest observed adverse effect level (LOAEL) for swimming performance, reproductive behaviour, survivorship and recruitment was 30 ppm perchlorate (our lowest G1,2003 treatment), and near complete inhibition of reproductive activity was noted among males raised in 100 ppm perchlorate. A small number of treated G1,2003 females were isolated in aquaria, and some performed reproductive

  15. Passive smoke exposure in chronic rhinosinusitis as assessed by hair nicotine

    PubMed Central

    Wentzel, Jennifer L.; Soler, Zachary M.; White, David R.; Schlosser, Rodney J.

    2014-01-01

    Background: Prevalence of passive smoke exposure is relatively unknown in chronic rhinosinusitis (CRS). Previous studies have attempted to establish this relationship using subjective, questionnaire-based methodologies to assess smoke exposure, thus introducing the potential for error bias. The purpose of this study was to accurately determine the prevalence of passive smoke exposure in CRS and control patients using hair nicotine levels as a quantitative measure of cigarette smoke exposure. Methods: Hair samples were obtained at time of surgery from 569 patients: 404 undergoing surgery for CRS and 165 controls undergoing surgery for repair of cerebrospinal fluid leak, removal of pituitary tumors, or adenoidectomy from 2007 to 2013. Patient charts were reviewed for reported smoking status. Hair nicotine was quantified using reversed-phase high-performance liquid chromatography. Nonsmoking patients were classified as passive smoke exposed or smoke naïve according to the hair nicotine results. Statistical analysis was performed to test for differences in demographic information and smoke exposure prevalence between CRS, CRS subtypes, and controls. Results: The prevalence of passive smoke exposure in CRS as documented by hair nicotine was lower than previously reported subjective estimates. Passive smoke exposure rates were equivalent between those with CRS versus controls and significantly higher in children. Severity of passive smoke exposure was also equivalent between CRS subsets and controls. Annual passive smoke exposure prevalence did not change over time. Conclusion: There is no clear evidence of avoidance of passive smoke exposure in the CRS population compared with controls. Passive smoke exposure also remained stable over time despite recent regional implementation of smoking bans. Given the constancy of exposure, it is critical that the impact of passive smoke on CRS exacerbation, outcomes, and pathophysiology be evaluated in large-scale clinical studies

  16. Effects of chronic low level lead exposure on the physiology of individually identifiable neurons.

    PubMed

    Audesirk, G; Audesirk, T

    1983-01-01

    Although chronic exposure to lead has been correlated with a variety of behavioral and neurochemical deficits in humans and other mammals, little is known of the mechanisms of action of chronic lead at the level of the individual nerve cell. We have used the individually identifiable neurons of the freshwater pond snail Lymnaea stagnalis as a model system to investigate the effects of chronic low level (5 microM) lead exposure on neuronal physiology. Thirteen neuronal parameters were measured with intracellular microelectrode recording in each of six different identifiable neurons or homogeneous neuron clusters. Results were analyzed by a multivariate analysis of variance (MANOVA). MANOVA analysis indicates that there is a significant overall effect of lead exposure (p = 0.0001) and a significant interaction between lead and neuron type (p = 0.01). In most neuron types, chronic lead causes an increase in the resting potential, a slowing of recovery of the membrane potential after the undershoot of a spike, a decrease in spontaneous spiking activity, and a decrease in the input resistance. Lead also has differential effects on identifiable neurons, depressing excitability in some neuron types while not altering excitability in others.

  17. [Management of hypothermia -- Severe Accidental Hypothermia Centre in Krakow].

    PubMed

    Darocha, Tomasz; Kosiński, Sylweriusz; Jarosz, Anna; Sobczyk, Dorota; Gałązkowski, Robert; Sanak, Tomasz; Hymczak, Hubert; Kapelak, Bogusław; Drwiła, Rafał

    2015-01-01

    Severe accidental hypothermia is a condition associated with significant morbidity and mortality. In the years 2009–2012 the Polish National Statistics Department reported 1836 deaths due to exposure to excessive natural cold. The Severe Accidental Hypothermia Centre (CLHG, Centrum Leczenia Hipotermii Glebokiej) was set up in Krakow in 2013. It is a unit functioning within the structure of the Cardiac Surgery Clinic, established in order to improve the effectiveness of the treatment of patients in the advanced stages of severe hypothermia. Early identification of hypothermia, binding algorithm and coordination leading to extracorporeal rewarming, are the most important elements in the deep hypothermia management.

  18. Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: mechanisms and reversal by exogenous ACTH.

    PubMed

    Boyd, Kevin N; Kumar, Sandeep; O'Buckley, Todd K; Morrow, A Leslie

    2010-10-01

    Acute ethanol administration increases potent GABAergic neuroactive steroids, specifically (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP) and (3α,5α)-3,21-dihydroxypregnan-20-one. In addition, neuroactive steroids contribute to ethanol actions. Chronic ethanol exposure results in tolerance to many effects of ethanol, including ethanol-induced increases in neuroactive steroid levels. To determine the mechanisms of tolerance to ethanol-induced increases in neuroactive steroids, we investigated critical signaling molecules that are required for acute ethanol effects. Male Sprague-Dawley rats were administered ethanol via liquid diet for 2 weeks and steroid levels, adrenocorticotrophic hormone (ACTH) and adrenal steroidogenic acute regulatory (StAR) protein expression were measured. Chronic ethanol exposure elicits tolerance to ethanol-induced elevation of serum ACTH and the steroids pregnenolone and progesterone. Surprisingly, chronic ethanol exposure does not result in tolerance to ethanol-induced increases in adrenal StAR protein. However, ethanol-induced StAR phosphorylation is decreased when compared to acute ethanol administration. A separate group of rats exposed to chronic ethanol diet were subsequently challenged with ethanol (2 g/kg) and exhibited a blunted elevation of serum ACTH and progesterone as well as cerebral cortical and hippocampal 3α,5α-THP. Administration of ACTH with the ethanol challenge restored the elevation of serum ACTH and progesterone as well as cerebral cortical 3α,5α-THP levels to those observed in ethanol-naïve rats. Thus, chronic ethanol exposure disrupts ACTH release, which results in tolerance to ethanol-induced increases in neuroactive steroid levels. Loss of the ethanol-induced increases in neuroactive steroids may contribute to behavioral tolerance to ethanol and influence the progression towards alcoholism. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

  19. 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...

  20. 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...

  1. [Accidental mercury poisoning in a 12-year-old girl].

    PubMed

    Alby-Laurent, F; Honoré-Goldman, N; Cavau, A; Bellon, N; Allali, S; Abadie, V

    2016-11-01

    Exposure to metallic mercury can cause severe accidental intoxications in children, whose clinical symptoms can vary depending on the route of administration, the dose, as well as the time and duration of the exposure. It has become unusual in France, yet it must be considered when taking a patient's medical history in cases of multisystemic involvement without a clear explanation. We report the case of a 12-year-old patient hospitalized because of a cough, poor general condition, chills, night sweats, psychomotor retardation, and skin lesions that had been developing for several weeks. The initial clinical examination also revealed sinus tachycardia, arterial hypertension, and abolition of osteotendinous reflexes. Complementary examination results were normal apart from a glomerular proteinuria without renal failure. When interviewing the mother, she reported that the child had played with mercury balls 3 months earlier. The suspicion of poisoning was confirmed by blood and urine analysis as well as renal biopsy showing an aspect of membranous glomerulonephritis with IgG and C3 depositions. An intoxication via a transdermal route being unlikely on healthy skin, the Regional Health Agency's survey concluded that chronic intoxication had occurred by inhalation of the mercury spread on the floor at the time of the exposure, which was then vacuum cleaned and released again by the contaminated vacuum cleaner. The patient's outcome was favorable within a few weeks after initiating DMSA chelation therapy. Mercury poisoning should be considered in cases of a multisystemic disorder without clear explanation, in order to intervene quickly and thus prevent irreversible renal and neurological consequences. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Investigation of rare chronic lipoid pneumonia associated with occupational exposure to paraffin aerosol.

    PubMed

    Han, Chenghong; Liu, Lihai; Du, Shiping; Mei, Jianhua; Huang, Ling; Chen, Min; Lei, Yongliang; Qian, Junwen; Luo, Jianyong; Zhang, Meibian

    2016-09-30

    Occupational exposure to paraffin is an infrequent cause of lipoid pneumonia (LP) and related data are scare. We investigated the possible relationship between three rare cases of chronic LP and occupational exposure to paraffin aerosol in an iron foundry. The three cases of LP and their workplaces were investigated using data from field investigations, air monitoring, pulmonary radiological examinations, cell staining, and lung biopsies. The patients had long-term occupational exposure to paraffin. X-ray diffraction testing revealed that the raw material from the workshop was paraffin crystal. The air concentrations of paraffin aerosol in workplaces were significantly higher than outdoor background levels. Small diffuse and miliary shadows with unclear edges were observed throughout the whole lungs via radiography. Computed tomography revealed diffuse punctate nodules and a high density of stripe-like shadows in both lungs (ground-glass opacity in a lower lobe, and a mass-like lesion and high translucent area near the bottom of the lung). Lipid-laden macrophages were found in the sputum and bronchial lavage. A broadened alveolar septum and local focal fibrosis were also discovered via lung biopsy. The inflammatory reaction in the lung tissues appeared to resolve over time. These three rare cases of chronic LP in workers during molding and repair processes were associated with occupational paraffin aerosol exposure. Therefore, primary prevention is essential for molding or repairing workers in the iron foundry, and a differential diagnosis of occupational chronic LP (vs. pneumoconiosis) should be considered when treating these workers.

  3. Cancer Events After Acute or Chronic Exposure to Sulfur Mustard: A Review of the Literature

    PubMed Central

    Razavi, Seyed Mansour; Abdollahi, Mohammad; Salamati, Payman

    2016-01-01

    Background: Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings. Methods: The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed. Results: Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma. Conclusions: SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure. PMID:27280012

  4. 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.

  5. Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake.

    PubMed

    Srinivasan, Padmanabhan; Subramanian, Veedamali S; Said, Hamid M

    2014-04-01

    Pancreatic acinar cells (PAC) obtain thiamin from the circulation via a carrier-mediated process that involves thiamin transporters 1 and 2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3, respectively). Chronic alcohol exposure of PAC inhibits thiamin uptake, and, on the basis of in vitro studies, this inhibition appears to be transcriptionally mediated. The aim of this study was to confirm the involvement of a transcriptional mechanism in mediating the chronic alcohol effect in in vivo settings and to delineate the molecular mechanisms involved. Using transgenic mice carrying full-length SLC19A2 and SLC19A3 promoters, we found that chronic alcohol feeding led to a significant reduction in the activity of SLC19A2 and SLC19A3 promoters (as well as in thiamin uptake and expression of THTR-1 and -2). Similar findings were seen in 266-6 cells chronically exposed to alcohol in vitro. In the latter studies, the alcohol inhibitory effect was found to be mediated via the minimal SLC19A2 and SLC19A3 promoters and involved the cis-regulatory elements stimulating protein 1 (SP1)/gut-enriched Kruppel-like factor and SP1-GG-box and SP1/GC, respectively. Chronic alcohol exposure of PAC also led to a significant reduction in the expression of the SP1 transcription factor, which upon correction (via expression) led to the prevention of alcohol inhibitory effects on not only the activity of SLC19A2 and SLC19A3 promoters but also on the expression of THTR-1 and -2 mRNA and thiamin uptake. These results demonstrate that the inhibitory effect of chronic alcohol exposure on physiological/molecular parameters of thiamin uptake by PAC is mediated via specific cis-regulatory elements in SLC19A2 and SLC19A3 minimal promoters.

  6. Acute and chronic cadmium exposure promotes E-cadherin degradation in MCF7 breast cancer cells.

    PubMed

    Ponce, Esmeralda; Louie, Maggie C; Sevigny, Mary B

    2015-10-01

    Cadmium is an environmental carcinogen that usually enters the body at minute concentrations through diet or cigarette smoke and bioaccumulates in soft tissues. In past studies, cadmium has been shown to contribute to the development of more aggressive cancer phenotypes including increased cell migration and invasion. This study aims to determine if cadmium exposure-both acute and chronic-contributes to breast cancer progression by interfering with the normal functional relationship between E-cadherin and β-catenin. An MCF7 breast cancer cell line (MCF7-Cd) chronically exposed to 10(-7)  M CdCl2 was previously developed and used as a model system to study chronic exposures, whereas parental MCF7 cells exposed to 10(-6)  M CdCl2 for short periods of time were used to study acute exposures. Cadmium exposure of MCF7 cells led to the degradation of the E-cadherin protein via the ubiquitination pathway. This resulted in fewer E-cadherin/β-catenin complexes and the relocation of active β-catenin to the nucleus, where it interacted with transcription factor TCF-4 to modulate gene expression. Interestingly, only cells chronically exposed to cadmium showed a significant decrease in the localization of β-catenin to the plasma membrane and an increased distance between cells. Our data suggest that cadmium exposure promotes breast cancer progression by (1) down-regulating E-cadherin, thus decreasing the number of E-cadherin/β-catenin adhesion complexes, and (2) enhancing the nuclear translocation of β-catenin to increase expression of cancer-promoting proteins (i.e., c-Jun and cyclin D1).

  7. Sensitization and chronic beryllium disease at a primary manufacturing facility, part 1: historical exposure reconstruction.

    PubMed

    Virji, M Abbas; Park, Ji Young; Stefaniak, Aleksandr B; Stanton, Marcia L; Day, Gregory A; Kent, Michael S; Kreiss, Kathleen; Schuler, Christine R

    2012-05-01

    Previous epidemiologic studies of beryllium sensitization (BeS) and chronic beryllium disease (CBD) have reported inconsistent exposure-response relationships, likely due to exposure misclassification. The objective of this study was to develop historical estimates of size-selective personal exposure to beryllium for an epidemiologic study. In 1999, a cross-sectional survey of workers hired after 1 January 1994 was conducted at a beryllium production facility. Personal exposure data from two air sampling surveys conducted in 1999 were used to obtain total, respirable, and submicron particle baseline exposure estimates (BEE) for a job-exposure matrix (JEM). General area air samples collected from 1994-1999 were used to estimate annual changes in exposures (temporal factors) for 24 different process areas. Historical exposure estimates (HEE) were calculated by applying the temporal factors to the BEE. Workers were assigned HEE based on their work history, and their historical exposure profile was summarized as cumulative, average, or highest-ever job exposure. Changes in exposure over a 6-year period were observed in 10 of the 24 process areas with an overall mean decline of 18% per year. The overall total exposure for study participants over their work tenure ranged from: 0.001-34.44 μg/m(3)-year, 0.01-16.26 μg/m(3), and 0.01-17.54 μg /m(3) for cumulative, average, and highest-ever job, respectively. For respirable exposures, the ranges were: 0.001-15.54 μg/m(3)-year, 0.01-3.56 μg/m(3), 0.01-5.54 μg /m(3) for cumulative, average, and highest-ever job, respectively. Using this JEM, exposure-response relationships for BeS and CBD can be explored over a range of exposure metrics such as total, respirable, and submicron beryllium mass concentrations, including summary measures such as cumulative, average, or highest exposures, with the ultimate objective of elucidating a quantitative exposure-response relationship.

  8. Chronic exposure to water-pipe smoke induces cardiovascular dysfunction in mice.

    PubMed

    Nemmar, Abderrahim; Al-Salam, Suhail; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Ali, Badreldin H

    2017-02-01

    Water-pipe tobacco smoking is becoming prevalent in all over the world including Western countries. There are limited data on the cardiovascular effects of water-pipe smoke (WPS), in particular following chronic exposure. Here, we assessed the chronic cardiovascular effects of nose-only WPS exposure in C57BL/6 mice. The duration of the session was 30 minutes/day, 5 days/week for 6 consecutive months. Control mice were exposed to air. WPS significantly increased systolic blood pressure. The relative heart weight and plasma concentrations of troponin-I and B-type natriuretic peptide were increased in mice exposed to WPS. Arterial blood gas analysis showed that WPS caused a significant decrease in [Formula: see text] and an increase in [Formula: see text] WPS significantly shortened the thrombotic occlusion time in pial arterioles and venules and increased the number of circulating platelet. Cardiac lipid peroxidation, measured as thiobarbituric acid-reactive substances, was significantly increased, while superoxide dismutase activity, total nitric oxide activity, and glutathione concentration were reduced by WPS exposure. Likewise, immunohistochemical analysis of the heart revealed an increase in the expression of inducible nitric oxide synthase and cytochrome c by cardiomyocytes of WPS-exposed mice. Moreover, hearts of WPS-exposed mice showed the presence of focal interstitial fibrosis. WPS exposure significantly increased heart DNA damage assessed by Comet assay. We conclude that chronic nose-only exposure to WPS impairs cardiovascular homeostasis. Our findings provide evidence that long-term exposure to WPS is harmful to the cardiovascular system and supports interventions to control the spread of WPS, particularly amid youths.NEW & NOTEWORTHY No data are available on the chronic cardiovascular effects of water-pipe smoke (WPS). Our findings provide experimental evidence that chronic exposure to WPS increased blood pressure, relative heart weight, troponin I, and

  9. Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease.

    PubMed

    Paulin, Laura M; Diette, Gregory B; Blanc, Paul D; Putcha, Nirupama; Eisner, Mark D; Kanner, Richard E; Belli, Andrew J; Christenson, Stephanie; Tashkin, Donald P; Han, MeiLan; Barr, R Graham; Hansel, Nadia N

    2015-03-01

    Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. To determine the impact of occupational exposures on COPD morbidity. A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

  10. Effects of chronic dietary copper exposure on growth and reproduction of Daphnia magna.

    PubMed

    De Schamphelaere, Karel A C; Janssen, Colin R

    2004-08-01

    A matter of current, intense debate with regard to the effects of metals on biological systems is the potential toxicity of metals associated with food particles. Recently developed biotic ligand models (BLM), which predict the toxicity of waterborne metals, may not be valid if the dietary exposure route contributes to metal toxicity. The present study is, to our knowledge, the first that investigates the potential toxicity of dietary copper to a freshwater invertebrate (i.e., Daphnia magna) feeding on a live diet (i.e., the green alga Pseudokircheneriella subcapitata). Algae were exposed for 3 d to different copper concentrations, resulting in algal copper burdens between approximately 6.2 X 10(-16) and 250 x 10(-16) g cell(-1). These algae were then used as food in chronic, 21-d D. magna toxicity tests in which growth, reproduction, and copper accumulation were assessed. Three exposure scenarios were tested: A waterborne exposure, a dietary exposure, and a combined waterborne and dietary exposure. Although exposure to dietary copper resulted in an increased copper body burden of the adult daphnids, it did not contribute to toxicity and did not affect the 21-d effect concentrations expressed as waterborne copper, indicating that the previously established good predictive capacity of the chronic D. magna BLM is not affected. On the contrary, exposure to the highest dietary copper levels resulted in an increase of as much as 75% in growth and reproduction. To our knowledge, this is the first evidence that dietary copper exposure of a freshwater invertebrate feeding on a live diet resulted in a beneficial effect.

  11. Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process

    PubMed Central

    Subramanian, Veedamali S.; Subramanya, Sandeep B.

    2011-01-01

    Normal body homeostasis of biotin is critically dependent on its renal recovery by kidney proximal tubular epithelial cells, a process that is mediated by the sodium-dependent multivitamin transporter (SMVT; a product of the SLC5A6 gene). Chronic ethanol consumption interferes with the renal reabsorption process of a variety of nutrients, including water-soluble vitamins. To date, however, there is nothing known about the effect of chronic alcohol feeding on physiological and molecular parameters of the renal biotin reabsorption process. We addressed these issues using rats and transgenic mice carrying the human SLC5A6 (P1P2) 5′-regulatory region as an in vivo model systems of alcohol exposure, and cultured human renal proximal tubular epithelial HK-2 cells chronically exposed to alcohol as an in vitro model of alcohol exposure. The [3H]biotin uptake results showed that chronic ethanol feeding in rats leads to a significant inhibition in carrier-mediated biotin transport across both renal brush border and basolateral membrane domains. This inhibition was associated with a marked reduction in the level of expression of SMVT protein, mRNA, and heterogenous nuclear RNA (hnRNA). Furthermore, studies with transgenic mice carrying the SLC5A6 5′-regulatory region showed that chronic alcohol feeding leads to a significant decrease in promoter activity. Studies with HK-2 cells chronically exposed to alcohol again showed a marked reduction in carrier-mediated biotin uptake, which was associated with a significant reduction in promoter activity of the human SLC5A6 5′-regulatory region. These findings demonstrate for the first time that chronic ethanol feeding inhibits renal biotin transport and that this effect is, at least in part, being exerted at the transcriptional level. PMID:21209005

  12. Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process.

    PubMed

    Subramanian, Veedamali S; Subramanya, Sandeep B; Said, Hamid M

    2011-03-01

    Normal body homeostasis of biotin is critically dependent on its renal recovery by kidney proximal tubular epithelial cells, a process that is mediated by the sodium-dependent multivitamin transporter (SMVT; a product of the SLC5A6 gene). Chronic ethanol consumption interferes with the renal reabsorption process of a variety of nutrients, including water-soluble vitamins. To date, however, there is nothing known about the effect of chronic alcohol feeding on physiological and molecular parameters of the renal biotin reabsorption process. We addressed these issues using rats and transgenic mice carrying the human SLC5A6 (P1P2) 5'-regulatory region as an in vivo model systems of alcohol exposure, and cultured human renal proximal tubular epithelial HK-2 cells chronically exposed to alcohol as an in vitro model of alcohol exposure. The [(3)H]biotin uptake results showed that chronic ethanol feeding in rats leads to a significant inhibition in carrier-mediated biotin transport across both renal brush border and basolateral membrane domains. This inhibition was associated with a marked reduction in the level of expression of SMVT protein, mRNA, and heterogenous nuclear RNA (hnRNA). Furthermore, studies with transgenic mice carrying the SLC5A6 5'-regulatory region showed that chronic alcohol feeding leads to a significant decrease in promoter activity. Studies with HK-2 cells chronically exposed to alcohol again showed a marked reduction in carrier-mediated biotin uptake, which was associated with a significant reduction in promoter activity of the human SLC5A6 5'-regulatory region. These findings demonstrate for the first time that chronic ethanol feeding inhibits renal biotin transport and that this effect is, at least in part, being exerted at the transcriptional level.

  13. Self limiting features of accidental criticality in a solution system

    SciTech Connect

    Malenfant, R.E.

    1988-01-01

    Experience with the SHEBA solution critical assembly during validation testing of accidental criticality alarm detectors provided several insights into the character of potential accidental excursions. Two observations were of particular interest. First, it is nearly impossible to maintain a solution system, particularly one employing low-enrichment material, in a constant state. If super-critical, the system will heat up, expand (or form bubbles), return to a sub-critical state, and shut down of its own accord without going into short period oscillations. Second, a very slow change in the system could produce a long ''pulse'' resulting in lengthy exposures, a high dose, but a low dose rate. The experiments dramatically contradicted the popular contention that accidental criticality is characterized by a blue flash, a clap of thunder, and violet expulsion of material. 5 refs., 3 figs., 4 tabs.

  14. Chronic in utero Buprenorphine Exposure Causes Prolonged Respiratory Effects in the Guinea Pig Neonate

    PubMed Central

    Wallisch, Michael; Subban, Chinmayee V.; Nettleton, Rosemary T.; Olsen, George D.

    2010-01-01

    Our laboratory studies the effects of in utero opioid exposure on the neonate. In this work we test the effects of chronic in utero exposure to buprenorphine on the neonate. Buprenorphine is a promising candidate for treatment of opioid addiction during pregnancy and it has been suggested to decrease the neonatal abstinence syndrome in human infants. In our guinea pig model, we focused not only on the respiratory effects of in utero exposure on the neonate, but also studied withdrawal signs in the neonate, a major concern of all opioid treatment during pregnancy. Pregnant guinea pigs were treated with daily subcutaneous injections of 0.1 mg/kg buprenorphine during the second half of gestation. We measured weight, locomotor activity and respiratory function in pups of ages 3 to 14 days. Respiratory response was recorded using a two-chamber plethysmograph, while pups were breathing either room air or 5% CO2. Our results show that chronic in utero exposure to buprenorphine induces respiratory effects up to day 14 after birth, while earlier studies have shown that effects of either in utero methadone or morphine only persist in the first week after birth in the guinea pig model. These data provide important information for clinical trials of buprenorphine treatment suggesting that duration and severity of respiratory effects of in utero buprenorphine exposure should be monitored. PMID:20043989

  15. Chronic nicotine and ethanol exposure both disrupt central ventilatory responses to hypoxia in bullfrog tadpoles.

    PubMed

    Taylor, Barbara E; Brundage, Cord M; McLane, Lisa H

    2013-07-01

    The central hypoxic ventilatory response (HVR) comprises a reduction in ventilatory activity that follows a peripherally mediated ventilatory augmentation. Chronic early developmental exposure to nicotine or ethanol are both known to impair the peripherally mediated HVR, and nicotine impairs the central HVR, but the effect of ethanol on the central HVR has not been investigated. Additionally, chronic nicotine and ethanol exposure are known to impair ventilatory responses to hypercapnia in bullfrog tadpoles but HVRs have not been tested. Here early and late metamorphic tadpoles were exposed to either 30 μg/L nicotine or 0.15-0.05 g/dL ethanol for 10 wk. Tadpole brainstems were then isolated and the neurocorrelates of ventilation were monitored in vitro over 180 min of hypoxia (PO2=5.05±1.04 kPa). Both nicotine and ethanol exposure disrupted central HVRs. Nicotine impairments were dependent on development. Central HVRs were impaired only in early metamorphic nicotine-exposed tadpoles. Both early and late metamorphic ethanol-exposed tadpoles failed to exhibit central HVRs. Thus, central HVRs are impaired following both nicotine and ethanol exposure. Such failure to decrease ventilatory activity during hypoxia indicates that central hypoxic ventilatory depression is an active suppression of neural activity in response to hypoxia rather than a metabolic consequence of O2 limitation, and that exposure to ethanol (across development) or nicotine (during early development) disrupts mechanisms that normally induce active ventilatory depression.

  16. Chronic in utero buprenorphine exposure causes prolonged respiratory effects in the guinea pig neonate.

    PubMed

    Wallisch, Michael; Subban, Chinmayee V; Nettleton, Rosemary T; Olsen, George D

    2010-01-01

    Our laboratory studies the effects of in utero opioid exposure on the neonate. In this work we test the effects of chronic in utero exposure to buprenorphine on the neonate. Buprenorphine is a promising candidate for treatment of opioid addiction during pregnancy and it has been suggested to decrease the neonatal abstinence syndrome in human infants. In our guinea pig model, we focused not only on the respiratory effects of in utero exposure on the neonate, but also studied withdrawal signs in the neonate, a major concern of all opioid treatment during pregnancy. Pregnant guinea pigs were treated with daily subcutaneous injections of 0.1mg/kg buprenorphine during the second half of gestation. We measured weight, locomotor activity and respiratory function in pups of ages 3 to 14 days. Respiratory response was recorded using a two-chamber plethysmograph, while pups were breathing either room air or 5% CO(2). Our results show that chronic in utero exposure to buprenorphine induces respiratory effects up to day 14 after birth, while earlier studies have shown that effects of either in utero methadone or morphine only persist in the first week after birth in the guinea pig model. These data provide important information for clinical trials of buprenorphine treatment suggesting that duration and severity of respiratory effects of in utero buprenorphine exposure should be monitored.

  17. 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.

  18. Intestinal transport of hexoses in the rat following chronic heat exposure

    NASA Technical Reports Server (NTRS)

    Carpenter, M.; Musacchia, X. J.

    1979-01-01

    The study examines intestinal transport of sugars (D-glucose and D-galactose) in vitro and assesses organ maintenance in chronically heat-exposed rats. The results suggest that the response of intestinal absorption to heat exposure in the rat involves changes in intestinal weight and in glucose utilization. Despite the reduction in total intestinal weight, the ability of intestinal tissue to transport hexose per unit weight remains stable. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function of the amount of food consumed. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity.

  19. C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.

    PubMed

    Kanteti, Rajani; Dhanasingh, Immanuel; El-Hashani, Essam; Riehm, Jacob J; Stricker, Thomas; Nagy, Stanislav; Zaborin, Alexander; Zaborina, Olga; Biron, David; Alverdy, John C; Im, Hae Kyung; Siddiqui, Shahid; Padilla, Pamela A; Salgia, Ravi

    2016-01-01

    We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.

  20. 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

  1. History of accidental hypothermia☆

    PubMed Central

    Guly, Henry

    2011-01-01

    Death from exposure to cold has been recognised for thousands of years but hypothermia as a clinical condition was not generally recognised until the mid-20th century and then only in extreme conditions such as immersion in cold water or snow. In the UK, hypothermia in less extreme conditions was not generally recognised until the 1960s. Recognition of hypothermia required the temperature to be measured and this did not become a clinical tool until the late 1800s and it was not used routinely until the early 1900s. Although John Hunter and James Curry did some physiological experiments in the 1700s, detailed physiological experiments were not done until the early 20th century and the use of therapeutic hypothermia for malignancy and in anaesthesia in the 1930s and 1940s provided more impetus for investigating the physiology of hypothermia in humans and familiarising the medical profession with measuring core temperatures. PMID:21036455

  2. Association between subchronic and chronic lead exposure and levels of antioxidants and chemokines.

    PubMed

    Dobrakowski, Michał; Kasperczyk, Aleksandra; Pawlas, Natalia; Birkner, Ewa; Hudziec, Edyta; Chwalińska, Ewa; Kasperczyk, Sławomir

    2016-10-01

    This study aimed to compare the influence of lead on the non-enzymatic antioxidant defenses and the levels of chemokines in workers subchronically and chronically exposed to lead. The study population was divided into three groups. The first group consisted of male workers subchronically exposed to lead for 40 ± 3.2 days, while the second group included male workers chronically exposed to lead. The third group was a control group. The levels of uric acid and bilirubin were significantly higher after a subchronic exposure to lead compared to the baseline by 22 and 35 %, respectively. Similarly, the values of total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) increased by 15, 50, and 33 %, respectively. At the same time, the levels of thiol groups and albumin decreased by 5 and 8 %, respectively. Additionally, the levels of interleukin-8 (IL-8) and macrophage inflammatory protein-1β (MIP-1β) were significantly higher after a subchronic exposure to lead compared to the baseline by 34 and 20 %, respectively. Moreover, IL-8 level was significantly higher by 40 % in the group of workers chronically exposed to lead than in the control group, while the level of interferon gamma-induced protein-10 (IP-10) was significantly lower by 28 %. Similar to chronic lead exposure, subchronic exposure to lead is associated with elevated blood levels of uric acid and bilirubin in humans. This probably results in increased TAC value despite thiol depletion. However, the compensatory activation of non-enzymatic antioxidant defenses seems to be insufficient to protect against lead-induced oxidative stress, which may be additively enhanced by the pro-inflammatory action of chemokines, especially IL-8.

  3. 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.

  4. Neuropathy associated with chronic low level exposure to n-hexane

    SciTech Connect

    Ruff, R.L.; Petito, C.K.; Acheson, L.S.

    1981-05-01

    Concentrations of n-hexane greater than the threshold limit value (TLV) of 500 ppm are known to produce peripheral neuropathy. This report describes the case of a worker who developed peripheral neuropathy, with a histologic pattern characteristic of n-hexane toxicity, after chronic on-the-job exposure to n-hexane at concentrations less than 450 ppm. We suggest that the current TLV for n-hexane be reevaluated.

  5. Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium

    DTIC Science & Technology

    2009-09-01

    an anti- oxidant agent and/or an NMDA receptor antagonist will reduce neurotoxicity resulting from chronic exposure to DU. This hypothesis is based...DU-induced oxidative stress. As prescribed by the Statement of Work, efforts continued in year 2 on Tasks 1 (drug therapies to reverse DU-induced...SUBJECT TERMS depleted uranium, glutamate release, military disease, hippocampus, oxidative stress, neuroprotectant drugs 16. SECURITY

  6. 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

  7. 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

  8. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures.

    PubMed

    Wang, Ning; Dorman, Rebecca A; Ingersoll, Christopher G; Hardesty, Doug 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 1 mg K/L to 3 mg 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.

  9. Neuropathy associated with chronic low level exposure to n-hexane.

    PubMed

    Ruff, R L; Petito, C K; Acheson, L S

    1981-05-01

    Concentrations of n-hexane greater than the threshold limit value (TLV) of 500 ppm are known to produce peripheral neuropathy. This report describes the case of a worker who developed peripheral neuropathy, with a histologic pattern characteristic of n-hexane toxicity, after chronic on-the-job exposure to n-hexane at concentrations less than 450 ppm. We suggest that the current TLV for n-hexane be reevaluated.

  10. [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.

  11. Welding-related brain and functional changes in welders with chronic and low-level exposure.

    PubMed

    Lee, Eun-Young; Flynn, Michael R; Lewis, Mechelle M; Mailman, Richard B; Huang, Xuemei

    2017-06-23

    Although an essential nutrient, manganese (Mn) can be toxic at high doses. There is, however, uncertainty regarding the effects of chronic low-level Mn-exposure. This review provides an overview of Mn-related brain and functional changes based on studies of a cohort of asymptomatic welders who had lower Mn-exposure than in most previous work. In welders with low-level Mn-exposure, we found: 1) Mn may accumulate in the brain in a non-linear fashion: MRI R1 (1/T1) signals significantly increased only after a critical level of exposure was reached (e.g., ≥300 welding hours in the past 90days prior to MRI). Moreover, R1 may be a more sensitive marker to capture short-term dynamic changes in Mn accumulation than the pallidal index [T1-weighted intensity ratio of the globus pallidus vs. frontal white matter], a traditional marker for Mn accumulation; 2) Chronic Mn-exposure may lead to microstructural changes as indicated by lower diffusion tensor fractional anisotropy values in the basal ganglia (BG), especially when welding years exceeded more than 30 years; 3) Mn-related subtle motor dysfunctions can be captured sensitively by synergy metrics (indices for movement stability), whereas traditional fine motor tasks failed to detect any significant differences; and 4) Iron (Fe) also may play a role in welding-related neurotoxicity, especially at low-level Mn-exposure, evidenced by higher R2* values (an estimate for brain Fe accumulation) in the BG. Moreover, higher R2* values were associated with lower phonemic fluency performance. These findings may guide future studies and the development of occupation- and public health-related polices involving Mn-exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Chronic Water-Pipe Smoke Exposure Induces Injurious Effects to Reproductive System in Male Mice

    PubMed Central

    Ali, Badreldin H.; Al Balushi, Khalid A.; Ashique, Mohammed; Shalaby, Asem; Al Kindi, Mohammed A.; Adham, Sirin A.; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Nemmar, Abderrahim

    2017-01-01

    There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine–protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone (LH) concentrations were also measured. Chronic WPS exposure induced a significant decrease of testosterone and estradiol, and a slight but significant increase of LH. Glutathione reductase, catalase, and ascorbic acid were significantly decreased following WPS exposure. Plasma concentration of leptin was significantly decreased by WPS exposure, whereas that of tumor necrosis factor α and interleukin 6 was significantly increased. Histopathological analysis of the testes revealed the presence of a marked reduction in the diameter of the seminiferous tubules with reduced spermatogenesis. Transmission electron microscopy examination showed irregular thickening and wrinkling of the basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1 was overexpressed in the testis of the mice exposed to WPS and was not detected in the control. The urine concentration of cotinine, the predominant metabolite of nicotine, was significantly increased in the WPS-exposed group compared with the control group. We conclude that chronic exposure to WPS induces damaging effects to the reproductive system in male mice. If this can be confirmed in humans, it would be an additional concern to an already serious public health problem, especially with the increased use of

  13. Chronic Water-Pipe Smoke Exposure Induces Injurious Effects to Reproductive System in Male Mice.

    PubMed

    Ali, Badreldin H; Al Balushi, Khalid A; Ashique, Mohammed; Shalaby, Asem; Al Kindi, Mohammed A; Adham, Sirin A; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Nemmar, Abderrahim

    2017-01-01

    There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine-protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone (LH) concentrations were also measured. Chronic WPS exposure induced a significant decrease of testosterone and estradiol, and a slight but significant increase of LH. Glutathione reductase, catalase, and ascorbic acid were significantly decreased following WPS exposure. Plasma concentration of leptin was significantly decreased by WPS exposure, whereas that of tumor necrosis factor α and interleukin 6 was significantly increased. Histopathological analysis of the testes revealed the presence of a marked reduction in the diameter of the seminiferous tubules with reduced spermatogenesis. Transmission electron microscopy examination showed irregular thickening and wrinkling of the basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1 was overexpressed in the testis of the mice exposed to WPS and was not detected in the control. The urine concentration of cotinine, the predominant metabolite of nicotine, was significantly increased in the WPS-exposed group compared with the control group. We conclude that chronic exposure to WPS induces damaging effects to the reproductive system in male mice. If this can be confirmed in humans, it would be an additional concern to an already serious public health problem, especially with the increased use of WPS

  14. Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury

    PubMed Central

    Nicoll, Amanda; Moore, David; Njoku, Dolores; Hockey, Brad

    2012-01-01

    Volatile anaesthetic agents are known to cause acute hepatitis and fulminant hepatic failure in susceptible individuals. Four patients were identified with prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method (RUCAM) drug causality scale was used to determine the likelihood of volatile anaesthetics causing the chronic liver injury. We describe four cases of volatile anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth followed a more typical pattern of acute hepatitis; however, resolution took a few months. These cases all occurred with modern volatile anaesthetics, predominantly sevoflurane, and all cases were proven with specific antibody tests, liver histology and a drug causality scale. This is the first report of chronic liver injury due to volatile anaesthetic exposure. PMID:23131606

  15. Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury.

    PubMed

    Nicoll, Amanda; Moore, David; Njoku, Dolores; Hockey, Brad

    2012-11-06

    Volatile anaesthetic agents are known to cause acute hepatitis and fulminant hepatic failure in susceptible individuals. Four patients were identified with prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method (RUCAM) drug causality scale was used to determine the likelihood of volatile anaesthetics causing the chronic liver injury. We describe four cases of volatile anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth followed a more typical pattern of acute hepatitis; however, resolution took a few months. These cases all occurred with modern volatile anaesthetics, predominantly sevoflurane, and all cases were proven with specific antibody tests, liver histology and a drug causality scale. This is the first report of chronic liver injury due to volatile anaesthetic exposure.

  16. Chronic nicotine exposure augments gustatory plasticity in Caenorhabditis elegans: involvement of dopamine signaling.

    PubMed

    Matsuura, Tetsuya; Urushihata, Takuya

    2015-01-01

    The chemotaxis of wild-type NaCl-conditioned nematodes exposed to 100 mM NaCl, maintained on a growth medium containing 0.3 mM nicotine from first larva to young adult (YA) hermaphrodite, was significantly weaker than the chemotaxis of those maintained on a medium without nicotine. The result indicates that chronic nicotine exposure augments gustatory plasticity. The gustatory plasticity was also augmented when tph-1 mutants, with a defect in serotonin biosynthesis, were maintained on a medium containing nicotine until the YA stage. Chronic nicotine exposure did not augment gustatory plasticity in bas-1 mutants, which had defects in both serotonin and dopamine biosynthesis, and in cat-2 mutants, which had a defect in dopamine biosynthesis. However, augmentation of gustatory plasticity was observed when bas-1 and cat-2 mutants were maintained on a growth medium containing nicotine along with dopamine, suggesting that dopamine signaling is involved in the augmentation of gustatory plasticity due to chronic nicotine exposure.

  17. Induction of maternal behavior in adult female rats following chronic morphine exposure during puberty.

    PubMed

    Byrnes, Elizabeth M; Rigero, Beth A; Bridges, Robert S

    2003-12-01

    The peripubertal period in the female rat is the time when the stimulatory effects of opioids on prolactin (PRL) secretion develop. In the adult rat, the administration of chronic high-dose morphine has been shown to attenuate the ability of opiates to stimulate PRL secretion. One function of PRL in adult virgin rats is the induction of maternal behavior. The present study examined whether chronic high-dose morphine exposure during the peripubertal period alters PRL-mediated induction of maternal behavior in adult female rats. Two groups of juvenile female rats were administered increasing doses of morphine or vehicle (s.c.) from age 30 to 50 days. As adults, these females either remained intact, or were ovariectomized and treated with a PRL-dependent, steroid hormone regimen that stimulates a rapid onset of maternal behavior. All females were then exposed daily to rat foster pups to determine whether peripubertal morphine exposure affected their latencies to induce maternal behavior. Morphine treatment resulted in a delay in vaginal opening and a temporary reduction in the rate of weight gain; however, the rate of onset of maternal behavior was unaffected by peripubertal morphine treatment. Thus, chronic morphine exposure in the pubertal female did not impact the expression of pup-induced maternal care.

  18. Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure.

    PubMed

    Gimenez-Rivera, Vladimir-Andrey; Siebenhaar, Frank; Zimmermann, Carolin; Siiskonen, Hanna; Metz, Martin; Maurer, Marcus

    2016-12-01

    Allergic contact dermatitis is a chronic T cell-driven inflammatory skin disease that is caused by repeated exposure to contact allergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its pathogenesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murine models for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type and MC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergic contact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficient Kit(W-sh/W-sh) (Sash) and MCPT5-Cre(+)iDTR(+) mice compared with wild-type mice. Local engraftment with MCs protected Sash mice from exacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevated levels of IFN-γ, IL-17α, and IL-23, as well as increased accumulation of Ag-specific IFN-γ-producing CD8(+) tissue-resident memory T (TRM) cells. The CD8(+) T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous TRM cells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skin inflammation induced by repeated allergen challenge, at least in part, via effects on CD8(+) TRM cells. MCs may notably influence the course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms may lead to better approaches for the treatment of this common, disabling, and costly condition.

  19. Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure.

    PubMed

    Claussen, Catherine M; Dafny, Nachum

    2015-09-01

    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 10.0mg/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 was 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 were observed for the 2.5 and 10.0mg/kg MPD exposed groups. For 2.5mg/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 10.0mg/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 10.0mg/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

  20. 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

  1. Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol feeding/exposure

    PubMed Central

    Subramanya, Sandeep B.; Subramanian, Veedamali S.; Sekar, V. Thillai

    2011-01-01

    Thiamin is important for normal function of pancreatic acinar cells, but little is known about its mechanism of uptake and about the effect of chronic alcohol use on the process. We addressed these issues using freshly isolated rat primary and rat-derived cultured AR42J pancreatic acinar cells as models. Results showed thiamin uptake by both primary and cultured AR42J pancreatic acinar cells to be via a specific carrier-mediated mechanism and that both of the thiamin transporters 1 and 2 (THTR-1 and THTR-2) are expressed in these cells. Chronic alcohol feeding of rats was found to lead to a significant inhibition of carrier-mediated thiamin uptake by pancreatic acinar cells and was associated with a significant reduction in level of expression of THTR-1 and THTR-2 at the protein and mRNA levels. Chronic exposure (96 h) of AR42J cells to alcohol also led to a significant decreased carrier-mediated thiamin uptake, an effect that was associated with a significant decrease in the activity of the human SLC19A2 and SLC19A3 promoters expressed in these cells. We also examined the effect of chronic alcohol feeding of rats on level of expression of key thiamin metabolizing enzymes (thiamin phosphokinase and thiamin pyrophosphatase) as well as on level of expression of the mitochondrial thiamin pyrophosphate transporter of pancreatic acinar cells and observed a significant inhibition in all these parameters. These results demonstrate for the first time that thiamin uptake by pancreatic acinar cells is via a carrier-mediated process and that both the THTR-1 as well as THTR-2 are expressed in these cells. Also, chronic alcohol feeding/exposure inhibits thiamin uptake process and the inhibition is, at least in part, being exerted at the transcriptional level. Furthermore, chronic alcohol feeding also negatively impacts intracellular parameters of thiamin metabolism in pancreatic acinar cells. PMID:21868632

  2. Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol feeding/exposure.

    PubMed

    Subramanya, Sandeep B; Subramanian, Veedamali S; Sekar, V Thillai; Said, Hamid M

    2011-11-01

    Thiamin is important for normal function of pancreatic acinar cells, but little is known about its mechanism of uptake and about the effect of chronic alcohol use on the process. We addressed these issues using freshly isolated rat primary and rat-derived cultured AR42J pancreatic acinar cells as models. Results showed thiamin uptake by both primary and cultured AR42J pancreatic acinar cells to be via a specific carrier-mediated mechanism and that both of the thiamin transporters 1 and 2 (THTR-1 and THTR-2) are expressed in these cells. Chronic alcohol feeding of rats was found to lead to a significant inhibition of carrier-mediated thiamin uptake by pancreatic acinar cells and was associated with a significant reduction in level of expression of THTR-1 and THTR-2 at the protein and mRNA levels. Chronic exposure (96 h) of AR42J cells to alcohol also led to a significant decreased carrier-mediated thiamin uptake, an effect that was associated with a significant decrease in the activity of the human SLC19A2 and SLC19A3 promoters expressed in these cells. We also examined the effect of chronic alcohol feeding of rats on level of expression of key thiamin metabolizing enzymes (thiamin phosphokinase and thiamin pyrophosphatase) as well as on level of expression of the mitochondrial thiamin pyrophosphate transporter of pancreatic acinar cells and observed a significant inhibition in all these parameters. These results demonstrate for the first time that thiamin uptake by pancreatic acinar cells is via a carrier-mediated process and that both the THTR-1 as well as THTR-2 are expressed in these cells. Also, chronic alcohol feeding/exposure inhibits thiamin uptake process and the inhibition is, at least in part, being exerted at the transcriptional level. Furthermore, chronic alcohol feeding also negatively impacts intracellular parameters of thiamin metabolism in pancreatic acinar cells.

  3. Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss.

    PubMed

    Rodrigues, S; Antunes, S C; Correia, A T; Nunes, B

    2016-03-01

    Erythromycin (ERY) is a macrolide antibiotic used in human and veterinary medicine, and has been detected in various aquatic compartments. Recent studies have indicated that this compound can exert biological activity on non-target organisms environmentally exposed. The present study aimed to assess the toxic effects of ERY in Oncorhynchus mykiss after acute and chronic exposures. The here adopted strategy involved exposure to three levels of ERY, the first being similar to concentrations reported to occur in the wild, thus ecologically relevant. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers in gills and liver. Genotoxic endpoints, reflecting different types of genetic damage in blood cells, were also determined, by performing analysis of genetic damage (determination of the genetic damage index, GDI, measured by comet assay) and of erythrocytic nuclear abnormalities (ENAs). The results suggest the occurrence of a mild, but significant, oxidative stress scenario in gills. For acutely exposed organisms, significant alterations were observed in CAT and GRed activities, and also in TBARS levels, which however are modifications with uncertain biological interpretation, despite indicating involvement of an oxidative effect and response. After chronic exposure, a significant decrease of CAT activity, increase of GPx activity and TBARS levels in gills was noticed. In liver, significant decrease in TBARS levels were observed in both exposures. Comet and ENAs assays indicated significant increases on genotoxic damage of O. mykiss, after erythromycin exposures. This set of data (acute and chronic) suggests that erythromycin has the potential to induce DNA strand breaks in blood cells, and demonstrate the induction of chromosome breakage and/or segregational abnormalities. Overall results indicate that both DNA damaging effects induced by

  4. 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

  5. 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.

  6. History of accidental hypothermia.

    PubMed

    Guly, Henry

    2011-01-01

    Death from exposure to cold has been recognised for thousands of years but hypothermia as a clinical condition was not generally recognised until the mid-20th century and then only in extreme conditions such as immersion in cold water or snow. In the UK, hypothermia in less extreme conditions was not generally recognised until the 1960s. Recognition of hypothermia required the temperature to be measured and this did not become a clinical tool until the late 1800s and it was not used routinely until the early 1900s. Although John Hunter and James Curry did some physiological experiments in the 1700s, detailed physiological experiments were not done until the early 20th century and the use of therapeutic hypothermia for malignancy and in anaesthesia in the 1930s and 1940s provided more impetus for investigating the physiology of hypothermia in humans and familiarising the medical profession with measuring core temperatures. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Lactobacillus rhamnosus GG Effect on Behavior of Zebrafish During Chronic Ethanol Exposure.

    PubMed

    Schneider, Ana Claudia Reis; Rico, Eduardo Pacheco; de Oliveira, Diogo Losch; Rosemberg, Denis Broock; Guizzo, Ranieli; Meurer, Fábio; da Silveira, Themis Reverbel

    2016-01-01

    Ethanol is a widely consumed drug, which acts on the central nervous system to induce behavioral alterations ranging from disinhibition to sedation. Recent studies have produced accumulating evidence for the therapeutic role of probiotic bacteria in behavior. We aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) on the behavior of adult zebrafish chronically exposed to ethanol. Adult wild-type zebrafish were randomly divided into four groups, each containing 15 fish. The following groups were formed: Control (C), received unsupplemented feed during the trial period; Probiotic (P), fed with feed supplemented with LGG; Ethanol (E), received unsupplemented feed and 0.5% of ethanol directly added to the tank water; and Probiotic+Ethanol (P+E), group under ethanol exposure (0.5%) and fed with LGG supplemented feed. After 2 weeks of exposure, the novel tank test was used to evaluate fish behavior, which was analyzed using computer-aided video tracking. LGG alone did not alter swimming behavior of the fish. Ethanol exposure led to robust behavioral effects in the form of reduced anxiety levels, as indicated by increased vertical exploration and more time spent in the upper region of the novel tank. The group exposed to ethanol and treated with LGG behaved similarly to animals exposed to ethanol alone. Taken together, these results show that zebrafish behavior was not altered by LGG per se, as seen in murine models. This was the first study to investigate the effects of a probiotic diet on behavior after a chronic ethanol exposure.

  8. Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris)

    PubMed Central

    Moffat, Christopher; Pacheco, Joao Goncalves; Sharp, Sheila; Samson, Andrew J.; Bollan, Karen A.; Huang, Jeffrey; Buckland, Stephen T.; Connolly, Christopher N.

    2015-01-01

    The global decline in the abundance and diversity of insect pollinators could result from habitat loss, disease, and pesticide exposure. The contribution of the neonicotinoid insecticides (e.g., clothianidin and imidacloprid) to this decline is controversial, and key to understanding their risk is whether the astonishingly low levels found in the nectar and pollen of plants is sufficient to deliver neuroactive levels to their site of action: the bee brain. Here we show that bumblebees (Bombus terrestris audax) fed field levels [10 nM, 2.1 ppb (w/w)] of neonicotinoid accumulate between 4 and 10 nM in their brains within 3 days. Acute (minutes) exposure of cultured neurons to 10 nM clothianidin, but not imidacloprid, causes a nicotinic acetylcholine receptor-dependent rapid mitochondrial depolarization. However, a chronic (2 days) exposure to 1 nM imidacloprid leads to a receptor-dependent increased sensitivity to a normally innocuous level of acetylcholine, which now also causes rapid mitochondrial depolarization in neurons. Finally, colonies exposed to this level of imidacloprid show deficits in colony growth and nest condition compared with untreated colonies. These findings provide a mechanistic explanation for the poor navigation and foraging observed in neonicotinoid treated bumblebee colonies.—Moffat, C., Pacheco, J. G., Sharp, S., Samson, A. J., Bollan, K. A., Huang, J., Buckland, S. T., Connolly, C. N. Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris). PMID:25634958

  9. Chronic cocaine exposure induces putamen glutamate and glutamine metabolite abnormalities in squirrel monkeys

    PubMed Central

    Liu, Xiaoxu; Jensen, J. Eric; Gillis, Timothy E.; Zuo, Chun S.; Prescot, Andrew P.; Brimson, Melanie; Cayetano, Kenroy; Renshaw, Perry F.

    2011-01-01

    Rationale Chronic cocaine exposure has been associated with progressive brain structural and functional changes. Clarifying mechanisms underlying cocaine’s progressive brain effects may help in the development of effective cocaine abuse treatments. Objectives We used a controlled squirrel monkey model of chronic cocaine exposure (45 mg/kg/week for 9 months) combined with ultra-high magnetic field (9.4 T) proton magnetic resonance spectroscopy to prospectively measure putamen metabolite changes. Methods Proton metabolites were measured with a STEAM sequence, quantified with LCModel using a simulated basis set, and expressed as metabolite/total creatine (tCr) ratios. Results We found cocaine-induced time-dependent changes in putamen glutamate/tCr and glutamine/tCr metabolite ratios suggestive of altered glutamate compartmentalization, neurotransmission, and metabolism. By contrast, saline-treated monkeys exhibited no metabolite changes over time. The time course of cocaine-induced metabolite abnormalities we detected is consistent with the apparent time course of glutamate abnormalities identified in a cross-sectional study in human cocaine users, as well as with microdialysis findings in rodent models of repeated cocaine exposure. Conclusions Together, these findings suggests that this squirrel monkey model may be useful for characterizing glutamatergic changes associated with cocaine exposure and for determining efficacies of treatments designed to mitigate cocaine-induced glutamatergic system dysfunction. PMID:21494788

  10. Effect of low-level NO/sub 2/ chronic exposure on elastase-induced emphysema

    SciTech Connect

    Lafuma, C.; Harf, A.; Lange, F.; Bozzi, L.; Poncy, J.L.; Bignon, J.

    1987-06-01

    The effect of chronic exposure to 2 ppm nitrogen dioxide (NO/sub 2/) for 8 hr a day, 5 days a week, for 8 weeks was assessed in normal and emphysematous hamsters by measuring (1) lung morphometry (mean linear intercept (Lm) and internal surface area (ISA)), (2) lung mechanics (lung volume, compliance and coefficient of static deflation, pressure-volume curve fitted to an exponential equation), and (3) serum elastolytic activity and protease inhibitor capacity. Emphysema was induced by a single intratracheal injection of 6 IU porcine pancreatic elastase. Four groups of animals were used: control, NO/sub 2/-exposed, elastase-treated, and NO/sub 2/-exposed postelastase. Results show that NO/sub 2/ exposure alone induced mild emphysematous lesions whose degree of severity was of the same order as that of the lesions induced by 6 IU elastase. Exposure to 2 ppm NO/sub 2/ enhanced elastase-induced emphysema. By contrast, study of lung mechanics revealed no difference between the control and NO/sub 2/-exposed groups or between the elastase-treated animals exposed to NO/sub 2/ and those not so exposed. Lastly, results suggest that chronic exposure to 2 ppm NO/sub 2/ may cause individuals with inherited or acquired emphysematous lesions to develop more severe emphysema.

  11. Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

    PubMed

    Osterndorff-Kahanek, Elizabeth A; Becker, Howard C; Lopez, Marcelo F; Farris, Sean P; Tiwari, Gayatri R; Nunez, Yury O; Harris, R Adron; Mayfield, R Dayne

    2015-01-01

    Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each region, there was little gene overlap across time (~20%). All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

  12. Chronic Exposure to Cadmium Disrupts the Adrenal Gland Activity of the Newt Triturus carnifex (Amphibia, Urodela)

    PubMed Central

    Gay, Flaminia; Laforgia, Vincenza; Caputo, Ivana; Esposito, Carla; Lepretti, Marilena

    2013-01-01

    We intended to verify the safety of the freshwater values established for cadmium by the European Community and the Italian Ministry of Health in drinking water (5 μg/L) and sewage waters (20 μg/L). Therefore, we chronically exposed the newt Triturus carnifex to 5 μg/L and 20 μg/L doses of cadmium, respectively, during 3 and 9 months and verified the effects on the adrenal gland. We evaluated the serum concentrations of adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, norepinephrine, and epinephrine. During the 3-month exposure, both doses of cadmium decreased ACTH and corticosterone serum levels and increased aldosterone and epinephrine serum levels. During the 9-month exposure, the 5 μg/L dose decreased ACTH and increased aldosterone and epinephrine serum levels; the 20 μg/L dose decreased norepinephrine and epinephrine serum levels, without affecting the other hormones. It was concluded that (1) chronic exposure to the safety values established for cadmium disrupted the adrenal gland activity and (2) the effects of cadmium were related both to the length of exposure and the dose administered. Moreover, our results suggest probable risks to human health, due to the use of water contaminated by cadmium. PMID:23971036

  13. Chronic Chlorpyrifos Exposure Does Not Promote Prostate Cancer in Prostate Specific PTEN Mutant Mice

    PubMed Central

    Svensson, Robert U.; Bannick, Nadine L.; Marin, Maximo J.; Robertson, Larry W.; Lynch, Charles F.; Henry, Michael D.

    2014-01-01

    Environmental factors are likely to interact with genetic determinants to influence prostate cancer progression. The Agricultural Health Study has identified an association between exposure to organophosphorous pesticides including chlorpyrifos, and increased prostate cancer risk in pesticide applicators with a first-degree family history of this disease. Exploration of this potential gene-environment interaction would benefit from the development of a suitable animal model. Utilizing a previously described mouse model that is genetically predisposed to prostate cancer through a prostate-specific heterozygous PTEN deletion, termed C57/Luc/Ptenp+/−, we used bioluminescence imaging and histopathological analyses to test whether chronic exposure to chlorpyrifos in a grain-based diet for 32 weeks was able to promote prostate cancer development. Chronic exposure to chlorpyrifos in the diet did not promote prostate cancer development in C57/Luc/Ptenp+/− mice despite achieving sufficient levels to inhibit acetylcholinesterase activity in plasma. We found no significant differences in numbers of murine prostatic intraepithelial neoplasia lesions or disease progression in chlorpyrifos versus control treated animals up to 32 weeks. The mechanistic basis of pesticide-induced prostate cancer may be complex and may involve other genetic variants, multiple genes, or nongenetic factors that might alter prostate cancer risk during pesticide exposure in agricultural workers. PMID:23758150

  14. Occupational Exposures and Chronic Kidney Disease: Possible associations with endotoxin and ultrafine particles

    PubMed Central

    Sponholtz, Todd R.; Sandler, Dale P.; Parks, Christine G.; Applebaum, Katie M.

    2015-01-01

    Background Chronic kidney disease (CKD) carries a high public health burden yet there is limited research on occupational factors, which are examined in this retrospective case-control study. Methods Newly diagnosed cases of CKD (n=547) and controls (n=508) from North Carolina provided detailed work histories in telephone interviews. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results There was heterogeneity in the association of CKD and agricultural work, with crop production associated with increased risk and work with livestock associated with decreased risk. Work with cutting/cooling/lubricating oils was associated with a reduced risk. CKD risk was increased for working in dusty conditions. Conclusions CKD risk was reduced in subjects with occupational exposures previously reported to involve endotoxin exposure. Further, exposure to dusty conditions was consistently associated with increased risk of glomerulonephritis across industry, suggesting that research on CKD and ultrafine particulates is needed. PMID:26572099

  15. Occupational exposures and chronic kidney disease: Possible associations with endotoxin and ultrafine particles.

    PubMed

    Sponholtz, Todd R; Sandler, Dale P; Parks, Christine G; Applebaum, Katie M

    2016-01-01

    Chronic kidney disease (CKD) carries a high public health burden yet there is limited research on occupational factors, which are examined in this retrospective case-control study. Newly diagnosed cases of CKD (n = 547) and controls (n = 508) from North Carolina provided detailed work histories in telephone interviews. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). There was heterogeneity in the association of CKD and agricultural work, with crop production associated with increased risk and work with livestock associated with decreased risk. Work with cutting/cooling/lubricating oils was associated with a reduced risk. CKD risk was increased for working in dusty conditions. CKD risk was reduced in subjects with occupational exposures previously reported to involve endotoxin exposure. Further, exposure to dusty conditions was consistently associated with increased risk of glomerulonephritis across industry, suggesting that research on CKD and ultrafine particulates is needed. © 2015 Wiley Periodicals, Inc.

  16. Proteolytic activity is altered in brain tissue of rats upon chronic exposure to ozone

    SciTech Connect

    Benuck, M.; Banay-Schwartz, M.; Lajtha, A. )

    1993-01-01

    Tissue from pons medulla of rats exposed in vivo to various levels of ozone was assayed for calpain and cathepsin D activity. Chronic exposure to ozone increased calpain activity, which was 35% to 46% higher in the homogenates of animals exposed to 1.0 ppm ozone than in those of animals exposed to 0.5 ppm ozone or of controls. An increase in activity of 26% was also observed in the soluble supernatant. The increase in activity did not seem to be caused by ozone effects on calpastatin. Addition of 32 mM carnitine to the incubation mixture increased total activity 3-4 fold, making the differences in activity proportionately smaller. Cathepsin D activity was little altered. Changes in calpain activity and in the generation of free oxygen radicals have been implicated in the aging process, long-term exposure to ozone may magnify changes. Ozone exposure may cause changes in brain protein metabolism. 15 refs., 2 tabs.

  17. High-fat diet aggravates glucose homeostasis disorder caused by chronic exposure to bisphenol A.

    PubMed

    Ding, Shibin; Fan, Ying; Zhao, Nana; Yang, Huiqin; Ye, Xiaolei; He, Dongliang; Jin, Xin; Liu, Jian; Tian, Chong; Li, Hongyu; Xu, Shunqing; Ying, Chenjiang

    2014-04-01

    Epidemiological findings on the association between bisphenol A (BPA, 2,2-bis-(4-hydroxyphenyl)propane) exposure and type 2 diabetes mellitus (T2DM) are paradoxical. In animal studies, BPA has been shown to disrupt pancreatic function and blood glucose homeostasis even at a reference 'safe' level during perinatal period. In this study, we explored the effects of long-term paternal exposure to a 'safe' level of BPA on parents themselves and their offspring. Adult male genitor rats fed with either standard chow diet (STD) or high-fat diet (HFD) were treated respectively with either vehicle or BPA (50 μg/kg per day) for 35 weeks. The male rats treated with vehicle or BPA for 21 weeks were then used as sires, and the adult female rats were fed with STD during the gestation and lactation. Offspring rats were weaned on postnatal day 21 and fed with STD in later life. Metabolic parameters were recorded on the adult male rats and their adult offspring. BPA exposure disrupted glucose homeostasis and pancreatic function, and HFD aggravated these adverse effects. However, BPA exposure did not alter body weight, body fat percentage, or serum lipid. In addition, the paternal BPA exposure did not cause adverse reproductive consequence or metabolic disorder in the adult offspring. Our findings indicate that chronic exposure to a predicted 'safe' dose of BPA contributes to glucose metabolic disorders, and that HFD aggravates these adverse effects in paternal rats.

  18. Acute and chronic exposure to Tyrophagus putrescentiae induces allergic pulmonary response in a murine model

    PubMed Central

    Nuñez, Nailê Karine; dos Santos Dutra, Moisés; Barbosa, Gustavo Leivas; Morassutti, Alessandra Loureiro; de Souza, Rodrigo Godinho; Vargas, Mauro Henrique Moraes; Antunes, Géssica Luana; Silveira, Josiane Silva; da Silva, Guilherme Liberato; Pitrez, Paulo Márcio

    2016-01-01

    Background Tyrophagus putrescentiae (Tp) is a source of aeroallergen that causes allergic diseases. Objective To describe an acute and chronic murine model of allergic asthma with Tp extract with no systemic sensitization and no use of adjuvant. Methods Mites from dust sample were cultured and a raw extract was produced. Female BALB/c mice (6-8 weeks) were challenged intranasally with Tp extract or Dulbecco's phosphate-buffered saline, for 10 consecutive days (acute protocol) or for 6 weeks (chronic protocol). Twenty-four hours after the last intranasal challenge, bronchoalveolar lavage fluid (BALF) was performed for total and differential cells count, cytokine analysis, and eosinophil peroxidase activity. Lung tissue was also removed for histopathologic analysis. Results Tp extract has shown a significant increase in total cells count from BALF as well as an increase in absolute eosinophils count, eosinophil peroxidase activity, interleukin (IL)-5 and IL-13 levels, in both acute and chronic protocols. Peribronchovascular infiltrate, goblet cells hyperplasia and collagen deposition were shown in the airways of acute and chronic Tp-exposed mice. Conclusion Our data suggest that the intranasal exposure to Tp extract, with no systemic sensitization and no use of adjuvants, induces a robust allergic inflammation in the lungs of mice, in both acute and chronic models. Our Tp extract seems to be a potent allergen extract which may be used in asthma model studies. PMID:26844220

  19. Kinetics of deposition and clearance of inhaled mineral dusts during chronic exposure.

    PubMed Central

    Vincent, J H; Johnston, A M; Jones, A D; Bolton, R E; Addison, J

    1985-01-01

    New inhalation studies have been carried out with rats exposed to UICC (Union International Contre le Cancer) amosite asbestos, with the main aim of further elucidating the factors the influence the accumulation of dust in the lung during prolonged chronic exposure. The results show that, for exposure times beyond a few weeks, the lung burden rises linearly and does not level off as predicted by simple models based on ideas taken from the 1966 report of the Task Group on Lung Dynamics. Furthermore, the lung burden is found to scale directly in proportion to the exposure concentration in a way that seems to contradict the overload hypothesis stated earlier. Nevertheless, the general pattern exhibited by our results for asbestos is markedly similar to that found elsewhere for rats inhaling diesel fume, leading to the suggestion that it is general (and not specific to fibrous dust); and the hypothesis that, whereas overload of clearance can take place at high lung burdens after exposure has ceased, it is cancelled by the sustained stimulus to clearance mechanisms provided by the continuous challenge of chronic exposure. The linearity of the increase in lung burden is explained in terms of a kinetic model involving sequestration of some inhaled material to parts of the lung where it is difficult to clear. The particular sequestration model favoured is one where, the longer a particle remains in the lung without being cleared, the more likely it will be sequestrated (and therefore less likely cleared). It is believed that such ideas may eventually be useful in forming exposure-dose relations for epidemiology. PMID:2864076

  20. Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

    PubMed Central

    Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

    2009-01-01

    Malignant transformation was demonstrated in UROtsa cells following 52 wk exposure to 50 nM monomethylarsonous acid (MMAIII); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMAIII [URO-MSC(+)] and after subsequent removal of MMAIII [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMAIII, URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12 wk exposure; in particular, a significant increase in DNA single strand breaks at 12 wk exposure consistently elevated through 52 wk. The persistence of DNA damage in URO-MSC cells was assessed after a 2 wk removal of MMAIII. URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36 wk MMAIII exposure, suggesting the presence of MMAIII is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMAIII results in: the induction of DNA damage that remains elevated upon removal of MMAIII; increased levels of ROS that play a role in MMAIII induced-DNA damage; and decreased PARP activity in the presence of MMAIII. PMID:19699219

  1. Exposure to High Risk Medications is Associated with Worse Outcomes in Older Veterans with Chronic Pain

    PubMed Central

    Makris, Una E; Pugh, Mary Jo; Alvarez, Carlos A; Berlowitz, Dan R; Turner, Barbara J; Aung, KoKo; Mortensen, Eric M

    2016-01-01

    Background Chronic pain is common, costly, and leads to significant morbidity in older adults, yet we have limited data on medication safety. We sought to evaluate the association of incident High Risk Medication in the Elderly (HRME) with mortality, emergency department (ED) or hospital care among older adults with chronic pain. Methods A retrospective Veterans Health Administration cohort study was conducted examining older Veterans with chronic pain diagnoses and use of incident HRME (opioids, skeletal muscle relaxants, antihistamines, and psychotropics). Outcomes evaluated included all-cause mortality, ED visits, or inpatient hospital care. Descriptive statistics summarized variables for the overall cohort, the chronic pain cohort, and those with and without HRME. Separate generalized linear mixed-effect regression models were used to examine the association of incident HRME on each outcome, controlling for potential confounders. Results Among 1,807,404 Veterans who received VA care in 2005–2006, 584,066 (32.3%) had chronic pain; 45,945 Veterans with chronic pain (7.9%) had incident HRME exposure. The strongest significant associations of incident HRME were for: high-risk opioids with all-cause hospitalizations (OR 2.08, 95%CI 1.95–2.23); skeletal muscle relaxants with all-cause ED visits (OR 2.62, 95%CI 2.52–2.73) and mortality (OR 0.80, 95%CI 0.74–0.86); antihistamines with all-cause ED visits (OR 2.82 95%CI 2.72–2.95); and psychotropics with all-cause hospitalizations (OR 2.15, 95%CI 1.96–2.35). Conclusions Our data indicate that incident HRME is associated with clinically important adverse outcomes in older Veterans with chronic pain and highlight the importance of being judicious with prescribing certain classes of drugs in this vulnerable population. PMID:26418380

  2. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells.

    PubMed

    Person, Rachel J; Tokar, Erik J; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N Olive; Waalkes, Michael P

    2013-12-01

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. © 2013.

  3. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    PubMed Central

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Olive Ngalame, Ntube N.; Waalkes, Michael P.

    2013-01-01

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell’s ability to adapt to chronic cadmium exposure. PMID:23811327

  4. Spatio-temporal modeling of chronic PM 10 exposure for the Nurses' Health Study

    NASA Astrophysics Data System (ADS)

    Yanosky, Jeff D.; Paciorek, Christopher J.; Schwartz, Joel; Laden, Francine; Puett, Robin; Suh, Helen H.

    2008-06-01

    Chronic epidemiological studies of airborne particulate matter (PM) have typically characterized the chronic PM exposures of their study populations using city- or county-wide ambient concentrations, which limit the studies to areas where nearby monitoring data are available and which ignore within-city spatial gradients in ambient PM concentrations. To provide more spatially refined and precise chronic exposure measures, we used a Geographic Information System (GIS)-based spatial smoothing model to predict monthly outdoor PM10 concentrations in the northeastern and midwestern United States. This model included monthly smooth spatial terms and smooth regression terms of GIS-derived and meteorological predictors. Using cross-validation and other pre-specified selection criteria, terms for distance to road by road class, urban land use, block group and county population density, point- and area-source PM10 emissions, elevation, wind speed, and precipitation were found to be important determinants of PM10 concentrations and were included in the final model. Final model performance was strong (cross-validation R2=0.62), with little bias (-0.4 μg m-3) and high precision (6.4 μg m-3). The final model (with monthly spatial terms) performed better than a model with seasonal spatial terms (cross-validation R2=0.54). The addition of GIS-derived and meteorological predictors improved predictive performance over spatial smoothing (cross-validation R2=0.51) or inverse distance weighted interpolation (cross-validation R2=0.29) methods alone and increased the spatial resolution of predictions. The model performed well in both rural and urban areas, across seasons, and across the entire time period. The strong model performance demonstrates its suitability as a means to estimate individual-specific chronic PM10 exposures for large populations.

  5. Spatio-temporal modeling of chronic PM10 exposure for the Nurses' Health Study.

    PubMed

    Yanosky, Jeff D; Paciorek, Christopher J; Schwartz, Joel; Laden, Francine; Puett, Robin; Suh, Helen H

    2008-06-01

    Chronic epidemiological studies of airborne particulate matter (PM) have typically characterized the chronic PM exposures of their study populations using city- or countywide ambient concentrations, which limit the studies to areas where nearby monitoring data are available and which ignore within-city spatial gradients in ambient PM concentrations. To provide more spatially refined and precise chronic exposure measures, we used a Geographic Information System (GIS)-based spatial smoothing model to predict monthly outdoor PM(10) concentrations in the northeastern and midwestern United States. This model included monthly smooth spatial terms and smooth regression terms of GIS-derived and meteorological predictors. Using cross-validation and other pre-specified selection criteria, terms for distance to road by road class, urban land use, block group and county population density, point- and area-source PM(10) emissions, elevation, wind speed, and precipitation were found to be important determinants of PM(10) concentrations and were included in the final model. Final model performance was strong (cross-validation R(2)=0.62), with little bias (-0.4 mug m(-3)) and high precision (6.4 mug m(-3)). The final model (with monthly spatial terms) performed better than a model with seasonal spatial terms (cross-validation R(2)=0.54). The addition of GIS-derived and meteorological predictors improved predictive performance over spatial smoothing (cross-validation R(2)=0.51) or inverse distance weighted interpolation (cross-validation R(2)=0.29) methods alone and increased the spatial resolution of predictions. The model performed well in both rural and urban areas, across seasons, and across the entire time period. The strong model performance demonstrates its suitability as a means to estimate individual-specific chronic PM(10) exposures for large populations.

  6. DEMOGRAPHIC AND HISTORICAL FINDINGS, INCLUDING EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE, IN DOGS WITH CHRONIC COUGH

    PubMed Central

    Hawkins, Eleanor C.; Clay, Latoya D.; Bradley, Julie M.; Davidian, Marie

    2013-01-01

    Background Controlled studies investigating risk factors for the common presenting problem of chronic cough in dogs are lacking. Hypothesis/Objectives To identify demographic and historical factors associated with chronic cough in dogs, and associations between the characteristics of cough and diagnosis. Animals Dogs were patients of an academic internal medicine referral service. Coughing dogs had a duration of cough ≥ 2 months (n=115). Control dogs had presenting problems other than cough (n=104). Methods Owners completed written questionnaires. Demographic information and diagnoses were obtained from medical records. Demographic and historical data were compared between coughing and control dogs. Demographic data and exposure to environmental tobacco smoke (ETS) also were compared with hospital accessions and adult smoking rates, respectively. Characteristics of cough were compared among diagnoses. Results Most coughing dogs had a diagnosis of large airway disease (n=88; 77%). Tracheobronchomalacia was diagnosed in 59 dogs (51%), including 79% of toy breed dogs. Demographic risk factors included older age, smaller body weight, and being toy breed (p<0.001). No association was found between coughing and month (p=0.239) or season (p=0.414) of presentation. Exposure to ETS was not confirmed to be a risk factor (p=0.243). No historical description of cough was unique to a particular diagnosis. Conclusions and clincal importance Associations with age, size, and toy breeds were strong. Tracheobronchomalacia is frequent in dogs with chronic cough, but descriptions of cough should be used cautiously in prioritizing differential diagnoses. The association between exposure to ETS and chronic cough deserves additional study. PMID:20492480

  7. Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure.

    PubMed

    Wang, Jie; Du, Hongying; Jiang, Lihong; Ma, Xiaoxian; de Graaf, Robin A; Behar, Kevin L; Mason, Graeme F

    2013-08-27

    It has been reported that chronic and acute alcohol exposure decreases cerebral glucose metabolism and increases acetate oxidation. However, it remains unknown how much ethanol the living brain can oxidize directly and whether such a process would be affected by alcohol exposure. The questions have implications for reward, oxidative damage, and long-term adaptation to drinking. One group of adult male Sprague-Dawley rats was treated with ethanol vapor and the other given room air. After 3 wk the rats received i.v. [2-(13)C]ethanol and [1, 2-(13)C2]acetate for 2 h, and then the brain was fixed, removed, and divided into neocortex and subcortical tissues for measurement of (13)C isotopic labeling of glutamate and glutamine by magnetic resonance spectroscopy. Ethanol oxidation was seen to occur both in the cortex and the subcortex. In ethanol-naïve rats, cortical oxidation of ethanol occurred at rates of 0.017 ± 0.002 µmol/min/g in astroglia and 0.014 ± 0.003 µmol/min/g in neurons, and chronic alcohol exposure increased the astroglial ethanol oxidation to 0.028 ± 0.002 µmol/min/g (P = 0.001) with an insignificant effect on neuronal ethanol oxidation. Compared with published rates of overall oxidative metabolism in astroglia and neurons, ethanol provided 12.3 ± 1.4% of cortical astroglial oxidation in ethanol-naïve rats and 20.2 ± 1.5% in ethanol-treated rats. For cortical astroglia and neurons combined, the ethanol oxidation for naïve and treated rats was 3.2 ± 0.3% and 3.8 ± 0.2% of total oxidation, respectively. (13)C labeling from subcortical oxidation of ethanol was similar to that seen in cortex but was not affected by chronic ethanol exposure.

  8. Investigation of rare chronic lipoid pneumonia associated with occupational exposure to paraffin aerosol

    PubMed Central

    Han, Chenghong; Liu, Lihai; Du, Shiping; Mei, Jianhua; Huang, Ling; Chen, Min; Lei, Yongliang; Qian, Junwen; Luo, Jianyong; Zhang, Meibian

    2016-01-01

    Objectives: Occupational exposure to paraffin is an infrequent cause of lipoid pneumonia (LP) and related data are scare. We investigated the possible relationship between three rare cases of chronic LP and occupational exposure to paraffin aerosol in an iron foundry. Methods: The three cases of LP and their workplaces were investigated using data from field investigations, air monitoring, pulmonary radiological examinations, cell staining, and lung biopsies. Results: The patients had long-term occupational exposure to paraffin. X-ray diffraction testing revealed that the raw material from the workshop was paraffin crystal. The air concentrations of paraffin aerosol in workplaces were significantly higher than outdoor background levels. Small diffuse and miliary shadows with unclear edges were observed throughout the whole lungs via radiography. Computed tomography revealed diffuse punctate nodules and a high density of stripe-like shadows in both lungs (ground-glass opacity in a lower lobe, and a mass-like lesion and high translucent area near the bottom of the lung). Lipid-laden macrophages were found in the sputum and bronchial lavage. A broadened alveolar septum and local focal fibrosis were also discovered via lung biopsy. The inflammatory reaction in the lung tissues appeared to resolve over time. Conclusions: These three rare cases of chronic LP in workers during molding and repair processes were associated with occupational paraffin aerosol exposure. Therefore, primary prevention is essential for molding or repairing workers in the iron foundry, and a differential diagnosis of occupational chronic LP (vs. pneumoconiosis) should be considered when treating these workers. PMID:27488044

  9. Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat

    DTIC Science & Technology

    2014-05-10

    AFRL-AFOSR-UK-TR-2014-0032 Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver...TITLE AND SUBTITLE Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver of Sprague-Dawley rat 5a...Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Nanoparticles (NPs) are, by definition

  10. Responses of subjects with chronic obstructive pulmonary disease after exposures to 0. 3 ppm ozone

    SciTech Connect

    Kehrl, H.R.; Hazucha, M.J.; Solic, J.J.; Bromberg, P.A.

    1985-05-01

    The authors previously reported that the respiratory mechanics of intermittently exercising persons with chronic obstructive pulmonary disease (COPD) were unaffected by a 2-h exposure to 0.2 ppm ozone. Employing a single-blind, cross-over design protocol, 13 white men with nonreversible COPD (9 current smokers; mean FEV1/FVC, 56%) were randomly exposed on 2 consecutive days for 2 h to air and 0.3 ppm ozone. During exposures, subjects exercised (minute ventilation, 26.4 +/- 3.0 L/min) for 7.5 min every 30 min; ventilation and gas exchange measured during exercise showed no difference between exposure days. Pulmonary function tests (spirometry, body plethysmography) obtained before and after exposures were unchanged on the air day. On the ozone day the mean airway resistance and specific airway resistance showed the largest (25 and 22%) changes (p = 0.086 and 0.058, respectively). Arterial oxygen saturation (SaO/sub 2/) obtained in 8 subjects during the last exercise interval showed a mean decrement of 0.95% on the ozone exposure day; this change did not attain significance (p = 0.074). Nevertheless, arterial oxygen desaturation may be a true consequence of low-level ozone exposure in this compromised patient group. As normal subjects undergoing exposures to ozone with slightly higher exercise intensities show a threshold for changes in their respiratory mechanics at approximately 0.3 ppm, these data indicate that persons with COPD are not unduly sensitive to the effects of low-level ozone exposure.

  11. When are burns not accidental?

    PubMed

    Hobbs, C J

    1986-04-01

    One hundred and ninety five children aged up to 6 years with burns and scalds (30 non-accidental and 165 accidental) were studied retrospectively. The history, presentation, and other typical injuries assisted the diagnosis of abuse. Scalds accounted for 81% of accidents and 25% of the cases of abuse, and burns for 17% and 44%, respectively. Scalds usually followed spillage from kitchen containers in accidents and forced tap water immersion in cases of abuse. Burns in cases of both accidents and abuse resulted from contact with a wide range of household appliances, including room heaters. Attention is drawn to the back of the hand as an important site in cases of abuse, as well as the legs, buttocks, and feet. It is speculated that the low level of reporting of this form of child abuse reflects failure of diagnosis.

  12. [Management of severe accidental hypothermia].

    PubMed

    Avellanas, M L; Ricart, A; Botella, J; Mengelle, F; Soteras, I; Veres, T; Vidal, M

    2012-04-01

    Accidental hypothermia is an environmental condition with basic principles of classification and resuscitation that apply to mountain, sea or urban scenarios. Along with coagulopathy and acidosis, hypothermia belongs to the lethal triad of trauma victims requiring critical care. A customized healthcare chain is involved in its management, extending from on site assistance to intensive care, cardiac surgery and/or the extracorporeal circulation protocols. A good classification of the degree of hypothermia preceding admission contributes to improve management and avoids inappropriate referrals between hospitals. The most important issue is to admit hypothermia victims in asystolia or ventricular fibrillation to those hospitals equipped with the medical technology which these special clinical scenarios require. This study attempts to establish the foundations for optimum management of accidental hypothermia from first emergency care on site to treatment in hospital including, resuscitation and rewarming with extracorporeal circulation. Copyright © 2011 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  13. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    SciTech Connect

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P.

    2013-12-01

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the relationship

  14. 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.

  15. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice*

    PubMed Central

    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. PMID:25559957

  16. Effect of chronic exposure to zinc in young spats of the Pacific oyster (Crassostrea gigas).

    PubMed

    Devos, Alexandre; Voiseux, Claire; Caplat, Christelle; Fievet, Bruno

    2012-12-01

    The marine coastal environment is exposed to a mixture of environmental pollutants of anthropogenic origin, resulting in chronic low concentrations of contaminants. As a consequence, most coastal marine species are exposed to low doses of such pollutants during their entire life. Many marine species live for years in their natural environment, whereas they do not under laboratory exposure conditions. Using early stages of development in laboratory work allows animals to be chronically exposed from an early age over a reasonable experiment period. In the present study, the authors investigated the effect of chronic exposure to zinc in spats of the Pacific oyster (Crassostrea gigas), from metamorphosis up to 10 weeks. The authors investigated integrated biological endpoints that would account for the apparent general health of the animals as well as molecular markers showing more subtle effects that could potentially go unnoticed at a biologically integrated level. The authors measured in parallel both growth and the transcriptional level of target stress genes. Growth was monitored by image analysis of large samples to avoid high variability and ensure statistical robustness. A dose-response relationship was derived from growth data, yielding a median effective concentration (EC50) of 7.55 µM. Stress genes selected on the basis of available RNA sequences in C. gigas included genes involved in chaperone proteins, oxidative stress, detoxification, and cell cycle regulation. Out of nine stress target genes, only metallothionein displayed overexpression in response to high levels of zinc.

  17. Chronic exposure to aluminum and risk of Alzheimer's disease: A meta-analysis.

    PubMed

    Wang, Zengjin; Wei, Xiaomin; Yang, Junlin; Suo, Jinning; Chen, Jingyi; Liu, Xianchen; Zhao, Xiulan

    2016-01-01

    A meta-analysis was performed to investigate whether chronic exposure to aluminum (Al) is associated with increased risk of Alzheimer's disease (AD). Eight cohort and case-control studies (with a total of 10567 individuals) that met inclusion criteria for the meta-analysis were selected after a thorough literature review of PubMed, Web of Knowledge, Elsevier ScienceDirect and Springer databases up to June, 2015. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. Q test and I(2) statistic were used to examine heterogeneity between selected studies. The overall odds ratio (OR) was calculated using a fixed-effect model because no significant heterogeneity between studies was found. No publication bias was observed based on a funnel plot and Egger's test. Results showed that individuals chronically exposed to Al were 71% more likely to develop AD (OR: 1.71, 95% confidence interval (CI), 1.35-2.18). The finding suggests that chronic Al exposure is associated with increased risk of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Diffuse parenchymal lung disease in a case of chronic arsenic exposure

    PubMed Central

    Bhattacharya, Somnath; Dey, Atin; Saha, Sayantan; Kar, Saurav

    2016-01-01

    A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD). Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date. PMID:27625453

  19. [Accidental poisoning in the home].

    PubMed

    Lindblad, B E; Terkelsen, C J

    1989-09-25

    During a period of one year, a total of 79 cases of accidental poisoning were registered prospectively in the County Hospital in Aarhus and the City Hospital in Randers. The female/male ratio was 1/1.5. The incidence in children aged 0-14 years of age was 13 per 10,000. In Denmark as a whole, a total of 1,300 cases of accidental poisoning were estimated to occur during a period of one year. Sixty-four (81%) of the accidents occurred in small children aged 0-4 years. Twenty-five patients (32%) were hospitalized. The average duration of hospitalization was 2.4 days (1-4 days) and 84% of the inpatients were aged 0-4 years. The survey revealed that 27 case of accidental poisoning were due to medicine, 20 to organic solvents, eight to chemicals, 22 to poison and two to asphyxiation. It is concluded that the special legal regulations about packing and labelling are not sufficient when storage of the potential poison is not safe enough.

  20. The impairment of learning and memory and synaptic loss in mouse after chronic nitrite exposure.

    PubMed

    Chen, Yongfang; Cui, Zhanjun; Wang, Lai; Liu, Hongliang; Fan, Wenjuan; Deng, Jinbo; Deng, Jiexin

    2016-12-01

    The objective of this study is to understand the impairment of learning and memory in mouse after chronic nitrite exposure. The animal model of nitrite exposure in mouse was created with the daily intubation of nitrite in adult healthy male mice for 3 months. Furthermore, the mouse's learning and memory abilities were tested with Morris water maze, and the expression of Synaptophysin and γ-Synuclein was visualized with immunocytochemistry and Western blot. Our results showed that nitrite exposure significantly prolonged the escape latency period (ELP) and decreased the values of the frequency across platform (FAP) as well as the accumulative time in target quadrant (ATITQ) compared to control, in dose-dependent manner. In addition, after nitrite exposure, synaptophysin (SYN) positive buttons in the visual cortex was reduced, in contrast the increase of γ-synuclein positive cells. The results above were supported by Western blot as well. We conclude that nitrite exposure could lead to a decline in mice's learning and memory. The overexpression of γ-synuclein contributed to the synaptic loss, which is most likely the cause of learning and memory impairment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1720-1730, 2016. © 2015 Wiley Periodicals, Inc.

  1. The impairment of learning and memory and synaptic loss in mouse after chronic nitrite exposure

    PubMed Central

    Chen, Yongfang; Cui, Zhanjun; Wang, Lai; Liu, Hongliang; Fan, Wenjuan

    2015-01-01

    ABSTRACT The objective of this study is to understand the impairment of learning and memory in mouse after chronic nitrite exposure. The animal model of nitrite exposure in mouse was created with the daily intubation of nitrite in adult healthy male mice for 3 months. Furthermore, the mouse's learning and memory abilities were tested with Morris water maze, and the expression of Synaptophysin and γ‐Synuclein was visualized with immunocytochemistry and Western blot. Our results showed that nitrite exposure significantly prolonged the escape latency period (ELP) and decreased the values of the frequency across platform (FAP) as well as the accumulative time in target quadrant (ATITQ) compared to control, in dose‐dependent manner. In addition, after nitrite exposure, synaptophysin (SYN) positive buttons in the visual cortex was reduced, in contrast the increase of γ‐synuclein positive cells. The results above were supported by Western blot as well. We conclude that nitrite exposure could lead to a decline in mice's learning and memory. The overexpression of γ‐synuclein contributed to the synaptic loss, which is most likely the cause of learning and memory impairment. © 2015 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc. Environ Toxicol 31: 1720–1730, 2016. PMID:26218639

  2. Effects of chronic carbon monoxide exposure on fetal growth and development in mice.

    PubMed

    Venditti, Carolina C; Casselman, Richard; Smith, Graeme N

    2011-12-14

    Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

  3. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

    NASA Astrophysics Data System (ADS)

    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

    2016-10-01

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  4. Chronic mercury exposure impairs the sympathovagal control of the rat heart.

    PubMed

    Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

    2016-11-01

    Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

  5. Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity.

    PubMed

    Maskey, Dhiraj; Pradhan, Jonu; Aryal, Bijay; Lee, Chang-Min; Choi, In-Young; Park, Ki-Sup; Kim, Seok Bae; Kim, Hyung Gun; Kim, Myeung Ju

    2010-07-30

    Exponential interindividual handling in wireless communication system has raised possible doubts in the biological aspects of radiofrequency (RF) exposure on human brain owing to its close proximity to the mobile phone. In the nervous system, calcium (Ca(2+)) plays a critical role in releasing neurotransmitters, generating action potential and membrane integrity. Alterations in intracellular Ca(2+) concentration trigger aberrant synaptic action or cause neuronal apoptosis, which may exert an influence on the cellular pathology for learning and memory in the hippocampus. Calcium binding proteins like calbindin D28-K (CB) is responsible for the maintaining and controlling Ca(2+) homeostasis. Therefore, in the present study, we investigated the effect of RF exposure on rat hippocampus at 835 MHz with low energy (specific absorption rate: SAR=1.6 W/kg) for 3 months by using both CB and glial fibrillary acidic protein (GFAP) specific antibodies by immunohistochemical method. Decrease in CB immunoreactivity (IR) was noted in exposed (E1.6) group with loss of interneurons and pyramidal cells in CA1 area and loss of granule cells. Also, an overall increase in GFAP IR was observed in the hippocampus of E1.6. By TUNEL assay, apoptotic cells were detected in the CA1, CA3 areas and dentate gyrus of hippocampus, which reflects that chronic RF exposure may affect the cell viability. In addition, the increase of GFAP IR due to RF exposure could be well suited with the feature of reactive astrocytosis, which is an abnormal increase in the number of astrocytes due to the loss of nearby neurons. Chronic RF exposure to the rat brain suggested that the decrease of CB IR accompanying apoptosis and increase of GFAP IR might be morphological parameters in the hippocampus damages.

  6. Transient and persistent metabolomic changes in plasma following chronic cigarette smoke exposure in a mouse model.

    PubMed

    Cruickshank-Quinn, Charmion I; Mahaffey, Spencer; Justice, Matthew J; Hughes, Grant; Armstrong, Michael; Bowler, Russell P; Reisdorph, Richard; Petrache, Irina; Reisdorph, Nichole

    2014-01-01

    Cigarette smoke exposure is linked to the development of a variety of chronic lung and systemic diseases in susceptible individuals. Metabolomics approaches may aid in defining disease phenotypes, may help predict responses to treatment, and could identify biomarkers of risk for developing disease. Using a mouse model of chronic cigarette smoke exposure sufficient to cause mild emphysema, we investigated whether cigarette smoke induces distinct metabolic profiles and determined their persistence following smoking cessation. Metabolites were extracted from plasma and fractionated based on chemical class using liquid-liquid and solid-phase extraction prior to performing liquid chromatography mass spectrometry-based metabolomics. Metabolites were evaluated for statistically significant differences among group means (p-value≤0.05) and fold change ≥1.5). Cigarette smoke exposure was associated with significant differences in amino acid, purine, lipid, fatty acid, and steroid metabolite levels compared to air exposed animals. Whereas 60% of the metabolite changes were reversible, 40% of metabolites remained persistently altered even following 2 months of smoking cessation, including nicotine metabolites. Validation of metabolite species and translation of these findings to human plasma metabolite signatures induced by cigarette smoking may lead to the discovery of biomarkers or pathogenic pathways of smoking-induced disease.

  7. Transient and Persistent Metabolomic Changes in Plasma following Chronic Cigarette Smoke Exposure in a Mouse Model

    PubMed Central

    Cruickshank-Quinn, Charmion I.; Mahaffey, Spencer; Justice, Matthew J.; Hughes, Grant; Armstrong, Michael; Bowler, Russell P.; Reisdorph, Richard; Petrache, Irina; Reisdorph, Nichole

    2014-01-01

    Cigarette smoke exposure is linked to the development of a variety of chronic lung and systemic diseases in susceptible individuals. Metabolomics approaches may aid in defining disease phenotypes, may help predict responses to treatment, and could identify biomarkers of risk for developing disease. Using a mouse model of chronic cigarette smoke exposure sufficient to cause mild emphysema, we investigated whether cigarette smoke induces distinct metabolic profiles and determined their persistence following smoking cessation. Metabolites were extracted from plasma and fractionated based on chemical class using liquid-liquid and solid-phase extraction prior to performing liquid chromatography mass spectrometry-based metabolomics. Metabolites were evaluated for statistically significant differences among group means (p-value≤0.05) and fold change ≥1.5). Cigarette smoke exposure was associated with significant differences in amino acid, purine, lipid, fatty acid, and steroid metabolite levels compared to air exposed animals. Whereas 60% of the metabolite changes were reversible, 40% of metabolites remained persistently altered even following 2 months of smoking cessation, including nicotine metabolites. Validation of metabolite species and translation of these findings to human plasma metabolite signatures induced by cigarette smoking may lead to the discovery of biomarkers or pathogenic pathways of smoking-induced disease. PMID:25007263

  8. Chronic exposures and male fertility: the impacts of environment, diet, and drug use on spermatogenesis.

    PubMed

    Gabrielsen, J S; Tanrikut, C

    2016-07-01

    Several recent studies have suggested that sperm concentrations and semen quality have been decreasing over the past several decades in many areas of the world. The etiology of these decreases is currently unknown. Acute events can have significant impacts on spermatogenesis and are often readily identified during the male fertility evaluation. The majority of male factor infertility, however, is idiopathic. Chronic, low-dose exposures to chemicals and nutrients are more difficult to identify, but are extremely prevalent. These exposures have been shown to have dramatic effects on both individual and community health and interest in the cumulative and synergistic impacts of such agents on spermatogenesis has been increasing. While our understanding of these potential hazards is evolving, it is clear that they may significantly influence male reproductive potential. This review explores the literature related to effects of chronic exposures from drug use, dietary intake, and the environment on spermatogenesis in humans and animals. © 2016 American Society of Andrology and European Academy of Andrology.

  9. Alteration of the behavioral effects of nicotine by chronic caffeine exposure.

    PubMed

    Tanda, G; Goldberg, S R

    2000-05-01

    The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Some epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the effects of nicotine. This paper reviews various aspects of the pharmacology of caffeine and nicotine, in humans and experimental animals, important for the understanding of the interactions between these drugs. In particular, recent experiments are reviewed in which chronic exposure to caffeine in the drinking water of rats facilitated acquisition of self-adminstration behavior, enhanced nicotine-induced increases in dopamine levels in the shell of the nucleus accumbens and altered the dopaminergic component of a nicotine discrimination. These studies provide evidence that the rewarding and subjective properties of nicotine can be changed by chronic caffeine exposure and indicate that caffeine exposure may be an important environmental factor in shaping and maintaining tobacco smoking.

  10. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice.

    PubMed

    Cai, Ping; König, Rolf; Boor, Paul J; Kondraganti, Shakuntala; Kaphalia, Bhupendra S; Khan, M Firoze; Ansari, G A S

    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 infiltration 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.

  11. Chronic exposure to morphine decreases the expression of EAAT3 via opioid receptors in hippocampal neurons.

    PubMed

    Guo, Mingyan; Cao, Dexiong; Zhu, Siyu; Fu, Ganglan; Wu, Qiang; Liang, Jianjun; Cao, Minghui

    2015-12-02

    Alterations in glutamate transporter expression are closely related to opiate addition behavior, but the role of opioid receptors is unclear. In this study, we used primary cultures of hippocampal neurons from neonatal rats to study the effects of chronic exposure to morphine on excitatory amino acid transporter 3 (EAAT3) expression and the roles of µ opioid receptor (MOR), δ opioid receptor (DOR), and κ opioid receptor (KOR) in the morphine-dependent alterations in EAAT3 expression. The results showed that the EAAT3 protein and mRNA expression levels decreased significantly after chronic exposure to morphine (10μmol/L) for 48h, whereas the concentration of extracellular glutamate increased. In addition, we found that both the MOR inhibitor CTOP and the DOR inhibitor naltrindole could reverse the decreased expression of EAAT3 after exposure to morphine, whereas the MOR activator DAMGO and the DOR activator DPDPE significantly decreased EAAT3 expression. The KOR inhibitor had no effect on the expression of EAAT3, whereas its activator increased EAAT3 expression. These results suggest that the down-regulation of morphine-dependent EAAT3 expression in primary rat hippocampal cultures may be mediated by MOR and DOR and that KOR may not contribute significantly to this effect.

  12. Chronic Exposure Effects of Silver Nanoparticles on Stream Microbial Decomposer Communities and Ecosystem Functions.

    PubMed

    Tlili, Ahmed; Jabiol, Jérémy; Behra, Renata; Gil-Allué, Carmen; Gessner, Mark O

    2017-02-21

    With the accelerated use of silver nanoparticles (AgNP) in commercial products, streams will increasingly serve as recipients of, and repositories for, AgNP. This raises concerns about the potential toxicity of these nanomaterials in the environment. Here we aimed to assess the impacts of chronic AgNP exposure on the metabolic activities and community structure of fungal and bacterial plant litter decomposers as central players in stream ecosystems. Minimal variation in the size and surface charge of AgNP indicated that nanoparticles were rather stable during the experiment. Five days of exposure to 0.05 and 0.5 μM AgNP in microcosms shifted bacterial community structure but had no effect on a suite of microbial metabolic activities, despite silver accumulation in the decomposing leaf litter. After 25 days, however, a broad range of microbial endpoints, as well as rates of litter decomposition, were strongly affected. Declines matched with the total silver concentration in the leaves and were accompanied by changes in fungal and bacterial community structure. These results highlight a distinct sensitivity of litter-associated microbial communities in streams to chronic AgNP exposure, with effects on both microbial functions and community structure resulting in notable ecosystem consequences through impacts on litter decomposition and further biogeochemical processes.

  13. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    SciTech Connect

    Cai Ping; Koenig, Rolf; Boor, Paul J.; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

    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 infiltration 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.

  14. Metabolic and histopathological alterations in the marine bivalve Mytilus galloprovincialis induced by chronic exposure to acrylamide.

    PubMed

    Larguinho, Miguel; Cordeiro, Ana; Diniz, Mário S; Costa, Pedro M; Baptista, Pedro V

    2014-11-01

    Although the neurotoxic and genotoxic potential of acrylamide has been established in freshwater fish, the full breadth of the toxicological consequences induced by this xenobiotic has not yet been disclosed, particularly in aquatic invertebrates. To assess the effects of acrylamide on a bivalve model, the Mediterranean mussel (Mytilus galloprovincialis), two different setups were accomplished: 1) acute exposure to several concentrations of waterborne acrylamide to determine lethality thresholds of the substance and 2) chronic exposure to more reduced acrylamide concentrations to survey phases I and II metabolic endpoints and to perform a whole-body screening for histopathological alterations. Acute toxicity was low (LC50≈400mg/L). However, mussels were responsive to prolonged exposure to chronic concentrations of waterborne acrylamide (1-10mg/L), yielding a significant increase in lipid peroxidation plus EROD and GST activities. Still, total anti-oxidant capacity was not exceeded. In addition, no neurotoxic effects could be determined through acetylcholine esterase (AChE) activity. The findings suggest aryl-hydrocarbon receptor (Ahr)-dependent responses in mussels exposed to acrylamide, although reduced comparatively to vertebrates. No significant histological damage was found in digestive gland or gills but female gonads endured severe necrosis and oocyte atresia. Altogether, the results indicate that acrylamide may induce gonadotoxicity in mussels, although the subject should benefit from further research. Altogether, the findings suggest that the risk of acrylamide to aquatic animals, especially molluscs, may be underestimated. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats.

    PubMed

    Soellner, Deborah E; Grandys, Theresa; Nuñez, Joseph L

    2009-12-14

    In this report, we demonstrate that chronic prenatal exposure to a moderate dose of caffeine disrupts novel object recognition and radial arm maze behaviors in adult male and female rats. Pregnant dams were administered either tap water or 75 mg/L caffeinated tap water throughout gestation. Oral self-administration in the drinking water led to an approximate maternal intake of 10mg/kg/day, equivalent to 2-3 cups of coffee/day in humans based on a metabolic body weight conversion. In adulthood, the offspring underwent testing on novel object recognition, radial arm maze, and Morris water maze tasks. Prenatal caffeine exposure was found to impair 24-h memory retention in the novel object recognition task and impair both working and reference memory in the radial arm maze. However, prenatal caffeine exposure did not alter Morris water maze performance in either a simple water maze procedure or in an advanced water maze procedure that included reversal and working memory paradigms. These findings demonstrate that chronic oral intake of caffeine throughout gestation can alter adult cognitive behaviors in rats.

  16. Vascular Dysfunction in Patients with Chronic Arsenosis Can Be Reversed by Reduction of Arsenic Exposure

    PubMed Central

    Pi, Jingbo; Yamauchi, Hiroshi; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Fujimoto, Wataru; Iso, Hiroyasu; Cui, Renzhe; Waalkes, Michael P.; Kumagai, Yoshito

    2005-01-01

    Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3′,5′-monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean ± SEM: male, 37.0 ± 6.1; female, 37.2 ± 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 ± 5.6; female, 70.6 ± 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure. PMID:15743725

  17. Vascular dysfunction in patients with chronic arsenosis can be reversed by reduction of arsenic exposure.

    PubMed

    Pi, Jingbo; Yamauchi, Hiroshi; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Fujimoto, Wataru; Iso, Hiroyasu; Cui, Renzhe; Waalkes, Michael P; Kumagai, Yoshito

    2005-03-01

    Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3 ,5 -monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean +/- SEM: male, 37.0 +/- 6.1; female, 37.2 +/- 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 +/- 5.6; female, 70.6 +/- 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure.

  18. Chronic Prenatal Caffeine Exposure Impairs Novel Object Recognition and Radial Arm Maze Behaviors in Adult Rats

    PubMed Central

    Soellner, Deborah E.; Grandys, Theresa; Nuñez, Joseph L.

    2009-01-01

    In this report, we demonstrate that chronic prenatal exposure to a moderate dose of caffeine disrupts novel object recognition and radial arm maze behaviors in adult male and female rats. Pregnant dams were administered either tap water or 75 mg/L caffeinated tap water throughout gestation. Oral self-administration in the drinking water led to an approximate maternal intake of 10 mg/kg/day, equivalent to 2–3 cups of coffee/day in humans based on a metabolic body weight conversion. In adulthood, the offspring underwent testing on novel object recognition, radial arm maze, and Morris water maze tasks. Prenatal caffeine exposure was found to impair 24-hour memory retention in the novel object recognition task and impair both working and reference memory in the radial arm maze. However, prenatal caffeine exposure did not alter Morris water maze performance in either a simple water maze procedure or in an advanced water maze procedure that included reversal and working memory paradigms. These findings demonstrate that chronic oral intake of caffeine throughout gestation can alter adult cognitive behaviors in rats. PMID:19686781

  19. Alterations induced by chronic lead exposure on the cells of circadian pacemaker of developing rats

    PubMed Central

    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Rojas, Patricia; Chávez-Saldaña, Margarita; Pérez, Oscar Gutiérrez; Montes, Sergio; Ríos, Camilo

    2011-01-01

    Lead (Pb) exposure alters the temporal organization of several physiological and behavioural processes in which the suprachiasmatic nucleus (SCN) of the hypothalamus plays a fundamental role. In this study, we evaluated the effects of chronic early Pb exposure (CePbe) on the morphology, cellular density and relative optical density (OD) in the cells of the SCN of male rats. Female Wistar rats were exposed during gestation and lactation to a Pb solution containing 320 ppm of Pb acetate through drinking water. After weaning, the pups were maintained with the same drinking water until sacrificed at 90 days of age. Pb levels in the blood, hypothalamus, hippocampus and prefrontal cortex were significantly increased in the experimental group. Chronic early Pb exposure induced a significant increase in the minor and major axes and somatic area of vasoactive intestinal polypeptide (VIP)- and vasopressin (VP)-immunoreactive neurons. The density of VIP-, VP- and glial fibrillary acidic protein (GFAP)-immunoreactive cells showed a significant decrease in the experimental group. OD analysis showed a significant increase in VIP neurons of the experimental group. The results showed that CePbe induced alterations in the cells of the SCN, as evidenced by modifications in soma morphology, cellular density and OD in circadian pacemaker cells. These findings provide a morphological and cellular basis for deficits in circadian rhythms documented in Pb-exposed animals. PMID:21324006

  20. Subjective complaints in persons under chronic low-dose exposure to lower polychlorinated biphenyls (PCBs).

    PubMed

    Broding, Horst Christoph; Schettgen, Thomas; Hillert, Andreas; Angerer, Jürgen; Göen, Thomas; Drexler, Hans

    2008-10-01

    Polychlorinated biphenyls (PCBs) have been in widespread industrial use in the 1960s and 1970s. Despite a worldwide reduction, environmental exposure remains an issue especially in contaminated buildings. Due to the ubiquitous presence and poor degradation of PCBs, public health concerns continue to exist; however, evidence on the actual health effects of chronic low-dose exposure is scanty. The objective of the present study is an assessment of subjective complaints of exposed subjects in comparison to a non-exposed control group and their inter-relation to plasma levels of PCB congeners. The plasma concentrations of PCB congeners were measured in 583 subjects who had worked for an average of 14.7+/-9.6 years in a contaminated building in Germany, and 205 control subjects working in a non-contaminated building. Subjective complaints were assessed with the 24-item 'Giessen Subjective Complaints List' (GSCL-24). The subjects under chronic low-dose exposure scored significantly higher values on all the GSCL subscales except 'stomach complaints' in comparison to the non-exposed subjects and a 'normal' sample derived from the literature. However, thorough statistical analysis revealed no correlation of symptoms and PCB congener plasma concentration; the scores on the subscale 'exhaustion were even higher in subjects with low PCB concentration. Subjects working in a PCB-contaminated building report more subjective complaints in comparison to non-exposed subjects, but the complaints are not related to current PCB plasma concentrations.

  1. Chronic intrauterine exposure to endotoxin does not alter fetal nephron number or glomerular size.

    PubMed

    Ryan, Danica; Atik, Anzari; De Matteo, Robert; Harding, Richard; Black, Mary J

    2013-11-01

    A reduced nephron endowment early in life adversely impacts on long-term functional reserve in the kidney. A recent study has shown that acute exposure to chorioamnionitis during late gestation can adversely impact on nephrogenesis. The present study aimed to examine the effects of chronic, low-dose endotoxin exposure in utero, during the period of nephrogenesis, on nephron number and glomerular size in preterm lambs. Ewes were administered either endotoxin (lipopolysaccharide; 1 mg/day) or saline at 110-133 days of gestation (term approximately 147 days) via surgically implanted osmotic minipumps within the amniotic cavity. The ewes were induced to deliver preterm at 133 days gestation and the kidneys of the lambs were analysed at 8 weeks after term-equivalent age. Nephron number per kidney was determined using a combined optical disector and fractionator stereological approach; renal corpuscle size was also measured stereologically. At 8 weeks after term-equivalent age there was no significant effect of in utero exposure to endotoxin on bodyweight or kidney weight and there were no significant differences in nephron number, nephron density or renal corpuscle volume between groups. We conclude that chronic intrauterine inflammation during the period of nephrogenesis may not adversely impact on the number of nephrons formed within the kidney or on the volume of the renal corpuscle. © 2013 Wiley Publishing Asia Pty Ltd.

  2. Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Paulin, Laura M.; Diette, Gregory B.; Blanc, Paul D.; Putcha, Nirupama; Eisner, Mark D.; Kanner, Richard E.; Belli, Andrew J.; Christenson, Stephanie; Tashkin, Donald P.; Han, MeiLan; Barr, R. Graham

    2015-01-01

    Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. Objectives: To determine the impact of occupational exposures on COPD morbidity. Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04–1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (−26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (−3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may

  3. The role of environmental tobacco exposure and Helicobacter pylori infection in the risk of chronic tonsillitis in children.

    PubMed

    Li'e, Chen; Juan, Che; Dongying, Jiang; Guiling, Feng; Tihua, Zheng; Yanfei, Wang

    2017-01-01

    Helicobacter pylori (H. pylori) is a chronic infectious pathogen with high prevalence. This study investigated the interaction between environmental tobacco exposure and H. pylori infection on the incidence of chronic tonsillitis in Chinese children. Cross-sectional study performed in an outpatient clinic in China. Pediatric patients with chronic tonsillitis were enrolled. H. pylori infection was determined according to the presence of H. pylori CagA IgG antibodies. Serum cotinine levels and environmental tobacco smoke (ETS) exposure were determined for all participants. There was no significant difference in H. pylori infection between the children with chronic tonsillitis and children free of disease, but there was a significant difference in ETS between the two groups (P = 0.011). We next studied the association between ETS and chronic tonsillitis based on H. pylori infection status. In the patients with H. pylori infection, there was a significant difference in ETS distribution between the chronic tonsillitis and control groups (P = 0.022). Taking the participants without ETS as the reference, multivariate logistic regression analysis showed that those with high ETS had higher susceptibility to chronic tonsillitis (adjusted OR = 2.33; 95% CI: 1.67-3.25; adjusted P < 0.001). However, among those without H. pylori infection, ETS did not predispose towards chronic tonsillitis. Our findings suggest that tobacco exposure should be a putative mediator risk factor to chronic tonsillitis among children with H. pylori infection.

  4. Comparison of Graded Exercise and Graded Exposure Clinical Outcomes for Patients With Chronic Low Back Pain

    PubMed Central

    George, Steven Z.; Wittmer, Virgil T.; Fillingim, Roger B.; Robinson, Michael E.

    2017-01-01

    STUDY DESIGN Quasi-experimental clinical trial. OBJECTIVES This study compared outcomes from graded exercise and graded exposure activity prescriptions for patients participating in a multidisciplinary rehabilitation program for chronic low back pain. Our primary purpose was to investigate whether pain and disability outcomes differed based on treatment received (graded exercise or graded exposure). Our secondary purpose was to investigate if changes in selected psychological factors were associated with pain and disability outcomes. BACKGROUND Behavioral interventions have been advocated for decreasing pain and disability from low back pain, yet relatively few comparative studies have been reported in the literature. METHODS Consecutive sample with chronic low back pain recruited over a 16-month period from an outpatient chronic pain clinic. Patients received physical therapy supplemented with either graded exercise (n = 15) or graded exposure (n = 18) principles. Graded exercise included general therapeutic activities and was progressed with a quota-based system. Graded exposure included specific activities that were feared due to back pain and was progressed with a hierarchical exposure paradigm. Psychological measures were pain-related fear (Fear-Avoidance Beliefs Questionnaire, Tampa Scale for Kinesiophobia, Fear of Pain Questionnaire), pain catastrophizing (Coping Strategies Questionnaire), and depressive symptoms (Beck Depression Inventory). Primary outcome measures were pain intensity (visual analog scale) and self-report of disability (modified Oswestry Disability Questionnaire). RESULTS Statistically significant improvements (P<.01) were observed for pain intensity and disability at discharge. The rate of improvement did not differ based on behavioral intervention received (P>.05 for these comparisons). Overall, 50% of patients met criterion for minimally important change for pain intensity, while 30% met this criterion for disability. Change in

  5. Use of human lung tissue for studies of structural changes associated with chronic ozone exposure: opportunities and critical issues.

    PubMed Central

    Lippmann, M

    1993-01-01

    Definitive information on the chronic effects of exposure to ozone (O3) in humans is not available. There is a strong concern that ozone could produce chronic lung damage in humans on the basis that exposures are ubiquitous at levels that produce transient symptoms, function deficits, and lung inflammation in humans and chronic lung damage in laboratory animals. Both prospective and national population surveys suggest an association between chronic O3 exposure and reduced lung function, and a pilot investigation of autopsied lungs of accident victims in Los Angeles reported an unexpectedly high incidence of disease in the centriacinar region, the lung region known to receive the highest dose of inhaled O3. This paper discusses the advantages and limitations of further studies of structural changes in human lung tissue in relation to chronic O3 exposure. The major advantages of such studies are that a) measurable effects may be related to realistic chronic exposures, b) the effects may be described quantitatively and compared directly to those obtained in chronic animal inhalation exposures, and c) evidence for chronic effects may be obtained much more rapidly than in prospective studies. The major limitations are the difficulties in obtaining sufficient reliable information on residential history, physical activity out-of-doors, and smoking and other confounding exposures to lung irritants from next of kin, and limited availability of adequate air quality data for determining ambient concentrations at places of residence and/or outdoor exercise. The paper also discusses approaches to minimizing these limitations in the design of specific studies. PMID:8206033

  6. 3,4-methylenedioxymethamphetamine (MDMA) intoxication in an infant chronically exposed to cocaine.

    PubMed

    Garcia-Algar, Oscar; López, Nuria; Bonet, Mariona; Pellegrini, Manuela; Marchei, Emilia; Pichini, Simona

    2005-08-01

    Accidental ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) was detected in an infant admitted at the Pediatric Emergency Department by drug testing in urine. Concentrations of MDMA and its principal metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) in the infant's hydrolyzed urine were 11.7 mg/L and 34.4 mg/L, respectively. Apparent febrile convulsions and cardiovascular side effects resolved within 1 day after treatment with benzodiazepines. Chronic exposure to cocaine was evidenced by segmental hair analysis. Continuous maternal denial of the presence of any drug in the household made diagnosis of accidental ingestion of MDMA and chronic exposure to cocaine problematic. Periodic clinical and laboratory follow-ups were requested to check eventual long-term effects of exposure to illicit drugs and discontinuation of the child from exposure to dangerous environments.

  7. Chronic exposure to pentachlorophenol alters thyroid hormones and thyroid hormone pathway mRNAs in zebrafish.

    PubMed

    Yu, Li-Qin; Zhao, Gao-Feng; Feng, Min; Wen, Wu; Li, Kun; Zhang, Pan-Wei; Peng, Xi; Huo, Wei-Jie; Zhou, Huai-Dong

    2014-01-01

    Pentachlorophenol (PCP) is frequently detected in the aquatic environment and has been implicated as an endocrine disruptor in fish. In the present study, 4-month-old zebrafish (Danio rerio) were exposed to 1 of 4 concentrations of PCP (0.1, 1, 9, and 27 µg/L) for 70 d. The effects of PCP exposure on plasma thyroid hormone levels, and the expression levels of selected genes, were measured in the brain and liver. The PCP exposure at 27 µg/L resulted in elevated plasma thyroxine concentrations in male and female zebrafish and depressed 3, 5, 3'-triiodothyronine concentrations in males only. In both sexes, PCP exposure resulted in decreased messenger RNA (mRNA) expression levels of thyroid-stimulating hormone β-subunit (tshβ) and thyroid hormone receptor β (trβ) in the brain, as well as increased liver levels of uridine diphosphoglucuronosyl transferase (ugt1ab) and decreased deiodinase 1 (dio1). The authors also identified several sex-specific effects of PCP exposure, including changes in mRNA levels for deiodinase 2 (dio2), cytosolic sulfotransferase (sult1 st5), and transthyretin (ttr) genes in the liver. Environmental PCP exposure also caused an increased malformation rate in offspring that received maternal exposure to PCP. The present study demonstrates that chronic exposure to environmental levels of PCP alters plasma thyroid hormone levels, as well as the expression of genes associated with thyroid hormone signaling and metabolism in the hypothalamic-pituitary-thyroid (HPT) axis and liver, resulting in abnormal zebrafish development.

  8. Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex.

    PubMed

    Kroener, Sven; Mulholland, Patrick J; New, Natasha N; Gass, Justin T; Becker, Howard C; Chandler, L Judson

    2012-01-01

    In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC.

  9. Chronic Alcohol Exposure Alters Behavioral and Synaptic Plasticity of the Rodent Prefrontal Cortex

    PubMed Central

    Kroener, Sven; Mulholland, Patrick J.; New, Natasha N.; Gass, Justin T.; Becker, Howard C.; Chandler, L. Judson

    2012-01-01

    In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC. PMID:22666364

  10. Chronic inhalation exposure of hamsters to nickel-enriched fly ash

    SciTech Connect

    Wehner, A.P.; Dagle, G.E.; Milliman, E.M.

    1981-10-01

    Hamsters were chronically exposed to approx.70 ..mu..g/liter respirable nickel-enriched fly ash (NEFA) aerosol, approx.17 ..mu..g/liter NEFA, or approx.70 ..mu..g/liter fly ash (FA) for up to 20 months. A control group received sham exposures. The NEFA particles of respirable size contained approximately 6% nickel, compared to about 0.3% for FA. Five hamsters/group were sacrificed after 4, 8, 12, or 16 months of exposure. An additional five hamsters/group were withdrawn from exposure at the same intervals for lifelong observations. Exposures to NEFA had no significant effect on body weight and life span of the animals although heavy deposits of NEFA in the lungs were demonstrated. However, lung weights of the high NEFA- and of the FA-exposed animals were significantly higher than those of the low-NEFA group and the controls, and mean lung volumes were significantly larger for the high-NEFA grop and the FA group than for the low-NEFA group and the controls. Dust was deposited (anthracosis) in the lungs of all exposed hamsters. Incidence and severity of interstitial reaction and bronchiolization were significantly higher in the dust-exposed groups than in the sham-exposed controls. The severity of anthracosis, interstitial reaction, and bronchiolization was significantly lower in the low-NEFA group than in the high-NEFA and FA groups. While two malignant primary thorax tumors were found in two hamsters of the high-NEFA group, no statistically significant carcinogenesis was observed. Of the exposure-related changes, only anthracosis decreased after withdrawal from exposure. Pulmonary nickel burdens after 20 months of exposure suggest that the pulmonary clearance rate was slower in the high-NEFA group than in the low-NEFA group.

  11. Effects of chronic exposure to radiofrequency electromagnetic fields on energy balance in developing rats.

    PubMed

    Pelletier, Amandine; Delanaud, Stéphane; Décima, Pauline; Thuroczy, Gyorgy; de Seze, René; Cerri, Matteo; Bach, Véronique; Libert, Jean-Pierre; Loos, Nathalie

    2013-05-01

    The effects of radiofrequency electromagnetic fields (RF-EMF) on the control of body energy balance in developing organisms have not been studied, despite the involvement of energy status in vital physiological functions. We examined the effects of chronic RF-EMF exposure (900 MHz, 1 V m(-1)) on the main functions involved in body energy homeostasis (feeding behaviour, sleep and thermoregulatory processes). Thirteen juvenile male Wistar rats were exposed to continuous RF-EMF for 5 weeks at 24 °C of air temperature (T a) and compared with 11 non-exposed animals. Hence, at the beginning of the 6th week of exposure, the functions were recorded at T a of 24 °C and then at 31 °C. We showed that the frequency of rapid eye movement sleep episodes was greater in the RF-EMF-exposed group, independently of T a (+42.1 % at 24 °C and +31.6 % at 31 °C). The other effects of RF-EMF exposure on several sleep parameters were dependent on T a. At 31 °C, RF-EMF-exposed animals had a significantly lower subcutaneous tail temperature (-1.21 °C) than controls at all sleep stages; this suggested peripheral vasoconstriction, which was confirmed in an experiment with the vasodilatator prazosin. Exposure to RF-EMF also increased daytime food intake (+0.22 g h(-1)). Most of the observed effects of RF-EMF exposure were dependent on T a. Exposure to RF-EMF appears to modify the functioning of vasomotor tone by acting peripherally through α-adrenoceptors. The elicited vasoconstriction may restrict body cooling, whereas energy intake increases. Our results show that RF-EMF exposure can induce energy-saving processes without strongly disturbing the overall sleep pattern.

  12. 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.

  13. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... effects of exposure to mustard gas and Lewisite. 3.316 Section 3.316 Pensions, Bonuses, and Veterans... Compensation Ratings and Evaluations; Service Connection § 3.316 Claims based on chronic effects of exposure to... establishes a nonservice-related supervening condition or event as the cause of the claimed condition (See §...

  14. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... effects of exposure to mustard gas and Lewisite. 3.316 Section 3.316 Pensions, Bonuses, and Veterans... Compensation Ratings and Evaluations; Service Connection § 3.316 Claims based on chronic effects of exposure to... establishes a nonservice-related supervening condition or event as the cause of the claimed condition (See §...

  15. Chronic progredient diffuse alveolar damage probably related to exposure to herbicides.

    PubMed

    Kayser, K; Schönberg, M; Tuengerthal, S; Vogt-Moykopf, I

    1986-01-02

    Clinical history and wedge biopsy specimen findings of a Vietnam veteran suffering from progressive severe tissue damage of lung are presented. The patient served as a soldier in defoliated areas for 2 years and developed severe chest pain and dyspnoea with chronic postnasal dripping, maxillary sinusitis and allergic asthmoid bronchitis with pronounced obstructions and eosinophilia. Recurrent onsets of symptoms over a period of 10 years led to wedge biopsies of the left upper lobe, right lower lobe and mediastinal lymph node. Histology is consistent with chronic, slightly progressive diffuse alveolar damage including moderate interstitial fibrosis. Total destruction of mediastinal lymph node with deposits of amorphous material and foreign body giant cells were noted. Histology findings and clinical course favor hypersensitivity reaction of lung and congestion of exogeneous material probably related to exposure to herbicides.

  16. Alteration of iron homeostasis following chronic exposure to manganese in rats1

    PubMed Central

    Zheng, Wei; Zhao, Qiuqu; Slavkovich, Vesna; Aschner, Michael; Graziano, Joseph H.

    2014-01-01

    Recent studies suggest that manganese-induced neurodegenerative toxicity may be partly due to its action on aconitase, which participates in cellular iron regulation and mitochondrial energy production. This study was performed to investigate whether chronic manganese exposure in rats influenced the homeostasis of iron in blood and cerebrospinal fluid (CSF). Groups of 8–10 rats received intraperitoneal injections of MnCl2 at the dose of 6 mg Mn/kg/day or equal volume of saline for 30 days. Concentrations of manganese and iron in plasma and CSF were determined by atomic absorption spectrophotometry. Rats exposed to manganese showed a greatly elevated manganese concentration in both plasma and CSF. The magnitude of increase in CSF manganese (11-fold) was equivalent to that of plasma (10-fold). Chronic manganese exposure resulted in a 32% decrease in plasma iron (p < 0.01) and no changes in plasma total iron binding capacity (TIBC). However, it increased CSF iron by 3-fold as compared to the controls (p < 0.01). Northern blot analyses of whole brain homogenates revealed a 34% increase in the expression of glutamine synthetase (p < 0.05) with unchanged metallothionein-I in manganese-intoxicated rats. When the cultured choroidal epithelial cells derived from rat choroid plexus were incubated with MnCl2 (100 µM) for four days, the expression of transferrin receptor mRNA appeared to exceed by 50% that of control (p < 0.002). The results indicate that chronic manganese exposure alters iron homeostasis possibly by expediting unidirectional influx of iron from the systemic circulation to cerebral compartment. The action appears likely to be mediated by manganese-facilitated iron transport at brain barrier systems. PMID:10375687

  17. Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats.

    PubMed

    Raval, Ami P; Sick, Justin T; Gonzalez, Gabriel J; Defazio, R Anthony; Dong, Chuanhui; Sick, Thomas J

    2012-05-23

    Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E₂) and inhibits E₂-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E₂-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-D-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16 days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30 min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80 ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E₂ in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E₂-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation. Copyright © 2012

  18. Nicotine Improves Working Memory Span Capacity in Rats Following Sub-Chronic Ketamine Exposure

    PubMed Central

    Rushforth, Samantha L; Steckler, Thomas; Shoaib, Mohammed

    2011-01-01

    Ketamine, an NMDA-receptor antagonist, produces cognitive deficits in humans in a battery of tasks involving attention and memory. Nicotine can enhance various indices of cognitive performance, including working memory span capacity measured using the odor span task (OST). This study examined the effects of a sub-chronic ketamine treatment to model cognitive deficits associated with schizophrenia, and to evaluate the effectiveness of nicotine, antipsychotic clozapine, and the novel mGlu2/3 agonist, LY404039, in restoring OST performance. Male hooded Lister rats were trained in the OST, a working memory task involving detection of a novel odor from an increasing number of presented odors until they exhibited asymptotic levels of stable performance. Sub-chronic ketamine exposure (10 and 30 mg/kg i.p. for 5 consecutive days) produced a dose-dependent impairment that was stable beyond 14 days following exposure. In one cohort, administration of graded doses of nicotine (0.025–0.1 mg/kg) acutely restored the performance in ketamine-treated animals, while significant improvements in odor span were observed in control subjects. In a second cohort of rats, acute tests with clozapine (1–10 mg/kg) and LY404039 (0.3–10 mg/kg) failed to reverse ketamine-induced deficits in doses that were observed to impair performance in the control groups. These data suggest that sub-chronic ketamine exposure in the OST presents a valuable method to examine novel treatments to restore cognitive impairments associated with neuropsychiatric disorders such as schizophrenia. Moreover, it highlights a central role for neuronal nicotinic receptors as viable targets for intervention that may be useful adjuncts to the currently prescribed anti-psychotics. PMID:21956441

  19. Nicotine improves working memory span capacity in rats following sub-chronic ketamine exposure.

    PubMed

    Rushforth, Samantha L; Steckler, Thomas; Shoaib, Mohammed

    2011-12-01

    Ketamine, an NMDA-receptor antagonist, produces cognitive deficits in humans in a battery of tasks involving attention and memory. Nicotine can enhance various indices of cognitive performance, including working memory span capacity measured using the odor span task (OST). This study examined the effects of a sub-chronic ketamine treatment to model cognitive deficits associated with schizophrenia, and to evaluate the effectiveness of nicotine, antipsychotic clozapine, and the novel mGlu2/3 agonist, LY404039, in restoring OST performance. Male hooded Lister rats were trained in the OST, a working memory task involving detection of a novel odor from an increasing number of presented odors until they exhibited asymptotic levels of stable performance. Sub-chronic ketamine exposure (10 and 30 mg/kg i.p. for 5 consecutive days) produced a dose-dependent impairment that was stable beyond 14 days following exposure. In one cohort, administration of graded doses of nicotine (0.025-0.1 mg/kg) acutely restored the performance in ketamine-treated animals, while significant improvements in odor span were observed in control subjects. In a second cohort of rats, acute tests with clozapine (1-10 mg/kg) and LY404039 (0.3-10 mg/kg) failed to reverse ketamine-induced deficits in doses that were observed to impair performance in the control groups. These data suggest that sub-chronic ketamine exposure in the OST presents a valuable method to examine novel treatments to restore cognitive impairments associated with neuropsychiatric disorders such as schizophrenia. Moreover, it highlights a central role for neuronal nicotinic receptors as viable targets for intervention that may be useful adjuncts to the currently prescribed anti-psychotics.

  20. Chronic and pulse exposure effects of silver nanoparticles on natural lake phytoplankton and zooplankton.

    PubMed

    Vincent, Jennifer L; Paterson, Michael J; Norman, Beth C; Gray, Evan P; Ranville, James F; Scott, Andrew B; Frost, Paul C; Xenopoulos, Marguerite A

    2017-02-23

    The increasing use of silver nanoparticles (AgNPs) in consumer products raises concerns regarding the environmental exposure and impact of AgNPs on natural aquatic environments. Here, we investigated the effects of environmentally relevant AgNP concentrations on the natural plankton communities using in situ enclosures. Using twelve lake enclosures, we tested the hypotheses that AgNP concentration, dosing regimen, and capping agent (poly-vinyl pyrrolidone (PVP) vs. citrate) exhibit differential effects on plankton communities. Each of the following six treatments was replicated twice: control (no AgNPs added), low, medium, and high chronic PVP treatments (PVP-capped AgNPs added continuously, with target nominal concentrations of 4, 16, and 64 μg/L, respectively), citrate treatment (citrate-capped AgNPs added continuously, target nominal concentrations of 64 μg/L), and pulse treatment (64 μg/L PVP-AgNPs added as a single dose). Although Ag accumulated in the phytoplankton, no statistically significant treatment effect was found on phytoplankton community structure or biomass. In contrast, as AgNP exposure rate increased, zooplankton abundance generally increased while biomass and species richness declined. We also observed a shift in the size structure of zooplankton communities in the chronic AgNP treatments. In the pulse treatments, zooplankton abundance and biomass were reduced suggesting short periods of high AgNP concentrations affect zooplankton communities differently than chronic exposures. We found no evidence that capping agent affected AgNP toxicity on either community. Overall, our study demonstrates variable AgNP toxicity between trophic levels with stronger AgNP effects on zooplankton. Such effects on zooplankton are troubling and indicate that AgNP contamination could affect aquatic food webs.

  1. Chronic Ethanol Exposure Effects on Vitamin D Levels Among Subjects with Alcohol Use Disorder.

    PubMed

    Ogunsakin, Olalekan; Hottor, Tete; Mehta, Ashish; Lichtveld, Maureen; McCaskill, Michael

    2016-01-01

    Vitamin D has been previously recognized to play important roles in human immune system and function. In the pulmonary system, vitamin D regulates the function of antimicrobial peptides, especially cathelicidin/LL-37. Human cathelicidin/LL-37 is a bactericidal, bacteriostatic, and antiviral endogenous peptide with protective immune functions. Chronic exposure to excessive alcohol has the potential to reduce levels of vitamin D (inactive vitamin D [25(OH)D3] and active vitamin D [1, 25(OH)2D3]) and leads to downregulation of cathelicidin/LL-37. Alcohol-mediated reduction of LL-37 may be partly responsible for increased incidence of more frequent and severe respiratory infections among subjects with alcohol use disorder (AUD). The objective of this study was to investigate the mechanisms by which alcohol exerts its influence on vitamin D metabolism. In addition, the aim was to establish associations between chronic alcohol exposures, levels of pulmonary vitamin D, and cathelicidin/LL-37 using broncho-alveolar lavage fluid samples of subjects with AUD and healthy controls. Findings from the experiment showed that levels of inactive vitamin D (25(OH)D3), active vitamin D (1, 25(OH)2D3), cathelicidin/LL-37, and CYP27B1 proteins were significantly reduced (P < 0.05) when compared with the matched healthy control group. However, CYP2E1 was elevated in all the samples examined. Chronic exposure to alcohol has the potential to reduce the levels of pulmonary vitamin D and results in subsequent downregulation of the antimicrobial peptide, LL-37, in the human pulmonary system.

  2. Chronic Ethanol Exposure Effects on Vitamin D Levels Among Subjects with Alcohol Use Disorder

    PubMed Central

    Ogunsakin, Olalekan; Hottor, Tete; Mehta, Ashish; Lichtveld, Maureen; McCaskill, Michael

    2016-01-01

    Vitamin D has been previously recognized to play important roles in human immune system and function. In the pulmonary system, vitamin D regulates the function of antimicrobial peptides, especially cathelicidin/LL-37. Human cathelicidin/LL-37 is a bactericidal, bacteriostatic, and antiviral endogenous peptide with protective immune functions. Chronic exposure to excessive alcohol has the potential to reduce levels of vitamin D (inactive vitamin D [25(OH)D3] and active vitamin D [1, 25(OH)2D3]) and leads to downregulation of cathelicidin/LL-37. Alcohol-mediated reduction of LL-37 may be partly responsible for increased incidence of more frequent and severe respiratory infections among subjects with alcohol use disorder (AUD). The objective of this study was to investigate the mechanisms by which alcohol exerts its influence on vitamin D metabolism. In addition, the aim was to establish associations between chronic alcohol exposures, levels of pulmonary vitamin D, and cathelicidin/LL-37 using broncho-alveolar lavage fluid samples of subjects with AUD and healthy controls. Findings from the experiment showed that levels of inactive vitamin D (25(OH)D3), active vitamin D (1, 25(OH)2D3), cathelicidin/LL-37, and CYP27B1 proteins were significantly reduced (P < 0.05) when compared with the matched healthy control group. However, CYP2E1 was elevated in all the samples examined. Chronic exposure to alcohol has the potential to reduce the levels of pulmonary vitamin D and results in subsequent downregulation of the antimicrobial peptide, LL-37, in the human pulmonary system. PMID:27795667

  3. Characteristics of the DINA track dosimeter for monitoring chronic neutron exposure

    SciTech Connect

    Kraitor, S.N.; Kuz'mina, T.D.; Savinskii, A.K.

    1987-09-01

    The DINA personal dosimeter included in the GNEIS beta-, gamma-, and neutron-radiation safety kit uses fission-fragment track detectors and a target containing /sup 237/Np with a /sup 10/B filter. The purpose of this paper is to derive quantitative data on the characteristics of the DINA dosimeter in the measurement of the equivalent kerma during chronic personnel exposure in neutron fields, and to evaluate whether in that situation the dosimeter can be effectively used when only the track dose value varies.

  4. [Bioeffects of chronic exposure to radiofrequency electromagnetic fields of low intensity (standardization strategy)].

    PubMed

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

    2003-01-01

    A retrospective analysis of the experimental researches on the effect of radio frequency electromagnetic fields (EMF) on human health, carried out in the USSR, is presented. The results of chronic exposure of laboratory animals to EMF have been considered. Apparently, EMF in the range of 1750-2750 MHz with power density up to 100-500 W/cm2 caused in immune globullin fractions, and a development of autoimmune processes. The changes in parameters of reproductive functions and posterity, the increase in embryo mortality were found. The standartization strategy used in the USSR and currently applied in Russia has been discussed.

  5. Pyridostigmine interaction with soman during chronic exposure in rodents. Interim report, February-November 1987

    SciTech Connect

    Kerenyi, S.Z.; Bruce, H.; Murphy, M.R.; Hartgraves, S.L.

    1988-01-01

    The effects of repeated low-level nerve agent exposure on animal performance and lethality are a major concern of USAF Medical Research. This concern has generated interest in the role that pretreatment drugs such as pyridostigmine may play during simultaneous exposure to soman. This role was investigated by recording lethality, weights, symptoms, and cholinesterase (ChE) inhibition in rats chronically exposed to 4 levels of soman (32, 39, 48 or 59 micrograms/kg/day) while simultaneously receiving 10.0 milligrams/kg/day pyridostigmine, 1.0 milligrams/kg/day pyridostigmine, or vehicle via an osmotic pump. No effect (either protective or detractive) was found in the soman-poisoned animals due to the presence or absence of pyridostigmine. However, rat blood biochemistry is different from that of the primate, warranting further study in the primate before extrapolation to man.

  6. Combat exposure is associated with cortical thickness in Veterans with a history of chronic pain.

    PubMed

    Corbo, Vincent; Salat, David H; Powell, Margaret A; Milberg, William P; McGlinchey, Regina E

    2016-03-30

    Chronic Pain (CP) has been associated with changes in gray matter integrity in the cingulate and insular cortex. However, these changes have not been studied in Veterans, despite high prevalence rates of CP and interactions with combat-derived disorders. In the current study, 54 Veterans with a history of CP and 103 Veterans without CP were recruited from the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS). Cortical thickness from structural MRI scans was determined using the FreeSurfer software package. Results showed that Veterans with CP showed a negative association between cortical thickness and levels of combat exposure in the left inferior frontal gyrus and superior parietal cortex, as well as the right rostral middle frontal gyrus, precentral and postcentral gyri and the superior temporal cortex. These findings suggest that CP may alter the relationship between cortical thickness and exposure to the stress of combat. Published by Elsevier Ireland Ltd.

  7. Further Exploration of the Links between Occupational Exposure and Chronic Obstructive Pulmonary Disease

    PubMed Central

    Blanc, Paul D.; Eisner, Mark D.; Earnest, Gillian; Trupin, Laura; Balmes, John R.; Yelin, Edward H.; Gregorich, Steven E.; Katz, Patricia P

    2009-01-01

    Objective To examine occupational risk for COPD. Methods We randomly recruited 233 subjects aged 55-75 reporting a physician's diagnosis of COPD, emphysema or chronic bronchitis. Interviews assessed cigarette smoking and longest-held job, identifying exposure to vapors, gas, dust, or fumes (VGDF). Lung function was assessed in n=138. Comparison data were derived from a sample of referents without COPD. Results VGDF was reported by 123 (53%) of 233 cases vs. 577 (34%) of 1709 referents. VGDF was associated with COPD (Odds Ratio [OR] 2.5; 95% CI 1.9 to 3.4); the population attributable fraction [PAF] was 32%. In the lung function subset, the FEV1/FVC was <70% in 79 (57%); 35 (44%) reported VGDF associated with an OR=1.6 (95% CI 0.99 to 2.6) and PAF 17%. Conclusions These data support an important role for occupational exposures in COPD. PMID:19528835

  8. Mini-Osmotic Pump Infusion Model to Investigate the Systemic Effects of Chronic Continuous Exposure to Staphylococcal Superantigen in Mice

    PubMed Central

    Krogman, Ashton L; Chowdhary, Vaidehi; Rajagopalan, Govindarajan

    2016-01-01

    Summary Staphylococcus aureus can exist as a colonizer or can cause a spectrum of diseases. S. aureus elaborates several exotoxins and the superantigens are one among them. Staphylococcal superantigens (SSAg) cause robust activation of the immune system and acute exposure to significant amounts of SSAg can be potentially lethal. However, chronic exposure to SSAg is also possible. Administering SSAg using mini-osmotic pumps may mimic chronic recurrent exposure to SSAg. This is a relatively simple and safe way to administer purified SSAg or any other toxin/agent. In this chapter, we describe the mini-osmotic pump-mediated delivery of SSAg. PMID:26676041

  9. Chronic low-level hydrogen sulfide exposure and potential effects on human health: a review of the epidemiological evidence.

    PubMed

    Lewis, R Jeffrey; Copley, G Bruce

    2015-02-01

    The effects of exposure to high concentrations of hydrogen sulfide (H2S) on human health are well known. However, the potential human health hazards posed by low-level chronic environmental H2S exposure are being debated. Accordingly, we reviewed the literature regarding the effects of chronic, environmentally-relevant H2S exposures on human health. All human observational studies using an analytical study design (e.g. cohort, cross-sectional, case-control) to evaluate chronic-duration low-level H2S exposure (approximately ≤ 10 ppm on average, for 1 year or more), were evaluated for a range of health outcomes. Respiratory symptoms in both adults and children were the most consistently reported symptoms on the increase. When reported, such effects appear to be temporary, given that there is no consistent evidence of pulmonary function deficit in either age group, among those chronically exposed to low H2S concentrations. While sparse, some data also suggest potential ocular symptoms and disorders associated with chronic ambient level H2S exposure in adults (not children), but the limited data on H2S exposures, co-exposures and/or strong odor stimulus of H2S, temper interpretation. Neurological symptoms and deficits have been reported in some studies, but the highest quality evidence, obtained using objective outcome measures and a reasonably detailed assessment of exposure, does not support a neurological-related risk in adults (only one study in children). For the other endpoints assessed (cardiovascular, reproductive and developmental, and carcinogenicity), the results were mixed and/or conflicting, but did not indicate a potential health hazard, although this literature has several major limitations, particularly with regard to exposure estimation and the ability to assess exposure-response.

  10. Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats.

    PubMed

    Morel, Lydie J; Giros, Bruno; Daugé, Valérie

    2009-10-01

    Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35-49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and mu-opioid receptors were quantified in the striatum and the mesencephalon. Chronic dronabinol exposure in AFR rats induced an increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the nucleus accumbens and the caudate-putamen nucleus, without any modification for preference to oral morphine consumption. In contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to morphine conditioning. CB1 and mu-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.

  11. Lactobacillus rhamnosus GG Effect on Behavior of Zebrafish During Chronic Ethanol Exposure

    PubMed Central

    Schneider, Ana Claudia Reis; Rico, Eduardo Pacheco; de Oliveira, Diogo Losch; Rosemberg, Denis Broock; Guizzo, Ranieli; Meurer, Fábio; da Silveira, Themis Reverbel

    2016-01-01

    Abstract Ethanol is a widely consumed drug, which acts on the central nervous system to induce behavioral alterations ranging from disinhibition to sedation. Recent studies have produced accumulating evidence for the therapeutic role of probiotic bacteria in behavior. We aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) on the behavior of adult zebrafish chronically exposed to ethanol. Adult wild-type zebrafish were randomly divided into four groups, each containing 15 fish. The following groups were formed: Control (C), received unsupplemented feed during the trial period; Probiotic (P), fed with feed supplemented with LGG; Ethanol (E), received unsupplemented feed and 0.5% of ethanol directly added to the tank water; and Probiotic+Ethanol (P+E), group under ethanol exposure (0.5%) and fed with LGG supplemented feed. After 2 weeks of exposure, the novel tank test was used to evaluate fish behavior, which was analyzed using computer-aided video tracking. LGG alone did not alter swimming behavior of the fish. Ethanol exposure led to robust behavioral effects in the form of reduced anxiety levels, as indicated by increased vertical exploration and more time spent in the upper region of the novel tank. The group exposed to ethanol and treated with LGG behaved similarly to animals exposed to ethanol alone. Taken together, these results show that zebrafish behavior was not altered by LGG per se, as seen in murine models. This was the first study to investigate the effects of a probiotic diet on behavior after a chronic ethanol exposure. PMID:26862467

  12. General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis.

    PubMed

    Maxfield, Alice Z; Korkmaz, Hakan; Gregorio, Luciano L; Busaba, Nicolas Y; Gray, Stacey T; Holbrook, Eric H; Guo, Rong; Bleier, Benjamin S

    2017-02-01

    Antibiotic use and chronic rhinosinusitis (CRS) have been independently associated with microbiome diversity depletion and opportunistic infections. This study was undertaken to investigate whether antibiotic use may be an unrecognized risk factor for developing CRS. Case-control study of 1,162 patients referred to a tertiary sinus center for a range of sinonasal disorders. Patients diagnosed with CRS according to established consensus criteria (n = 410) were assigned to the case group (273 without nasal polyps [CRSsNP], 137 with nasal polyps [CRSwNP]). Patients with all other diagnoses (n = 752) were assigned to the control group. Chronic rhinosinusitis disease severity was determined using a validated quality of life (QOL) instrument. The class, diagnosis, and timing of previous nonsinusitis-related antibiotic exposures were recorded. Results were validated using a randomized administrative data review of 452 (38.9%) of patient charts. The odds ratio of developing CRS following antibiotic exposure were calculated, as well as the impact of antibiotic use on the subsequent QOL. Antibiotic use significantly increased the odds of developing CRSsNP (odds ratio: 2.21, 95% confidence interval, 1.66-2.93, P < 0.0001) as compared to nonusers. Antibiotic exposure was significantly associated with worse CRS QOL scores (P = 0.0009) over at least the subsequent 2 years. These findings were confirmed by the administrative data review. Use of antibiotics more than doubles the odds of developing CRSsNP and is associated with a worse QOL for at least 2 years following exposure. These findings expose an unrecognized and concerning consequence of general antibiotic use. 3b. Laryngoscope, 2016 127:296-302, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Impairment of mitochondrial energy metabolism in different regions of rat brain following chronic exposure to aluminium.

    PubMed

    Kumar, Vijay; Bal, Amanjit; Gill, Kiran Dip

    2008-09-26

    The present study was designed with an aim to evaluate the effects of chronic aluminium exposure (10 mg/kg b.wt, intragastrically for 12 weeks) on mitochondrial energy metabolism in different regions of rat brain in vivo. Mitochondrial preparations from aluminium treated rats revealed significant decrease in the activity of various electron transport complexes viz. cytochrome oxidase, NADH cytochrome c reductase and succinic dehydrogenase as well, in the hippocampus region. The decrease in the activity of these respiratory complexes was also seen in the other two regions viz. corpus striatum and cerebral cortex, but to a lesser extent. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria isolated from aluminium treated rat brain regions. We also studied the spectral properties of the mitochondrial cytochromes viz. cyt a, cyt b, cyt c1, and cyt c in both control and treated rat brains. The various cytochrome levels were found to be decreased following 12 weeks of aluminium exposure. Further, these impairments in mitochondrial functions may also be responsible for the production of reactive oxygen species and impaired antioxidant defense system as observed in our study. The electron micrographs of neuronal cells depicted morphological changes in mitochondria as well as nucleus only from hippocampus and corpus striatum regions following 12 weeks exposure to aluminium. The present study thus highlights the significance of altered mitochondrial energy metabolism and increased ROS production as a result of chronic aluminium exposure in different regions of the rat brain.

  14. Spatial cognition and sexually dimorphic synaptic plasticity balance impairment in rats with chronic prenatal ethanol exposure.

    PubMed

    An, Lei; Zhang, Tao

    2013-11-01

    Prenatal ethanol exposure can lead to long-lasting impairments in the ability of rats to process spatial information, as well as produce long-lasting deficits in long-term potentiation (LTP), a biological model of learning and memory processing. The present study aimed to examine the sexually dimorphic effects of chronic prenatal ethanol exposure (CPEE) on behavior cognition and synaptic plasticity balance (SPB), and tried to understand a possible mechanism by evaluating the alternation of SPB. The animal model was produced by ethanol exposure throughout gestational period with 4 g/kg bodyweight. Offspring of both male and female were selected and studied on postnatal days 36. Subsequently, the data showed that chronic ethanol exposure resulted in birth weight reduction, losing bodyweight gain, microcephaly and hippocampus weight retardation. In Morris water maze (MWM) test, escape latencies were significantly higher in CPEE-treated rats than that in control ones. They also spent much less time in the target quadrant compared to that of control animals in the probe phase. In addition, it was found that there was a more severe impairment in females than that in males after CPEE treatment. Electrophysiological studies showed that CPEE considerably inhibited hippocampal LTP and facilitated depotentiation in males, while significantly enhanced LTP and suppressed depotentiation in females. A novel index, developed by us, showed that the action of CPEE on SPB was more sensitive in females than that in males, suggesting that it might be an effective index to distinguish the difference of SPB impairment between males and females. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Modeling accumulations of particles in lung during chronic inhalation exposures that lead to impaired clearance

    SciTech Connect

    Wolff, R.K.; Griffith, W.C. Jr.; Cuddihy, R.G.; Snipes, M.B.; Henderson, R.F.; Mauderly, J.L.; McClellan, R.O. )

    1989-01-01

    Chronic inhalation of insoluble particles of low toxicity that produce substantial lung burdens of particles, or inhalation of particles that are highly toxic to the lung, can impair clearance. This report describes model calculations of accumulations in lung of inhaled low-toxicity diesel exhaust soot and high-toxicity Ga2O3 particles. Lung burdens of diesel soot were measured periodically during a 24-mo exposure to inhaled diesel exhaust at soot concentrations of 0, 0.35, 3.5, and 7 mg m-3, 7 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y after a 4-wk exposure to 23 mg Ga2O3 m-3, 2 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y both studies using inhaled radiolabeled tracer particles. Simulation models fit the observed lung burdens of diesel soot in rats exposed to the 3.5- and 7-mg m-3 concentrations of soot only if it was assumed that clearance remained normal for several months, then virtually stopped. Impaired clearance from high-toxicity particles occurred early after accumulations of a low burden, but that from low-toxicity particles was evident only after months of exposure, when high burdens had accumulated in lung. The impairment in clearances of Ga2O3 particles and radiolabeled tracers was similar, but the impairment in clearance of diesel soot and radiolabeled tracers differed in magnitude. This might have been related to differences in particle size and composition between the tracers and diesel soot. Particle clearance impairment should be considered both in the design of chronic exposures of laboratory animals to inhaled particles and in extrapolating the results to people.

  16. [Effect of copper sulphate on the lung damage induced by chronic intermittent exposure to ozone].

    PubMed

    Oyarzún G, Manuel J; Sánchez R, Susan A; Dussaubat D, Nelson; Miller A, María E; González B, Sergio

    2017-01-01

    Ozone exposure could increase lung damage induced by airborne particulate matter. Particulate matter lung toxicity has been attributed to its metallic content. To evaluate the acute effect of intratracheal administration of copper sulfate (CuSO4) on rat lungs previously damaged by a chronic intermittent ozone exposure. Two-months-old male Sprague-Dawley rats were exposed to 0.5 ppm ozone four h per day, five days a week, during two months. CuSO4 was intratracheally instilled 20 h after ozone exposure. Controls breathed filtered air or were instilled with 0.9% NaCl or with CuSO4 or were only exposed to ozone. We evaluated lung histopathology. F2 isoprostanes were determined in plasma. Cell count, total proteins, γ glutamyl-transpeptidase (GGT) and alkaline phosphatases (AP) were determined in bronchoalveolar lavage fluid (BALF). Ozone increased total cell count, macrophages, proteins and AP in BALF (p < 0.05), and induced pulmonary neutrophil inflammation. CuSO4 plus air increased plasma F2 isoprostane levels and total cell count, neutrophils and proteins in BALF (p < 0.05). Histopathology showed foamy macrophages. Ozone plus CuSO4 exposed animals showed a neutrophil inflammatory lung response and an increase in total cell count, proteins, GGT and AP in BALF (p < 0.05). Foamy and pigmented alveolar macrophages were detected in all lungs of these animals (p < 0.001). Intratracheal instillation of a single dose of CuSO4 in rats previously subjected to a chronic and intermittent exposure to ozone induces a neutrophil pulmonary inflammatory response and cytoplasmic damage in macrophages.

  17. Parasitism in marine fish after chronic exposure to petroleum hydrocarbons in the laboratory and to the Exxon Valdez oil spill

    SciTech Connect

    Khan, R.A. )

    1990-05-01

    Crude oil or its water soluble components are known to induce histopathological effects in fish following chronic exposure. Fish tend to harbor a variety of parasites, most of which under natural conditions cause little or no apparent harm. However, after chronic exposure to petroleum hydrocarbons, the prevalence and intensity of parasitism increases substantially. Trichodinid ciliates are mainly ectoparasitic protozoans on the fills of fish. Since a previous study showed that chronic exposure to crude oil fractions resulted in increased parasitism, a study was initiated to ascertain the relationship between trichodinid infections and exposure of fish to crude oil or its fractions in the laboratory and subsequently, in the Gulf of Alaska following the Exxon Valdez oil spill.

  18. Coding region paraoxonase polymorphisms dictate accentuated neuronal reactions in chronic, sub-threshold pesticide exposure.

    PubMed

    Browne, R Orie; Moyal-Segal, Liat Ben; Zumsteg, Dominik; David, Yaron; Kofman, Ora; Berger, Andrea; Soreq, Hermona; Friedman, Alon

    2006-08-01

    Organophosphate pesticides (OPs), known inhibitors of acetylcholinesterase (AChE), are used extensively throughout the world. Recent studies have focused on the ACHE/PON1 locus as a determinant of inherited susceptibility to environmental OP exposure. To explore the relationship of the corresponding gene-environment interactions with brain activity, we integrated neurophysiologic, neuropsychological, biochemical, and genetic methods. Importantly, we found that subthreshold OP exposure leads to discernible physiological consequences that are significantly influenced by inherited factors. Cortical EEG analyses by LORETA revealed significantly decreased theta activity in the hippocampus, parahippocampal regions, and the cingulate cortex, as well as increased beta activity in the prefrontal cortex of exposed individuals-areas known to play a role in cholinergic-associated cognitive functions. Through neuropsychological testing, we identified an appreciable deficit in the visual recall in exposed individuals. Other neuropsychological tests revealed no significant differences between exposed and non-exposed individuals, attesting to the specificity of our findings. Biochemical analyses of blood samples revealed increases in paraoxonase and arylesterase activities and reduced serum acetylcholinesterase activity in chronically exposed individuals. Notably, specific paraoxonase genotypes were found to be associated with these exposure-related changes in blood enzyme activities and abnormal EEG patterns. Thus, gene-environment interactions involving the ACHE/PON1 locus may be causally involved in determining the physiological response to OP exposure.

  19. Chronic exposure to ozone causes tolerance to airway hyperresponsiveness in guinea pigs: lack of SOD role.

    PubMed

    Vargas, M H; Romero, L; Sommer, B; Zamudio, P; Gustin, P; Montaño, L M

    1998-05-01

    Tolerance to respiratory effects of O3 has been demonstrated for anatomic and functional changes, but information about tolerance to O3-induced airway hyperresponsiveness (AHR) is scarce. In guinea pigs exposed to air or O3 (0.3 parts/million, 4 h/day, for 1, 3, 6, 12, 24, or 48 days, studied 16-18 h later), pulmonary insufflation pressure changes induced by intravenous substance P (SP, 0.032-3.2 micro ug/kg) were measured, then the animals were subjected to bronchoalveolar lavage (BAL). Bronchial rings with or without phosphoramidon were also evaluated 3 h after air or a single O3 exposure. O3 caused in vivo AHR (increased sensitivity) to SP after 1, 3, 6, 12, and 24 days of exposure compared with control. However, after 48 days of exposure, O3 no longer caused AHR. Total cell, macrophage, neutrophil, and eosinophil counts in BAL were increased in most O3-exposed groups. When data from all animals were pooled, we found a highly significant correlation between degree of airway responsiveness and total cells (r = 0.55), macrophages (r = 0.54), neutrophils (r = 0.47), and eosinophils (r = 0.53), suggesting that airway inflammation is involved in development of AHR to SP. Superoxide dismutase (SOD) levels in BAL fluids were increased (P < 0.05) after 1, 3, 6, and 12 days of O3 exposure and returned to basal levels after 24 and 48 days of exposure. O3 failed to induce hyperresponsiveness to SP in bronchial rings, and phosphoramidon increased responses to SP in air- and O3-exposed groups, suggesting that neutral endopeptidase inactivation was not involved in O3-induced AHR to SP in vivo. We conclude that chronic exposure to 0. 3 ppm O3, a concentration found in highly polluted cities, resulted in tolerance to AHR to SP in guinea pigs by an SOD-independent mechanism.

  20. Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

    PubMed

    Ren, Xuefeng; Wu, Xin; Sui, Gang; Gong, Zhihong; Yawson, Emmanuel; Wu, Banghua; Lai, Guanchao; Ruan, Xiaolin; Gao, Hongbin; Zhou, Feng; Su, Bing; Olson, James R; Tang, Xiaojiang

    2015-05-01

    We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.

  1. Chronic intermittent ethanol exposure produces persistent anxiety in adolescent and adult rats.

    PubMed

    Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-02-01

    Ethanol (EtOH) dependence and tolerance in the adult are marked by increased function of NMDA receptors and decreased function of GABAA receptors, which coincide with altered receptor subunit expression in specific brain regions. Adolescents often use EtOH at levels greater than adults, yet the receptor subunit expression profiles following chronic intermittent EtOH (CIE) exposure in adolescents are not known. Persistent age-dependent changes in receptor subunit alterations coupled with withdrawal-related anxiety may help explain the increase in alcohol abuse following adolescent experimentation with the drug. Adolescent and adult rats received 10 intraperitoneal administrations of 4.0 g/kg EtOH or saline every 48 hours. At either 24 hours or 12 days after the final exposure, anxiety-like behavior was assessed on the elevated plus maze and tissue was collected. Western blotting was used to assess changes in selected NMDA and GABAA receptor subunits in whole cortex and bilateral hippocampus. CIE exposure yields a persistent increase in anxiety-like behavior in both age groups. However, selected NMDA and GABAA receptor subunits were not differentially altered by this CIE exposure paradigm in adolescents or adults. CIE exposure produced persistent anxiety-like behavior, which has important implications for alcohol cessation. Given the reported behavioral and neuropeptide expression changes in response to this dose of EtOH, it is important for future work to consider the circumstances under which these measures are altered by EtOH exposure. Copyright © 2015 by the Research Society on Alcoholism.

  2. Chronic trimethyltin chloride exposure and the development of kidney stones in rats

    PubMed Central

    Ren, Xuefeng; Wu, Xin; Sui, Gang; Gong, Zhihong; Yawson, Emmanuel; Wu, Banghua; Lai, Guanchao; Ruan, Xiaolin; Gao, Hongbin; Zhou, Feng; Su, Bing; Olson, James R.; Tang, Xiaojiang

    2015-01-01

    We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague–Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 μg kg−1 day−1. Transient behavioral changes were observed in the high-dose group during the first 2weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H+/K+-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 μg kg−1 day−1 dose group and 3 out of 9 rats in the 131.3 μg kg−1 day−1 dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones. PMID:25224689

  3. Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood

    PubMed Central

    Varlinskaya, Elena I.; Truxell, Eric; Spear, Linda P.

    2014-01-01

    This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25–45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45–65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later in

  4. Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep.

    PubMed

    Kallapur, Suhas G; Kramer, Boris W; Knox, Christine L; Berry, Clare A; Collins, Jennifer J P; Kemp, Matthew W; Nitsos, Ilias; Polglase, Graeme R; Robinson, James; Hillman, Noah H; Newnham, John P; Chougnet, Claire; Jobe, Alan H

    2011-09-01

    The chorioamnionitis associated with preterm delivery is often polymicrobial with ureaplasma being the most common isolate. To evaluate interactions between the different proinflammatory mediators, we hypothesized that ureaplasma exposure would increase fetal responsiveness to LPS. Fetal sheep were given intra-amniotic (IA) injections of media (control) or Ureaplasma parvum serovar 3 either 7 or 70 d before preterm delivery. Another group received an IA injection of Escherichia coli LPS 2 d prior to delivery. To test for interactions, IA U. parvum-exposed animals were challenged with IA LPS and delivered 2 d later. All animals were delivered at 124 ± 1-d gestation (term = 150 d). Compared with the 2-d LPS exposure group, the U. parvum 70 d + LPS group had 1) decreased lung pro- and anti-inflammatory cytokine expression and 2) fewer CD3(+) T lymphocytes, CCL2(+), myeloperoxidase(+), and PU.1(+) cells in the lung. Interestingly, exposure to U. parvum for 7 d did not change responses to a subsequent IA LPS challenge, and exposure to IA U. parvum alone induced mild lung inflammation. Exposure to U. parvum increased pulmonary TGF-β1 expression but did not change mRNA expression of either the receptor TLR4 or some of the downstream mediators in the lung. Monocytes from fetal blood and lung isolated from U. parvum 70 d + LPS but not U. parvum 7 d + LPS animals had decreased in vitro responsiveness to LPS. These results are consistent with the novel finding of downregulation of LPS responses by chronic but not acute fetal exposures to U. parvum. The findings increase our understanding of how chorioamnionitis-exposed preterm infants may respond to lung injury and postnatal nosocomial infections.

  5. Chronic arsenic exposure and risk of infant mortality in two areas of Chile.

    PubMed Central

    Hopenhayn-Rich, C; Browning, S R; Hertz-Picciotto, I; Ferreccio, C; Peralta, C; Gibb, H

    2000-01-01

    Chronic arsenic exposure has been associated with a range of neurologic, vascular, dermatologic, and carcinogenic effects. However, limited research has been directed at the association of arsenic exposure and human reproductive health outcomes. The principal aim of this study was to investigate the trends in infant mortality between two geographic locations in Chile: Antofagasta, which has a well-documented history of arsenic exposure from naturally contaminated water, and Valparaíso, a comparable low-exposure city. The arsenic concentration in Antofagasta's public drinking water supply rose substantially in 1958 with the introduction of a new water source, and remained elevated until 1970. We used a retrospective study design to examine time and location patterns in infant mortality between 1950 and 1996, using univariate statistics, graphical techniques, and Poisson regression analysis. Results of the study document the general declines in late fetal and infant mortality over the study period in both locations. The data also indicate an elevation of the late fetal, neonatal, and postneonatal mortality rates for Antofagasta, relative to Valparaíso, for specific time periods, which generally coincide with the period of highest arsenic concentration in the drinking water of Antofagasta. Poisson regression analysis yielded an elevated and significant association between arsenic exposure and late fetal mortality [rate ratio (RR) = 1.7; 95% confidence interval (CI), 1.5-1.9], neonatal mortality (RR = 1.53; CI, 1.4-1.7), and postneonatal mortality (RR = 1.26; CI, 1.2-1.3) after adjustment for location and calendar time. The findings from this investigation may support a role for arsenic exposure in increasing the risk of late fetal and infant mortality. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:10903622

  6. Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood.

    PubMed

    Varlinskaya, Elena I; Truxell, Eric; Spear, Linda P

    2014-08-01

    This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later

  7. Exposure to outdoor air pollution and chronic bronchitis in adults: a case-control study.

    PubMed

    Salameh, P; Salame, J; Khayat, G; Akhdar, A; Ziadeh, C; Azizi, S; Khoury, F; Akiki, Z; Nasser, Z; Abou Abbass, L; Saadeh, D; Waked, M

    2012-10-01

    Although Lebanon is a highly polluted country, so far no study has specifically been designed to assess the association between outdoor air pollution and chronic bronchitis in this country. To assess the association between exposure to outdoor air pollution and chronic bronchitis in Lebanon. A pilot case-control study was conducted in two tertiary care hospitals. Cases consisted of patients diagnosed with chronic bronchitis by a pulmonologist and those epidemiologically confirmed. Controls included individuals free of any respiratory signs or symptoms. After obtaining informed consent, a standardized questionnaire was administered. Bivariate, stratified (over smoking status and gender) and multivariate analyses revealed that passive smoking at home (ORa: 2.56, 95% CI: 1.73-3.80) and at work (ORa: 1.89, 95% CI: 1.13-3.17); older age (ORa: 1.75, 95% CI: 1.55-2.39); lower education (ORa: 1.44, 95% CI: 1.21-1.72); living close to a busy road (ORa: 1.95, 95% CI: 1.31-2.89) and to a local power plant (ORa: 1.62, 95% CI: 1.07-2.45); and heating home by hot air conditioning (ORa: 1.85, 95% CI: 1.00-3.43) were moderately associated with chronic bronchitis; an inverse association was found with heating home electrically (ORa: 0.58, 95% CI: 0.39-0.85). A positive dose-effect relationship was observed in those living close to a busy road and to a local diesel exhaust source. Chronic bronchitis is associated with outdoor air pollution.

  8. Gold granuloma after accidental implantation.

    PubMed Central

    Scott, F R; Dhillon, A P; Lewin, J F; Flavell, W; Laws, I M

    1995-01-01

    A case, in a 66 year old man, of a florid granulomatous reaction to gold dental alloy presenting about 20 years after accidental implantation in the oral mucosa of the lip is reported. Subsequent energy dispersive analysis confirmed the presence of a high nobility gold dental alloy. Florid granulomatosis has only rarely been reported in association with gold. Possible explanations for the delay in presentation include alteration of immune status or the development of hypersensitivity with components of the gold dental alloy acting as haptens. Images PMID:8543638

  9. Accidental poisoning with autumn crocus.

    PubMed

    Gabrscek, Lucija; Lesnicar, Gorazd; Krivec, Bojan; Voga, Gorazd; Sibanc, Branko; Blatnik, Janja; Jagodic, Boris

    2004-01-01

    We describe a case of a 43-yr-old female with severe multiorgan injury after accidental poisoning with Colchicum autumnale, which was mistaken for wild garlic (Allium ursinum). Both plants grow on damp meadows and can be confused in the spring when both plants have leaves but no blossoms. The autumn crocus contains colchicine, which inhibits cellular division. Treatment consisted of supportive care, antibiotic therapy, and granulocyte-directed growth factor. The patient was discharged from the hospital after three weeks. Three years after recovery from the acute poisoning, the patient continued to complain of muscle weakness and intermittent episodes of hair loss.

  10. Persistence of DNA damage following exposure of human bladder cells to chronic