Biomedical subjects

K W Beers

Publications and source records attributed to K W Beers.

13 recordsLinked to original sources

PubMed1992

Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats.

Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2-FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent.

Acute Disease↗

PubMed1992

Renal effects of N-(3,5-disubstitutedphenyl)-succinimides in the Fischer 344 rat.

Previous studies have demonstrated the importance of substitution at the 3- and 5-positions of the phenyl ring in N-phenylsuccinimides for the production of nephrotoxicants in this series of compounds. The purpose of this study was to determine if the electronic nature of the 3,5-substituents is an important determinant for nephrotoxic potential. Male Fischer 344 rats (four rats per group) were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol kg-1) or vehicle, and the renal function was monitored for 48 h. Only N-(3,5-dichlorophenyl)succinimide (0.4 or 1.0 mmol kg-1) induced marked changes in renal function. Urine volume, BUN concentration and proteinuria were increased following N-(3,5-dinitrophenyl)succinimide (1.0 mmol kg-1) treatment but other renal parameters and renal morphology were unchanged in this treatment group. These results indicate that the presence of halogen atoms at the 3- and 5-positions of the phenyl ring in N-phenylsuccinimides is more important for nephrotoxic potential than the presence of non-halogen substituents. The reason why halogen substitution is an important determinant for N-phenylsuccinimide nephrotoxicity is unknown.

Animals↗

PubMed1992

Role of para-hydroxylation in phensuximide-induced urotoxicity in the Fischer 344 rat.

Phensuximide (PSX) is an antiepileptic agent which has been shown to induce hemorrhagic cystitis and mild nephrotoxicity following repeated administration in man or rats or when acutely administered to phenobarbital-pretreated rats. The purpose of this study was to explore the role of para-hydroxylation of the phenyl group of PSX in PSX-induced urotoxicity. Two PSX derivatives, 2-(4-fluorophenyl)-N-methylsuccinimide (FMPS) and N-methyl-2-(4-methylphenyl)succinimide (MMPS), were synthesized and evaluated for urotoxic potential. Male Fischer 344 rats (four rats/group) were administered intraperitoneally (i.p.) a succinimide (0.4 or 1.0 mmol/kg) or vehicle and renal function monitored for 48 h. In a separate experiment, rats were pretreated with phenobarbital (75 mg/kg/day; 3 days, i.p.) prior to succinimide or succinimide vehicle. In non-phenobarbital pretreated rats, acute FMPS or MMPS treatment had little effect on renal function or morphology at the doses tested. Hematuria (+) was noted in the FMPS (1.0 mmol/kg) group on post-treatment day 2. However, in the phenobarbital-pretreated rats, FMPS (0.4 or 1.0 mmol/kg) induced marked hematuria (++) and increased proteinuria while having little or no effect on other renal functional parameters or renal morphology. At killing, bladders of treated rats were distended with bloody urine and exhibited hemorrhagic areas within the bladder wall. In phenobarbital-pretreated rats, MMPS administration had little effect on any renal functional parameter measured or urological morphology. These results suggest that para-hydroxylation does not contribute to the hemorrhagic cystitis induced by PSX.

Animals↗

PubMed1992

Aflatoxin and glutathione in domestic fowl (Gallus domesticus)--II. Effects on hepatic blood flow.

1. The effect of aflatoxin on plasma aspartate aminotransferase (AST), protein, and hepatic glutathione (GSH) and hepatic blood flow (perfusion), were determined in 3-week-old male chickens. 2. Daily aflatoxin gavage (2 mg/kg body wt, in corn oil) for 5 and 10 days elevated plasma AST and hepatic GSH, and depressed plasma protein and hepatic perfusion. Also, renal GSH was elevated after 10 days of aflatoxin treatment. 3. Birds given aflatoxin for 10 days followed by a 10-day recovery period exhibited tissue GSH, plasma AST and protein levels that were not different from control, but hepatic perfusion remained depressed.

Aflatoxins↗

PubMed1992

Aflatoxin and glutathione in domestic fowl (Gallus domesticus)--I. Glutathione elevation and attenuation by high dietary methionine.

1. Changes in hepatic and renal glutathione (GSH) and plasma aspartate aminotransferase (AST) following single or daily oral doses of aflatoxin B1 (AFB1, 2 mg/kg BW) or corn oil vehicle (1 ml/kg BW) were determined in male chickens (14-21-day-old). 2. Plasma AST and hepatic GSH increased 2 and 8 hr, respectively, following a single AFB1 dose. 3. Hepatic GSH continued to increase through 5 daily doses of AFB1, but there were no differences in AST levels on days 1-5. Feeding a diet containing 150% of NRC requirement for methionine attenuated the AFB1-induced increase in hepatic GSH. Renal GSH was unaffected by AFB1 or dietary treatment.

Aflatoxin B1↗

PubMed1991

Effect of glutathione manipulation on prostaglandin synthesis in renal medullary homogenates.

1. The effect of glutathione (GSH) manipulation on arachidonic acid (AA) metabolism in renal medullary (RM) homogenates was investigated. 2. Diethyl maleate (DEM) depleted GSH initially by 50% (P less than 0.05) and produced a general suppression (P less than 0.05) of all PGs with the exception of TXB2. GSH was further depleted during homogenization and a 30-min incubation period (P less than 0.01). 3. Adding glutathione monoethyl ester (GSH-MEE) (0, 0.8, 1.6 or 3.2 mmol/ml) to RM homogenates increased GSH (P less than 0.01) and decreased RM homogenates' PGs-synthesizing capability (P less than 0.05), with the exception of PGE2 and TXB2 at the highest concentration. 4. The results indicate that homogenization has a significant impact (P less than 0.05) on GSH concentration of the media and alterations in GSH concentration affect the profile and quantity of AA metabolites in renal medullary homogenates.

Animals↗

PubMed1991

Aflatoxicosis alters avian renal function, calcium, and vitamin D metabolism.

Experiments were designed to determine the effects of aflatoxicosis on avian renal function, calcium (CA), inorganic phosphorous (Pi), and vitamin D metabolism, and to determine if the effects of aflatoxin are reversible upon discontinuation of toxin administration. Three-week-old male broiler chickens (n = 12 per treatment) received aflatoxin (AF; 2 mg/kg po) or an equal volume of corn oil, the AF carrier vehicle, for 10 consecutive days. After 10 d of treatment, half of the birds from each treatment group were anesthetized and prepared for renal function analysis, which included a 2-h phosphate loading period. Ten days after discontinuation of AF treatment, the remaining birds in each treatment group were anesthetized and prepared for renal function analysis. AF decreased plasma 25-hydroxy vitamin D [25(OH)D] and 1,25-dihydroxy vitamin D [1,25(OH)2D] levels after 5 d of treatment. After 10 d of treatment, urine flow rate (V), fractional sodium excretion (FENa), and fractional potassium excretion (FEK) were lower in AF-treated birds. In addition, total plasma Ca tended to be lower (p = .10) and fractional Ca excretion (FECa) tended to be higher (p = .10) in the AF-treated birds. Intravenous phosphate loading produced a sharp increase in urine hydrogen ion concentration ([H+]) in the AF-treated birds. Glomerular filtration rate (GFR) was reduced and plasma osmolality was increased in AF-treated birds 10 d after discontinuation of toxin administration. The results indicate that AF directly or indirectly affects Ca and Pi metabolism in avians. At the present time, the effects may be related to altered vitamin D and parathyroid hormone (PTH) metabolism. Aflatoxicosis may decrease endogenous PTH synthesis and the renal sensitivity to PTH. The AF-related increase in urine [H+] during phosphate loading is probably due to increased Na+/H+ counterport, suggesting that AF stimulates sodium reabsorption. Also, the decrease in GFR exhibited 10 d after toxin removal indicates that AF may cause prolonged alteration in renal function.

Aflatoxins↗

PubMed1990

Altered renal function in broilers during aflatoxicosis.

Experiments were conducted to determine the effects of aflatoxicosis on acid-base balance, urine flow rate (V), glomerular filtration rate (GFR), clearance of para-aminohippuric acid (CPAH), plasma osmolality, and the renal handling of Na, K, Ca, and P. Three-week-old broilers were gavaged with aflatoxin at a dose of 2 mg/kg of BW per day for 10 consecutive days. Control birds received an equal volume of corn oil, the aflatoxin carrier vehicle. On the eleventh day, the birds were anesthetized and prepared for renal function analysis. A solution containing inulin, para-aminohippuric acid, and mannitol was infused at a low infusion rate (.1 mL/kg of BW per min) and a high infusion rate (.4 mL/kg of BW per min) to determine if aflatoxin affects the renal response to an acute volume load. Aflatoxicosis decreased the fractional excretion of phosphorous (FEP) and plasma Ca concentration but did not significantly alter any other renal function or acid-base variables. The decrease in FEP and plasma Ca may be a direct result of renal tubular damage, decreased Ca absorption from the gut, or a result of altered circulating levels of parathyroid hormone (PTH), and possibly decreased renal sensitivity to PTH.

Animals↗

PubMed1989

Physiological responses of heat-stressed broilers fed nicarbazin.

Two experiments were conducted to determine physiological responses in heat-stressed broilers fed a control diet or one containing 125 ppm Nicarbazin. Male birds were surgically implanted with a carotid catheter and fitted with a chest movement transducer and rectal probe. In Experiment 1, birds were exposed to an abrupt change from thermoneutral (22.5 C, 70% relative humidity [RH]) to heat stress (37 C and 40 to 50% RH) conditions within 10 min and maintained in this environment for 120 min. In Experiment 2, birds were exposed to a gradual change from thermoneutral to heat stress (38 C, 68% RH) conditions over 4 h and maintained in this environment for an additional 1 h. Heart rate (HR), respiration rate (RR), and body temperature (Tb) were monitored throughout each experiment, and arterial samples were obtained for determination of acid-base balance and lactate. Birds fed Nicarbazin had higher (P less than .05) Tb and lower (P less than .05) blood PCO2 and bicarbonate during heat stress than controls in both experiments. Thermal polypnea was observed in both experiments, but, although there were no treatment differences in Experiment 1, RR was lower (P less than .05) in the last hour of heat stress for Nicarbazin-fed birds in Experiment 2. In the second experiment, birds fed Nicarbazin exhibited higher (P less than .05) HR and blood lactate during heat stress than control-fed birds. The results of this study indicate that Nicarbazin, by an as yet unidentified mechanism, increases Tb in heat-stressed birds, which results in greater deviations in blood acid-base balance, blood lactate, and HR than in control-fed birds.

Acid-Base Equilibrium↗

PubMed1988

Effects of supplemental Bermuda grass hay or corn on intake, digestion and performance of cattle consuming endophyte-infected fescue.

Effects of supplemental Bermuda grass hay (BG) or ground corn on intake, digestion and performance of cattle consuming endophyte-infected fescue (I) were studied. In Exp. 1, a Latin square study, five growing Holstein steers (158.1 kg) consumed I ad libitum and were offered 0, .3, .6, .9 or 1.2% body weight (BW) of BG daily. Total dry matter (DM) intake rose linearly (P less than .05) with increasing BG, although intake was numerically similar with .6, .9 and 1.2% BW of BG. Digestibility was constant with diet (P greater than .10). Six growing Holstein steers used in Exp. 2, a Latin square with a 2 x 3 factorial arrangement of treatments, ingested I or noninfected (NI) fescue hay ad libitum with 0, .5 or 1.0% BW of ground corn. Total DM intake increased linearly as the level of corn rose (P less than .05). Total intake with I increased more with the first than with the second addition of corn, and the opposite occurred with NI (interaction between fescue infection and the quadratic effect of corn level, P less than .10). Organic matter digested (g/d) was greater for NI than for I and rose linearly with increasing corn ingestion (P less than .05). Ninety-six crossbred beef heifers and steers (184.2 kg avg initial live weight) were used in a 77-d fall grazing experiment (Exp. 3) with a 2 x 3 factorial treatment arrangement. Cattle grazed I or NI paddocks and were given no supplement or .34% BW of BG or .65% BW of ground corn on a daily basis (DM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

PubMed1988

Effects of frequency of offering and type of supplemental forage on intake and digestion in calves consuming endophyte-infected fescue hay.

Two experiments were conducted to determine the effects of frequency of offering and type of supplemental forage on intake and digestion in calves consuming endophyte-infected fescue hay (I). In Exp. 1, five Holstein steers, averaging 128 kg body weight (BW), were used in a 5 X 5 Latin square experiment. All steers were given free access to I in the afternoon. Morning meals consisted of 1) ad libitum access to I daily (control), 2) .5% BW of Bermuda-grass hay (BG) daily, 3) 1.0% BW of BG every 2nd d, 4) 1.5% BW of BG every 3rd d and 5) 2.0% BW of BG every 4th d. Steers receiving BG consumed less (P less than .01) I and more (P less than .01) total dry matter (DM) than did steers given I alone. Within treatment, I intake was similar (P greater than .10) among days of the feeding cycle without BG. Organic matter (OM) digestion was lower (P less than .05) with than without BG. In Exp. 2, 12 beef calves (Angus and Hereford X Angus; 6 mo of age, 155 kg initial BW) were used in a completely randomized-design experiment. Calves were given ad libitum access to I daily (control) or to BG or wheat hay (WH) on d 1 and I the following 3 d. Hay (I, BG or WH) intake d 1 of the feeding cycle was higher for BG and WH than for the control treatment (16 and 45%, respectively) and higher for WH than BG (25%; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

PubMed1987

Intake, digestion, passage rate and serum prolactin in growing dairy steers fed endophyte-infected fescue with noninfected fescue, clover or wheat straw.

Growing Holstein steers were used in two Latin-square experiments to determine the effects of supplementation of endophyte-infected fescue hay diets with other forages on intake, digestion, passage rate and serum prolactin concentration. In Exp. 1, five steers (average weight of 186 kg) were fed ad libitum amounts of endophyte-infected and noninfected fescue hays (I and NI, respectively) of similar quality in 0:1, 1:3, 1:1, 3:1 and 1:0 proportions. Total dry matter (DM) intake as a percentage of body weight (BW) linearly decreased .0055% for each 1% increase in dietary I (P less than .05). Dry matter intakes with 100% I and 100% NI diets were 2.13 and 2.72% of BW, respectively. Total tract digestion of neutral detergent fiber (NDF) increased linearly (P less than .05) with increasing I (66.0, 65.9, 66.3, 68.1 and 69.6%). Ruminal passage rate of particulates changed linearly (P less than .05) and quadratically (P less than .10) as I in the diet increased (3.5, 3.4, 2.6, 2.8 and 2.8%/h), while serum prolactin concentration and rectal temperature decreased linearly (P less than .05). In Exp. 2, four steers (average weight of 137 kg) were given ad libitum amounts of wheat straw (WS) or .73% of BW of clover hay (C) at 0800 and free access to either I or NI at 1600. Total intake as a percentage of BW was greatest for C with NI (3.04), intermediate for WS with NI (2.70) and lowest for C with I (2.30) and WS with I (2.23; P less than .05). Fescue intake (percentage of BW) was lowest (P less than .05) for C with I (1.56) and higher (P less than .05) for WS with NI (2.63) than WS with I (2.12); fescue intake for C with NI (2.33) was intermediate (P greater than .10) to WS with NI and WS with I. The results are interpreted to indicate that increasing the dietary level of I depressed intake linearly and markedly. Intake of diets high in I appears to be lower than can be explained only by ruminal-fill factors. When animals that are consuming basal I diets are provided access to nontoxic, high-quality forage, changes in intake may differ from those with basal diets of nontoxic forage.

Animal Feed↗

PubMed1987

Effects of offering different amounts and types of supplemental feeds to growing dairy steers fed endophyte-infected fescue hay ad libitum on intake, digestion, passage rate and serum prolactin concentration.

Ten Holstein steers (141 kg) were used in two 5 X 5 Latin-square experiments conducted simultaneously to determine the effects of offering different levels and types of feeds with endophyte-infected fescue given ad libitum. In Exp. 1, steers were given ad libitum access to infected fescue hay in the afternoon; in the morning fescue was given ad libitum (basal) or bermudagrass or clover hays were fed at .5 or 1.0% of body weight (BW). Supplementation did not affect total dry matter intake (P greater than .10), but supplementation at 1.0% of BW yielded total intake greater than supplementation at .5% of BW (P less than .05). Supplementation did not change digestibilities of dry or organic matter (P greater than .10). Particulate passage rate was greater (P less than .10) with supplementation at 1.0 than at .5% of BW, and increasing the level of supplementation from .5 to 1.0% of BW affected fluid passage rate positively with clover but negatively with bermudagrass (interaction, P less than .05). Serum prolactin increased (P less than .05) with all supplementation treatments, although no differences were observed between supplement type-supplementation level combinations (P greater than .10). Ground corn and wheat hay were supplements in Exp. 2. Total intake of dry matter was greater with supplements provided at 1.0 rather than at .5% of BW and for corn rather than wheat hay (P less than .05). Neutral detergent fiber digestion (percent of intake and grams per day) rose when wheat hay was offered at 1.0 vs .5% of BW but declined when the level of supplemental corn increased from .5 to 1.0% of BW (interaction, P less than .05). There were no differences among diets in particulate and fluid passage rates and serum prolactin concentration. Supplementation with nontoxic forage of a basal diet of infected fescue yielded intake substitution when forage was offered at .5% of BW, although incomplete substitution occurred with 1.0% of BW of supplemental forage such that total intake increased as compared to the lower level of supplementation.

Animal Feed↗