Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to characterize the effects of diesel exhaust particles (DEP) on thiol regulation in alveolar macrophages (AM) and lymphocytes. We obtained AM and lymph node (thymic and tracheal) cells (LNC) (at different time points) from rats exposed intratracheally to DEP (5 mg/kg) or saline, and measured inflammatory markers, thiol levels, and glutathione reductase (GSH-R) activity. DEP exposure produced significant increases in neutrophils, lactate dehydrogenase, total protein, and albumin content in the lavage fluid. AM from DEP-exposed rats showed a time-dependent increase in intracellular cysteine (CYSH) and GSH. In LNC the intracellular GSH reached peak level by 24 hr, declining toward control levels by 72 hr after exposure. LNC-CYSH and AM-CYSH and GSH were increased at both 24 and 72 hr. Both Sprague-Dawley and Brown Norway rats showed similar trends of responses to DEP exposure as per measurement of the inflammatory markers and thiol changes. AM and, to a lesser degree, LNC were both active in cystine uptake. The DEP exposure stimulated GSH-R activity and increased the conversion of cystine to CYSH in both cell types. The intracellular level of GSH in DEP-exposed AM was moderately increased compared with the saline control, and was further augmented when cells were incubated with cystine. In contrast, the intracellular level of GSH in DEP-exposed LNC was significantly reduced despite the increased CYSH level and GSH-R activity when these cells were cultured for 16 hr. DEP absorbed 23-31% of CYSH, cystine, and GSH, and only 8% of glutathione disulfide when incubated in cell free media. These results indicate that DEP exposure caused lung inflammation and affected thiol levels in both AM and LNC.
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PMID:Alteration of intracellular cysteine and glutathione levels in alveolar macrophages and lymphocytes by diesel exhaust particle exposure. 1194 Apr 52

Brown Norway rats were exposed by intratracheal instillation of saline, carbon black (CB), or diesel exhaust particles (DEP) (5 mg/kg) on day 1, followed by exposure to ovalbumin (OVA, 90 mg/m(3)) or saline for 30 minutes on days 1, 8, 15, and 29. Animals were sacrificed on day 30. The DEP, CB, or OVA exposure alone did not result in abnormal levels of inflammatory cells, lactate dehydrogenase (LDH), or total protein in the lavage fluid. In combined OVA-DEP or OVA-CB exposure, however, these markers were significantly increased. The adjuvant effect of CB and DEP on OVA sensitization was evidenced by the marked increases in serum OVA-specific IgG (5.6-fold) and IgE (3.5-4 fold) levels, and the increase in interleukin-4 (IL-4) mRNA levels in lung tissue. The OVA exposure markedly reduced glutathione (GSH) levels in both cell types. In combined DEP-OVA exposure, the level of GSH in lymphocytes was further decreased, indicating a possible interactive effect between DEP and OVA exposures. These results show that both DEP and CB augmented OVA-induced allergic sensitization, and that particle composition of DEP may not be a critical factor for the adjuvant effect. OVA exposure causes significant depletion of intracellular GSH in lymphocytes, which may play a key role in OVA-mediated immune responses.
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PMID:The effect of diesel exhaust particles (DEP) and carbon black (CB) on thiol changes in pulmonary ovalbumin allergic sensitized Brown Norway rats. 1209 28

The purpose of the present study was to examine the effects of aging, inactivity and weight-bearing exercise on fast-twitch single Type IIB skeletal muscle fibers from the superficial region of the lateral head of the gastrocnemius (Type IIB fibers). Specifically, this study compared the biochemical properties of Type IIB fibers after 7 days of hindlimb unweighting (HU), 7 days of HU with intermittent weight-bearing (HU-Ex), and cage control (C) from adult and aged Fischer 344 Brown Norway F1 Hybrid rats (12- and 30-month old). Biochemical measurements included total lactate dehydrogenase (LDH) and beta-hydroxy-acyl-coenzyme A dehydrogenase activities (BHAD), expressed in nmoles/microg/hr dry weight. Fiber-typing for myosin heavy chain isoform was determined by SDS-PAGE. With age, LDH activity in Type IIB fibers decreased from 52.0 +/- 3.4 nmoles/microg/hr (12-month old) to 39.5 +/- 2.9 nmoles/microg/hr (30-month old). Following HU, LDH activity of single Type IIB fibers increased by 22% (52.0 +/- 3.4 to 66.4 +/- 3.2 nmoles/microg/hr) in the 12-month-old animals, whereas no difference was observed with HU in the Type IIB fibers of the 30-month-old animals. Following HU-Ex, LDH activity of Type IIB fibers in the 12-month-old animals was not significantly different from that of Type IIB fibers from HU animals, whereas a significant increase was observed (38.1 +/- 2.9 to 51.8 +/- 3.1 nmoles/microg/hr) in Type IIB fibers of 30-month-old animals, for HU and HU-Ex, respectively. Analysis of variance revealed an interaction between age and condition, indicating that Type IIB fibers from adult and aged animals have a different biochemical response to inactivity. The enzyme activities for BHAD were not different between the experimental conditions. The results demonstrate that the total LDH enzyme activities of the Type IIB fibers decrease with age, suggesting an age-related shift in the biochemical profile. Further, single skeletal muscle fiber adaptation is age-dependent.
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PMID:Enzymatic alterations in single type IIB skeletal muscle fibers with inactivity and exercise in 12- and 30-month-old rats. 1260 68

The incidence of allergies and asthma has increased significantly in the past few decades. The objectives of this study were to establish an allergy model in weanling rats to more closely reflect the developing immune system of children, and to determine whether systemic administration of inactivated Bordetella pertussis could enhance pulmonary and systemic immune responses to locally administered house dust mite antigen (HDM). Three-week old female Brown Norway rats were sensitized with 10 micro g HDM intratracheally or intraperitoneally, with or without a simultaneous injection of 10(8) whole killed B. pertussis organisms. Ten days later, all the rats were challenged with 5 micro g HDM via the trachea. Bronchial lymph nodes and bronchoalveolar lavage fluid (BAL) were collected 0, 2, and 4 days post-challenge. Coadministration of pertussis and intratracheal instillation of HDM enhanced HDM-specific lymphoproliferative responses and increased BAL levels of total protein, lactate dehydrogenase, HDM-specific IgE and IgG antibodies, and the number of eosinophils in BAL to the same extent as had occurred in the systemically immunized animals. The data show that intratracheal instillation of HDM induces a mild allergic sensitization in juvenile rats, and that ip injection with B. pertussis enhances this sensitization process to levels seen in animals injected with antigen and B pertussis together. These results suggest that simultaneous exposure to Th2-inducing vaccine components and allergenic proteins may be a risk factor for allergic sensitization and the development of asthma in susceptible individuals.
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PMID:Systemic administration of Bordetella pertussis enhances pulmonary sensitization to house dust mite in juvenile rats. 1260 40

This study was conducted to determine the effects of Korean soybean paste (doen-jang [dwen-jahng]) (at concentrations of 0.5, 1, and 5%) on the toxicity of 500 ppb of aflatoxin in the diets of 60 laying hens (Isa Brown) divided into five groups and treated from week 15 to week 67. The aflatoxin-treated hens exhibited many deleterious effects, including reduced body weight; increased relative organ weights; decreased egg production; aflatoxin accumulation in eggs; decreased serum calcium, phosphorus, and alanino amonotransferase (ALT) levels; increased serum gammaglutamil transferase and lactic dehydrogenase levels; and, most significantly, severely altered cell foci and sinusoid dilatation in the liver, relative to control hens. The feeding of 1% soybean paste to hens reduced the adverse effects of aflatoxin on body weight, relative organ weights, egg production, and aflatoxin accumulation in eggs and improved serum calcium and ALT levels and the histopathological lesions of the liver. The feeding of 5% soybean paste to hens resulted in higher levels of the same types of improvements, especially with regard to the histopathological findings for the liver. On the basis of these results, it was suggested that a diet including 5% (and in some cases only 1%) Korean soybean paste protected laying hens and their eggs from the major deleterious effects of 500 microg of aflatoxin per kg of diet and from aflatoxin accumulation. These results indicate that dietary supplementation with Korean soybean paste reduces aflatoxin toxicity in laying hens that ultimately produce human foods such as eggs and poultry.
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PMID:Reduction of aflatoxins by Korean soybean paste and its effect on cytotoxicity and reproductive toxicity--Part 3. Inhibitory effects of Korean soybean paste (doen-jang) on aflatoxin toxicity in laying hens and aflatoxin accumulation in their eggs. 1274 98

Influenza is a respiratory tract disease of viral origin that can cause major epidemics in humans. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembles those seen in humans with influenza, and can result in severe and even fatal pneumonia. In contrast, experimental infection of rats with the virus induces a milder form of the disease, with no mortality. The purpose of the study reported here was to determine the time course of influenza infection and lung injury in Brown Norway (BN), Fischer-344 (F344), and Sprague-Dawley (SD) rats to ascertain whether genetic background impacts susceptibility to infection and host responses. Rats of each strain were inoculated intranasally with 10,000 plaque-forming units of rat-adapted influenza virus (RAIV), and lungs were assessed at postinoculation hour (PIH) 2, 24, 48, 72, and 144 for viral titer, inflammatory cells, pro-inflammatory cytokines, and biochemical indicators of lung edema (protein) and injury (lactate dehydrogenase [LD] activity). Virus titer peaked at PIH 24, and was 100-fold higher in the F344 and SD, compared with the BN strain. Alveolar macrophages, LD activity, and total protein concentration were higher in the BN rats, whereas neutrophil numbers and interleukin 6 and tumor necrosis factor-alpha activities were greatest in the bronchoalveolar lavage fluid of F344 and SD rats. The results indicate that F344 and SD rats respond in similar manner to viral infection, whereas viral replication was more limited in BN rats and was associated with a different profile of pulmonary cells.
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PMID:Kinetic profile of influenza virus infection in three rat strains. 1286 75

Dose-dependent specific antibody production, antigen-dependent pulmonary inflammation, and thiol changes in the lung and associated lymph nodes were examined in a Brown Norway rat model of pulmonary sensitization. Cysteine (CYSH), glutathione (GSH), and markers of inflammation in bronchoalveolar lavage fluid (BALF) were measured following ovalbumin (OVA) inhalation challenge. Alveolar macrophages (AM) and pulmonary-associated lymph node cells (LNC) were isolated and intracellular CYSH and GSH assessed. OVA-specific IgE and IgG antibodies were quantified from sera. A dose-dependent biphasic response was noted with respect to OVA-specific IgE. OVA-specific IgG concentrations were maximal at 68 mg (OVA)/m3. OVA challenge to sensitized rats induced increases in BALF albumin, total protein, lactate dehydrogenase, CYSH and GSH that were independent of serum antibody concentrations. AM thiols were modestly elevated at low OVA challenge doses, but sharply reduced at the higher OVA challenge doses. In contrast, both thiols were dose dependently elevated in BALE CYSH, but not GSH, was elevated in LNC of OVA challenged rats. In summary, antigen exposure caused a dose-dependent alteration of inflammatory, thiol and immune parameters in OVA sensitized and challenged rats. Changes in thiol levels did not correlate with antibody responses. While the results of the present study do not support a functional role for thiols in the immune response, it is important to note the dose-dependent dramatic alteration seen in thiols following sensitization and challenge.
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PMID:Dose-dependent thiol and immune responses to ovalbumin challenge in Brown Norway rats. 1506 34

Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.
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PMID:Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation. 1612 Jul 49

Allergic asthma is a complex chronic inflammatory disease of the airways and its etiology is multifactorial. It involves the recruitment and activation of many inflammatory and structural cells, all of which release inflammatory mediators that result in typical pathological changes of asthma. The features of asthma addressed in this Brown Norway (BN) rat animal model include an analysis of cellular infiltrations in the lung, inflammatory factors in bronchoalveolar lavage (BAL), total immunoglobulin E (IgE) production in serum, and changes in delayed-onset respiratory reactions upon four inhalation challenges (every 2 wk) with polymeric diphenylmethane diisocyanate (MDI) aerosol in two groups of topically sensitized rats. The dependence on the induction-related variables was analyzed by using almost identical surface area doses but different total doses per animal. This regimen caused acute exacerbations of delayed-onset respiratory reactions, for which intensity increased with each challenge. After the fourth challenge BAL neutrophils, lymphocytes, eosinophils, cell counts, protein, and lactate dehydrogenase (LDH) as well as lung weights were significantly increased in sensitized rats relative to naive but challenged controls. Histopathology revealed activated bronchial lymphatic tissue, increased recruitment of inflammatory cells, the beginning of peribronchial/peribronchiolar fibrosis, thickening of alveolar septae, and vascular hypertrophy. Total IgE in serum was significantly increased in sensitized rats. Thus, high-dose topical induction to, and repeated inhalation challenges with, MDI was associated with a marked neutrophilic and a less consistent eosinophilic inflammatory response. With regard to the relative sensitivity of endpoints, those that integrate independently a series of complex physiological events appeared to be most practical to probe positive responses in this animal model. These include postchallenge changes in Penh to identify respiratory responses delayed in onset as well as inflammatory changes in BAL. In summary, this extension of a previous study that used 16 mg MDI/m(3) instead of 39 mg MDI/m(3) that was used in the current study for challenge exposures demonstrates that protocol variables are most critical for the outcome of test. Moreover, the sensitivity of this bioassay to define the typical asthma phenotype can be markedly improved by measurements of respiratory responses delayed in onset rather than immediate in onset. Accordingly, to increase the efficacy of this asthma model moderately irritant concentrations of the hapten have to be used for challenge and at least three to four adequately spaced challenge exposures are required to elicit a typical asthma phenotype.
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PMID:Brown Norway rat asthma model of diphenylmethane 4,4'-diisocyanate. 1619 8

Metabolic alterations have been characterized in various heart diseases. However, no data are available concerning metabolic changes during acute rejection episodes. Heterotopic heart transplantations in rats were done using Lewis rats as donors and recipients as a control group. The rejection group included Brown-Norway rat donors to Lewis rat recipients. Nonoperated hearts were also studied. Enzyme activities were determined for phosphofructokinase, pyruvate kinase, and lactate dehydrogenase. There were no alterations in the control group compared to nonoperated hearts. However, the rejection cohort of hearts showed decreased glycolytic enzymes. Although lactate dehydrogenase maintained similar levels compared to the control group, phosphofructokinase showed only 50% activity, and pyruvate kinase showed less than 10% of the activity compared with controls. These results suggested that metabolic alterations in rejected hearts differ from other cardiomyopathies.
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PMID:Glycolytic enzyme activities are decreased during acute rejection in transplanted rat hearts. 1638 41


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