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Biomedical subjects

A Fairbrother

Publications and source records attributed to A Fairbrother.

At least 19 recordsLinked to original sources

Effects of Aroclor 1254 on the thyroid gland, immune function, and hepatic cytochrome P450 activity in mallards.

Adult male mallards were exposed to 0, 4, 20, 100, 250, and 500 mg/kg Aroclor 1254 by gavage twice per week for 5 weeks. Immunotoxic effects, as measured by antibody titers to sheep erythrocytes, natural killer cell activity and lymphocyte mitogenesis to phytohemagglutinin, were not detected as a consequence of polychlorinated biphenyl (PCB) exposure. Hepatic cytochrome P450 activities were measured as microsomal dealkylations of ethoxyresorufin (EROD) and pentoxyresorufin (PROD). Significant elevations in EROD and PROD were noted at 20 mg/kg and peaked in birds treated with 100 mg/kg. Total P450 was induced beginning at 100 mg/kg and peaked at 250 mg/kg. Relative liver weights were dose-dependently increased following treatment with 100 mg/kg or more. Thyroid weights were significantly increased in PCB-treated birds treated with 100 mg/kg or greater, but no significant histological abnormalities were observed, except at the highest dose. Plasma total triiodothyronine (T3) was decreased in a dose-dependent manner, with a significant lowest-observed-adverse-effect level (LOAEL) of 20 mg/kg. T3 was decreased following 7 days treatment with 100 mg/kg. The no-observed-adverse-effect level (NOAEL) was 4 mg/kg for decreased T3. Plasma glucose levels were decreased on days 28 and 35 in mallards treated with 500 mg/kg, while other clinical plasma biochemistry parameters were unaltered by PCB treatment. Plasma corticosterone levels were unchanged by PCB treatment. These results indicate that thyroid hormone levels and P450 activity in mallards are sensitive to subchronic PCB exposure in the absence of gross toxic effects and immunotoxicity.

Animals

Effects of induced hypo- and hyperthyroidism on immune function and plasma biochemistry in mallards (Anas platyrhynchos).

Hypo- or hyperthyroid states were induced in adult male mallards (Anas platyrhynchos) by subchronic exposure to daily injections of methimazole or a 9:1 ratio of thyroxine (T4): triiodothyronine (T3). The levels of T4 given were 0, 125, 250, or 500 micrograms/kg/day and for methimazole; 10 mg/kg/day for 22 or 21 days. Plasma T3 showed a lasting decrease with T4:T3 treatment, despite the attempt to maintain the normal T4:T3 ratio. Antibody formation to sheep red blood cells was decreased only at the 125 micrograms/kg/day dose of T4, and was unaffected by methimazole treatment. Natural killer cell activity to RP-9 tumor cells and macrophage phagocytosis of killed, opsonized Saccaromyces cereviseae were unaffected by treatment throughout the study. However, lectin-dependent cellular cytotoxic activity to RP-9 tumor cells was significantly decreased after 21 days of methimazole treatment, indicating that hypothyroidism may have an influence on cell-mediated immunity. Hypo- and hyperthyroid conditions had opposing effects on plasma cholesterol levels.

Animals

Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether (DE-71) in C57BL/6J mice.

Polybrominated diphenyl ethers are manufactured for use as flame retardants in commercial plastics and textiles in Europe and North America. These studies investigated the acute and subchronic immunotoxicity and endocrine effects of a commercial pentabromodiphenyl either mixture, DE-71, in female C57BL/6 mice. Mice were orally exposed to acute single doses of DE-71 of 0, 0.8, 4.0, 20, 100, or 500 mg/kg, or to subchronic daily doses totaling 0, 250, 500, or 1000 mg/kg over a 14 day period. Immunotoxicity was assessed by measuring the plaque-forming cell response to sheep erythrocytes (SRBC) and natural killer cell (NKC) activity (basal and poly I:C stimulated) to YAC-1 target cells. Liver cytochrome P450 content and activities (ethoxyresorufin-o-deethylase (EROD) and pentoxyresorufin-o-deethylase (PROD)) as well as corticosterone (CS) and thyroxine (T4) concentrations were also measured. PROD activity was induced 3-5-fold in mice exposed acutely or subchronically to DE-71 at doses > 250 mg/kg. EROD activity and total microsomal cytochrome P450 content were significantly induced only in mice treated subchronically with DE-71; maximum induction of EROD was 3.3-fold. Total serum T4 concentrations were significantly lower in mice treated acutely with DE-71 at all doses except the 100 mg/kg dose. Total and free T4 concentrations were dose-dependently decreased in DE-71-treated mice following subchronic exposure. Plasma CS levels were elevated following subchronic exposure to DE-71. The elevation of CS was correlated with order of capture at necropsy, suggesting an interactive effect of DE-71 and stress. In regard to immunotoxicity, significant suppression of the anti-SRBC response was seen only in mice exposed subchronically to 1000 mg DE-71/kg, an exposure that also resulted in decreased thymus weight. NKC activity was not altered by exposure to DE-71.

Animals

Impairment of growth and immune function of avocet chicks from sites with elevated selenium, arsenic, and boron.

Avocets (Recurvirostra americana) hatched from eggs collected from the south Central Valley of California (USA) were studied to determine the impact of elevated concentrations of selenium, arsenic, and boron on the immune system and growth to maturity. Corcoran ponds were the reference site with low selenium (1.2 ppb) and arsenic (29 ppb) (boron not measured). Westfarmers Pond had elevated concentrations of selenium (319 ppb), arsenic (127 ppb), and boron (109 ppm). Pryse ponds also had elevated selenium, arsenic, and boron concentrations (13.9 ppb, 1,100 ppb, and 29.4 ppm, respectively). Size at hatch was significantly reduced (P < or = 0.05) in birds from Westfarmers and Pryse ponds. The growth rate was faster, but mean adult size was reduced in birds from Pryse ponds. Avocet chicks from Pryse and Westfarmers ponds exposed solely through in ovo transfer of these elements had significantly increased heterophil:lymphocyte ratios. The phagocytic activity of macrophages also was significantly reduced in these birds, and Pryse Pond birds had an increased proliferative ability of lymphocytes in the presence of concanavalin A, a T-cell mitogen. Avocet chicks (< or = 5 wk old) were captured from the various ponds and the same morphometric and immune function measurements made. The birds that were most severely impacted by exposure to these compounds were those that were collected from Pryse ponds.

Animals

Cyclophosphamide effects on immune function of European starlings.

We developed and tested a battery of immune function assays on adult European starlings (Sturnus vulgaris) exposed to the immunotoxicant cyclophosphamide (CY). Starlings were injected intraperitoneally for three consecutive days with saline or 20 mg/kg CY. Cyclophosphamide did not affect body mass or packed cell volume. However, spleen to body mass ratios and the number of viable spleen cells were lower in CY-treated birds when compared to controls. Peripheral white blood cell numbers were reduced in CY-treated starlings, and the decrease affected all cell types. Phagocytic ability of macrophages cultured from peripheral blood monocytes was impaired in cells from CY-treated birds. Additionally, CY treatment resulted in decreased lymphocyte blastogenesis to the T-cell mitogen Concanavalin A. The hemagglutination response to sheep erythrocytes was lower in birds that had received CY. Thus, these immunological methods detected chemically-induced immune dysfunction in starlings.

Animals

The effect of 2,4-dinitrophenol on the metabolic rate of bobwhite quail.

Bobwhite quail were exposed to 2,4-dinitrophenol (DNP) in a respirometer designed to continuously monitor exchange of O2 and CO2, from which metabolic rates (MR) were estimated. After 14-16 days of acclimation to the system (temperature 22 degrees C, light cycle 8L:14D), hens received feed amended with 0, 625, or 1250 ppm DNP ad libitum for 8 days, followed by 2-5 days of feed containing no DNP. The 625 ppm treatment produced dark-period MR 31-41% higher than corresponding control values, and light-period MR 23-32% higher than controls. The 1250 ppm treatment produced dark-period MR 48-77% higher than control values, and light-period MR 41-67% higher than controls. Over the 8 days of testing, the 625 ppm treatment hens expended 32% more energy than the control hens. Hens consuming 1250 ppm feed expended 60% more energy than control hens and lost most of their body fat. In general, the risk of being unable to meet energy demands for survival or reproduction would probably be substantially increased by the observed elevation in MR.

2,4-Dinitrophenol

An investigation of the effects of carbon loading and endcapping on the solid-phase extraction of beta-blockers onto C18 bonded silica gel.

The effects of carbon loading and endcapping on the solid-phase extraction onto C18 bonded silica gel of a range of beta-blockers from aqueous buffer and from dog plasma has been investigated. The highest extraction efficiencies were obtained for those phases with carbon loadings of between 5 and 16% for phases without endcapping or 10.5-14% for endcapped material. With carbon loadings of 18 and 22% (plus endcapping) poor extractions from the matrix were obtained combined with further losses at the wash steps. Matrix effects were observed with dog plasma which accentuated the effects seen with buffer. These results are best explained by assuming that a cationic interaction of the secondary amino group present in the analytes with residual silanols on the silica surface is primarily responsible for the extraction of these analytes.

Adrenergic beta-Antagonists

Identification of 17-hydroxyprogesterone and other steroid hormones in saliva from a normal child and patients with congenital adrenal hyperplasia by plasmaspray liquid chromatography/mass spectrometry.

A very sensitive, selective and simultaneous method for the analysis of salivary steroid hormones was examined by discharge-assisted thermospray liquid chromatography mass spectrometry (plasmaspray LC/MS). Plasmaspray LC/MS gave [M + H]+ or [MH - H2O]+ as a predominant ion in most of the steroids in this work and in some cases fragment ions were also observed. Eight salivary steroid hormones, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, aldosterone, and testosterone were identified within 10 minutes using the selected ion monitoring technique in conjunction with plasmaspray LC/MS. Progesterone, 17-hydroxyprogesterone, cortisol, aldosterone and testosterone were detected in 1 mL of saliva from a normal child and two patients with congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone

Changes in mallard (Anas platyrhynchos) serum chemistry due to age, sex, and reproductive condition.

Selected serum constituents were analyzed from 50 adult mallards (Anas platyrhynchos) of both sexes during several stages of reproduction: pre-egg laying, egg laying, incubating, molting, and postreproductive. Similar assays were conducted on sera from ducklings aged 5 to 58 days. Values for total protein (TPR), albumin (ALB), glucose (GLU), gamma-glutamyl transferase (GGT), calcium (CA), phosphorus (PHOS) and magnesium (MG) differed by sex. When all data were combined and analyzed for sex-related differences within each reproductive condition separately, all assays except lactate dehydrogenase (LD-L), cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRN) and direct bilirubin (BIDI) differed between sexes during one or more reproductive periods. Each assay showed differences among the various reproductive conditions regardless of gender. The pattern of change differed between sexes. All assays except ALB, GLU, CA and MG showed age-related changes. Lipemia in the sample interfered with all chemistries except TPR, LD-L and CA. Results indicate that when using clinical chemistry as a diagnostic tool in the mallard, age and reproductive condition should be determined in order to compare the data to appropriate control values.

Age Factors

Differential white blood cell values of the mallard (Anas platyrhynchos) across different ages and reproductive states.

Differential white blood cell counts were recorded for adult mallards (Anas platyrhynchos) of both sexes during several stages of reproduction: pre-egg laying, egg laying, incubating, molting, and postreproductive. Similar counts were made for young birds from 5 to 60 days of age. No significant (P less than or equal to 0.05) differences amongst the cell ratios due to sex or reproductive state of the adult birds were noted. Nonlaying and laying birds had similar numbers of thrombocytes which were significantly greater than thrombocyte numbers of incubating, molting or postreproductive birds. Young birds had a decrease in the percent lymphocytes from 50 to greater than 60 days of age and a concomitant, compensating increase in percent heterophils. Thrombocyte numbers increased from 5 days of age to a peak at 18 days of age, after which they did not vary significantly.

Age Factors

Influence of menstrual cycle on serum cholinesterase.

This study examined whether the variability in cholinesterase (ChE) values among and within women may be attributed to phase of menstrual cycle and/or circulating progesterone concentration. Blood was drawn from 21 female subjects once a week for 8 weeks and analyzed for ChE activity and for progesterone concentration. Women ranged in age from 25 to 55 years and five used exogenous hormones (oral contraceptives, estrogen supplements, or progesterone therapy); one woman became pregnant during the study. There was a significant positive correlation between serum ChE and progesterone values only for the two women on oral contraceptives although there were large weekly variations within individuals (CV: 4-32%). Age significantly affected ChE values with 36-40 year olds having the lowest values and 30-35 year olds the highest. This variation in serum ChE probably is due to the influence of some sex steroid but, in women, there is not a direct one-to-one relationship between the enzyme and progesterone. However, when interpreting ChE tests used to monitor exposure of women to pesticides age and hormone intake must be considered in order to avoid false positive results.

Adult

Experimental infection and horizontal transmission of Modoc virus in deer mice (Peromyscus maniculatus).

Deer mice (Peromyscus maniculatus) were inoculated with a sublethal dose of a field strain of Modoc virus to determine patterns of viral persistence, shedding, and transmission. Blood, serum, urine, fecal, and oral swab samples were collected at selected intervals until 63 days postinoculation (PI) after which lung, liver, spleen, kidney, and salivary glands were explanted. Viral assays were conducted by intracranial inoculations of suckling mice and antibody titers were determined by the micro-complement-fixation test. Viremias lasted for up to 4 days PI. Antibody titers were present by day 8 PI, peaked at day 13-20 PI, and persisted until day 63 PI. There was no evidence of viral shedding in urine, fecal, or oral swab samples. Virus was detected in explanted lungs only. In a separate experiment, deer mice were inoculated with virus and lungs were removed from five mice per wk for 10 wk. Indirect fluorescent antibody (IFA) techniques were used to determine the location of virus in lung tissue and to examine fixed tissue for lesions. IFA showed virus in lung parenchymal cells beginning 42 days PI and persisting at least 70 days PI. No histopathologic changes were seen. Horizontal transmission of the virus was studied by placing uninoculated mice with inoculated mice for 42 days and determining if the test animals developed antibodies or had virus in their lungs. Fifty-percent of the uninoculated mice developed antibody. One of these animals had virus in its lungs. Therefore, Modoc virus may be transmitted by direct contact.

Animals

Toxicant-disease-environment interactions associated with suppression of immune system, growth, and reproduction.

The effects of marginal malnourishment , infections, and environmental chemicals on growth and reproductive success in Swiss-Webster white mice and wild deer mice were studied with fractional factorial designs. Interaction effects were discovered. For example, malnourished mice were more sensitive to virus exposure and environmental chemicals (a plant growth regulator or polychlorinated biphenyls). Since several commercial plant growth regulators also appear to suppress the immune system, these results cast doubt on the adequacy of current toxicity testing procedures in which factors are studied individually and not in combination.

Animals