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Biomedical subjects

D J Hoffman

Publications and source records attributed to D J Hoffman.

At least 19 recordsLinked to original sources
PubMed1996

Toxicity of seleno-L-methionine, seleno-DL-methionine, high selenium wheat, and selenized yeast to mallard ducklings.

The toxicity of four chemical forms of selenium (seleno-L-methionine, seleno-DL-methionine, selenized yeast, and high selenium wheat) was compared in day-old mallard ducklings (Anas platyrhynchos). In the first experiment, in which the basal diet was 75% wheat, survival after 2 weeks was lower for ducklings fed 30 micrograms/g selenium as seleno-L-methionine (36%) than for ducklings fed 30 micrograms/g selenium as seleno-DL-methionine (100%) or 30 micrograms/g selenium from high selenium yeast (88%). The concentration of selenium at 2 weeks in the livers of survivors was similar for ducklings fed 15 micrograms/g selenium as seleno-DL-methionine (12 micrograms/g, wet weight), seleno-L-methionine (11 micrograms/g), and high selenium wheat (11 micrograms/g), but was lower when the selenium came from selenized yeast (6.2 micrograms/g). When fed 30 micrograms/g selenium from the various sources, the selenium concentrations in liver were 20 micrograms/g for seleno-DL-methionine, 19 micrograms/g for seleno-L-methionine, and 9.9 micrograms/g for selenized yeast. In a second experiment, in which the basal diet was a commercial duck feed, survival after 2 weeks was 100% in ducklings fed 30 micrograms/g selenium as seleno-DL-methionine, seleno-L-methionine, or selenized yeast. Selenium concentrations in liver were similar for ducklings fed the 30-micrograms/g selenium diets as the DL or L forms of selenomethionine (27 and 25 micrograms/g), but lower for ducklings fed selenized yeast (13 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Method to estimate the rate and extent of intestinal absorption in conscious rats using an absorption probe and portal blood sampling.

PURPOSE: A variety of methods exist which determine the rate and extent of intestinal absorption. The method described here employs an internal absorption reference probe and portal blood sampling in unanesthetized rat. METHODS: Theophylline and tritiated water were selected as absorption reference probes since they are quantitatively absorbed in conscious rat. The fraction of an intestinal dose which reaches portal blood was determined from the resulting portal-systemic blood concentration gradients of the drug relative to the absorption probe. The absorption probes provide a means to calculate the drug mass reaching portal blood without the need of measuring the portal blood flow rate. The technique was evaluated with verapamil and a well-absorbed 5-lipoxygenase inhibitor, A-79035. RESULTS: The fraction of an intrajejunal dose of A-79035 reaching the portal vein (FG) was 0.86 using theophylline as the absorption probe. Verapamil, which is susceptible to extensive hepatic first-pass elimination, was completely absorbed (FG = 0.98) within 1 hour, but was only 21.4% bioavailable. Absorption rate constants, estimated from initial appearance rates in portal blood, were used to monitor factors that affect drug absorption. For example, with a dose solution containing 30% PEG-400, the absorption rate constants of theophylline and A-79035 were significantly reduced. Anesthesia reduced the absorption rate constant for theophylline in rats by 40% compared to conscious animals. CONCLUSIONS: The technique detailed here allows reliable, direct measurement of intestinal absorption which may assist in characterizing oral dosing for novel therapeutic agents.

Animals↗
PubMed1995

Effects of polychlorinated dibenzo-p-dioxins and dibenzofurans on nesting wood ducks (Aix sponsa) at Bayou Meto, Arkansas.

Wood ducks (Aix sponsa) nesting along Bayou Meto downstream from a hazardous waste site in central Arkansas were contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Residues in eggs, based on 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDD-EQ), ranged up to 611 parts per trillion (ppt), and egg arithmetic means were 90-fold higher at the site nearest the point source compared with a reference site. We monitored productivity of wood ducks in artificial nest boxes at three sites on the bayou and at a reference site on a separate drainage during 1988-1990. Productivity was suppressed (p < 0.05) at the bayou sites compared with the reference site, and egg TCDD-EQs were inversely correlated (p < 0.001) with productivity in corresponding nests. The threshold range of toxicity, where reduced productivity was evident in wood ducks (based on TCDD-EQs), was > 20 to 50 ppt. Oxidative stress and teratogenic effects occurred in ducklings at the more contaminated nesting sites nearest the point source. These findings suggest that wood ducks may be more sensitive to PCDD and PCDF contamination than some other aquatic birds and could serve as an indicator species for monitoring biological impacts from these contaminants.

Animals↗
PubMed1994

Protective effect of MgSO4 infusion on nmda receptor binding characteristics during cerebral cortical hypoxia in the newborn piglet.

This study tests the hypothesis that magnesium, a selective non-competitive antagonist of the NMDA receptor, will attenuate hypoxia-induced alteration in NMDA receptors and preserve MK-801 binding characteristics during cerebral hypoxia in vivo. Anesthetized, ventilated and instrumented newborn piglets were divided into three groups: normoxic controls were compared to untreated hypoxic and Mg(2+)-treated hypoxic piglets. Cerebral hypoxia was induced by lowering the FiO2 to 5-7% and confirmed biochemically by a decrease in the levels of phosphocreatine (82% lower than control). The Mg(2+)-treated group received MgSO4 600 mg/kg over 30 min followed by 300 mg/kg administered during 60 min of hypoxia. Plasma Mg2+ concentrations increased from 1.6 +/- 0.1 mg/dl to 17.7 +/- 3.3 mg/dl. 3H-MK-801 binding was used as an index of NMDA receptor modification. The Bmax in control, hypoxic and Mg(2+)-treated hypoxic piglets was 1.09 +/- 0.17, 0.70 +/- 0.25 and 0.96 +/- 0.14 pmoles/mg protein, respectively. The Kd for the same groups were 10.02 +/- 2.04, 4.88 +/- 1.43 and 8.71 +/- 2.23 nM, respectively. The Bmax and Kd in the hypoxic group were significantly lower compared to the control and Mg(2+)-treated hypoxic groups, indicating a preservation of NMDA receptor number and affinity for MK-801 during hypoxia with Mg2+. The activity of Na+, K+ ATPase, a marker of neuronal membrane function, was lower in the hypoxic group compared to the control and Mg(2+)-treated hypoxic groups. These findings show that MgSO4 prevents the hypoxia-induced modification of the NMDA receptor and attenuates neuronal membrane dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hypoxia-induced modification of the N-methyl-D-aspartate receptor in the brain of the newborn piglet.

The effect of hypoxia on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex in the brain cell membrane of the newborn piglet was studied. Experiments were conducted on newborn piglets, 2-4 days of age, that were anesthetized and mechanically ventilated. Hypoxic hypoxia was induced in the experimental group by lowering the FiO2 to 5-7%. The control group was ventilated under normoxic conditions. Tissue hypoxia was documented biochemically by decreased levels of ATP and phosphocreatine (PCr) in the hypoxic group (52% and 81% lower than the normoxic group, respectively). [3H]MK-801 binding characteristics (Bmax = number of receptors, Kd = dissociation constant) were used as an index of NMDA receptor modification. In hypoxic brains, Bmax decreased from the control level of 1.13 +/- 0.15 pmol/mg protein to 0.68 +/- 0.23 pmol/mg protein (P < 0.01) and the Kd value decreased (reflecting increased affinity) from 9.46 +/- 1.68 nM in the control brains to 4.87 +/- 1.42 nM (P < 0.01) in the hypoxic brains. The Na+,K(+)-ATPase activity, an index of brain cell membrane function, decreased from a control value of 46.5 +/- 0.4 to 40.5 +/- 2.3 mumol inorganic phosphate (Pi) mg protein/h (P < 0.005) during hypoxia. The results of this study indicate that hypoxia in newborn piglets modifies the NMDA receptor in the cerebral cortex, resulting in an increased affinity of the receptor channel. Hypoxia-induced modification of the NMDA ion/receptor complex may be a potential mechanism of cerebral excitotoxicity.

Adenosine Triphosphate↗
PubMed1994

Misalignment of pulmonary veins with alveolar capillary dysplasia: affected siblings and variable phenotypic expression.

Misalignment of pulmonary veins with alveolar capillary dysplasia is recognized as a rare cause of persistent pulmonary hypertension of the neonate. Until now, misalignment of pulmonary veins was thought to be a random occurrence, but its appearance in siblings at our institution suggests that there may be a familial predisposition. There have been reports of variable expression and variable severity in this disease; our report describes this variability in family members.

Abnormalities, Multiple↗
PubMed1994

Functional vision loss.

BACKGROUND: Functional vision loss (FVL) is a condition whereby a patient experiences a visual deficit without an organic or sensory basis. FVL is a diagnosis of exclusion, made only after organic pathology and sensory problems have been ruled out. METHODS: The authors reviewed the literature on FVL, delineated the etiologies and applied their clinical experience to the subject to provide the reader with a clinical appreciation and practical approach to FVL. This includes diagnostic strategies and etiology-based management. RESULTS: There are numerous sociopsychological etiologies of FVL of which the optometrist should be aware. Since FVL is a non-organic condition, the optimal treatment is usually multi-disciplinary, including a range of providers. CONCLUSIONS: The authors present an overview of FVL, classification of etiology, a diagnostic strategy, comanagement recommendations, and case reports.

Adolescent↗
PubMed1994

New England College of Optometry's impact on Boston neighborhoods.

BACKGROUND: In the 1960s, the city of Boston developed and implemented an innovative plan creating an urban primary health care system. This bold undertaking was predicated on the maximal utilization of a growing network of multidisciplinary neighborhood health centers. Almost concurrently, the New England College of Optometry (NEWENCO) began a total restructuring of its clinical curriculum. The objectives of this NEWENCO initiative were compatible with those of the city's health care restructuring plan. METHODS: The background, planning, structure, implementation and benefits of this collaborative effort are addressed. RESULTS: The two formed a unique partnership that elevated the quality of care for the residents of Boston's neighborhoods and dramatically improved the training experience for NEWENCO students. CONCLUSIONS: The NEWENCO-City of Boston partnership has improved the quality of health care in the urban neighborhoods and enhanced the clinical training of optometric externs.

Boston↗
PubMed1993

Effect of parity on periparturient neutrophil function in dairy cows.

Impairment of periparturient neutrophil function in dairy cows has been described. This may contribute to increased susceptibility of cows to bacterial infections during the periparturient period. Susceptibility to many complications of the postpartum period is influenced by parity. The aim of this experiment was to determine whether parity influenced periparturient neutrophil function in Holstein cows. Cows (n = 46, of which 26 were calving for the first, second or third time, and 20 were of more advanced parity) were sampled during the last prepartum week, the first postpartum week, 3 weeks postpartum and 6 weeks postpartum. Neutrophils were isolated by centrifugation and hypotonic lysis of erythrocytes. Neutrophil superoxide anion production was determined by the superoxide dismutase inhibitable reduction of ferricytochrome c, and stimulus-induced shape change was determined at 0, 30, 60 and 120 s after exposure to zymosan activated bovine plasma. Superoxide anion production was significantly depressed in the first postpartum week in all cows. At this time, superoxide anion production was significantly lower in cows in their fourth or greater lactation than in cows in the first three lactations. Neutrophil shape change responsiveness was also influenced by parity; immediately prepartum, the shape change responsiveness differed between groups at 120 s after application of the stimulus, and during the first postpartum week shape change responsiveness was less in cows of advanced parity at 30, 60 and 120 s after application of the stimulus. We concluded that cows in the fourth or greater lactation suffered more profound periparturient impairment of neutrophil function than younger cows and that this may be a factor mediating their increased susceptibility to some postpartum complications.

Animals↗
PubMed1992

Stabilization of the N-terminal residues of luteinizing hormone-releasing hormone agonists and the effect on pharmacokinetics.

To stabilize leuprolide (1) against chymotrypsin and intestinal degradation several agonists of LHRH (2-12), modified at position 1, 2, or 3 and/or containing N-alpha-methyl at positions 1, 2, or 4, were synthesized by SPPS. These agonists were tested in vitro for (a) rat pituitary LHRH receptor binding, (b) LH release from rat pituitary cells, (c) stability against chymotrypsin, and (d) stability against rat intestinal degradation. The clearances of the compounds in the rat were determined using a RIA. Complete stabilization against chymotrypsin (t1/2) and lumenal degradation (T1/2) was achieved with substitution of NMe-Ser4 in leuprolide; however, with an increase in clearance. Substitution with 1-Nal3 increased both t1/2 and T1/2, while substitution with NAc-Sar1 increased only T1/2. [NAcSar1,NMeSer4,D-Trp6,Pro9NHEt]LHRH (12), the doubly stabilized analogue, was tested in the rat by both iv and id administrations, and its bioavailabilities were measured. No significant improvement in id absorption over leuprolide was observed.

Amino Acid Sequence↗
PubMed1992

Interactive effects of selenium, methionine, and dietary protein on survival, growth, and physiology in mallard ducklings.

Concentrations of over 100 ppm (100 mg/kg) selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Both quantity and composition of dietary protein for wild ducklings may vary in selenium-contaminated environments. Day-old mallard (Anas platyrhynchos) ducklings received one of the following diets containing 22% protein: unsupplemented (controls), 15 ppm Se (as selenomethionine), 60 ppm Se, methionine supplemented, 15 ppm Se with methionine supplement, or 60 ppm Se with methionine supplement. In a second concurrent experiment the above sequence was repeated with a protein-restricted (11%) but isocaloric diet. In a third concurrent experiment all ducklings received 44% protein with 0, 15, or 60 ppm Se added. After 4 weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and histopathological lesions of the liver occurred. Antagonistic interactive effects occurred between supplementary methionine and Se, including complete to partial alleviation of the following Se effects by methionine: mortality, hepatic lesions, and altered glutathione and thiol status. With 11% protein, growth of controls was less than that with 22% protein, Se (60 ppm) caused 100% mortality, and methionine supplementation, although protective afforded less protection than it did with 22% protein. With 44% protein, ducklings experienced physiological stress, and Se was more toxic than with methionine-supplemented 22% protein. These findings suggest the potential for antagonistic effects of Se, methionine, and protein on duckling survival and physiology.

Analysis of Variance↗
PubMed1992

Interactive effects of arsenate, selenium, and dietary protein on survival, growth, and physiology in mallard ducklings.

High concentrations of arsenic (As) and selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Total biomass of invertebrates, a major source of protein for wild ducklings, may vary in environments that are contaminated with selenium. Day-old mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) containing 22% protein or diets containing 15 ppm Se (as selenomethionine), 60 ppm Se, 200 ppm As (as sodium arsenate), 15 ppm Se with 200 ppm As, or 60 ppm Se with 200 ppm As. In a concurrent experiment, the same sequence was repeated with a protein-restricted (7%) but isocaloric diet. After 4 weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and livers had histopathological lesions. Arsenic alone caused some reduction in growth. Antagonistic interactive effects occurred between As and Se, including complete to partial alleviation of the following Se effects: mortality, impaired growth, hepatic lesions and lipid peroxidation, and altered glutathione and thiol status. With 7% protein, survival and growth of controls was less than that with 22% protein, Se (60 ppm) caused 100% mortality, and As (200 ppm) caused mortality, decreased growth, and liver histopathology. These findings suggest the potential for antagonistic effects of Se and As on duckling survival, growth, and physiology with adequate dietary protein but more severe toxicological effects when dietary protein is diminished.

Animals↗
PubMed1991

Interactive effects of boron, selenium, and dietary protein on survival, growth, and physiology in mallard ducklings.

High concentrations of boron (B) and selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Total biomass of invertebrates, a major source of protein for wild ducklings, is sometimes diminished in agricultural drainwater ponds contaminated with Se and B. Day-old mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) containing 22% protein or diets containing 15 ppm (microgram/g) Se (as selenomethionine), 60 ppm Se, 1,000 ppm B (as boric acid), 15 ppm Se with 1,000 ppm B, or 60 ppm Se with 1,000 ppm B. In a concurrent experiment, the above sequence was repeated with a protein-restricted (7%) but isocaloric diet. After four weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and histopathological lesions of the liver occurred. Boron alone caused some reduction in growth. Several interactive effects occurred between B and Se, including further reduction in growth, and increases in plasma glutathione reductase activity, hematocrit, hemoglobin and plasma protein concentrations. With 7% protein, the growth of controls was less than that with 22% protein, 60 ppm Se caused 100% mortality, and growth effects of 15 ppm Se and 1,000 ppm B alone were more pronounced than with 22% protein. Selenium accumulation increased in the liver with 7% protein. Interactive effects were greater for Se and B with 7% protein than with 22% protein and included significant mortality and enhanced accumulation of Se in the liver. These findings suggest the potential for more severe toxicological effects of Se and B independently and interactively on duckling survival and development when dietary protein is diminished.

Animals↗
PubMed1991

Lead toxicosis in tundra swans near a mining and smelting complex in northern Idaho.

Die-offs of waterfowl have occurred in the Coeur d'Alene River system in northern Idaho since at least the early 1900's. We investigated causes of mortality and lead and cadmium contamination of 46 tundra swans (Cygnus columbianus) from 1987 to 1989; an additional 22 swans found dead in 1990 were not examined. We necropsied 43 of the 46 birds found from 1987 to 1989; 38 of these were from the Coeur d'Alene River system, which has been contaminated with mining and smelting wastes for a century, and the other 5 were from a nearby, relatively uncontaminated area. Of the 36 livers of swans from the contaminated area that were analyzed, 32 contained lethal levels of lead (6 to 40 micrograms/g, wet weight) and all birds exhibited several symptoms of lead poisoning, notably enlarged gall bladders containing viscous, dark-green bile. Only 13% of the lead-poisoned birds (10% when data were included from other studies of swans in the area) contained shot, compared to 95% of lead-poisoning swans in studies outside northern Idaho. Lead concentrations in blood samples from 16 apparently healthy swans (0.5 to 2.3 micrograms/g, and 4 lead-poisoned birds found moribund (1.3 to 9.6 micrograms/g) indicating that tundra swans accumulated high levels of lead from ingestion of sediment that contained up to 8,700 micrograms/g of lead and plants that contained up to 400 micrograms/g. The swans spend only a few weeks in the area staging during the spring migration. The five tundra swans from the uncontaminated area had low levels of lead and essentially no symptoms of lead poisoning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Subchronic hepatotoxicity of selenomethionine ingestion in mallard ducks.

Two-year-old male mallards (Anas platyrhynchos) received a control diet (0.2 ppm Se) or diets containing 1, 2, 4, 8, 16, or 32 ppm Se as selenomethionine for 14 wk. Se accumulated readily in the liver in a dose-dependent manner, reaching a mean concentration of 29 ppm (wet weight) in the 32 ppm group. Dietary Se of 2 ppm or greater increased plasma glutathione peroxidase activity. Mortality (10%) and histopathological effects, including bile duct hyperplasia and hemosiderin pigmentation of the liver and spleen, occurred in the 32 ppm group. These histopathological effects were accompanied by lower hemoglobin concentrations (16 and 32 ppm groups) and hematocrit (32 ppm group), and elevated plasma alkaline phosphatase activity (32 ppm group) indicative of cholestatic liver injury. Other manifestations of hepatotoxicity included significant linear dose responses for hepatic oxidized glutathione (GSSG) concentrations and ratio of GSSG to reduced glutathione (GSH). Means for both of these responses differed from controls in groups receiving 8-32 ppm Se. Mean hepatic GSH and malondialdehyde (a measure of lipid peroxidation) concentrations were significantly elevated in the 16 and 32 ppm groups. Subchronic effects of selenomethionine, which occurs in vegetation, are of particular interest with respect to the health of wild aquatic birds in seleniferous locations.

Alkaline Phosphatase↗
PubMed1991

Developmental toxicity of diphenyl ether herbicides in nestling American kestrels.

Beginning the day after hatching, American kestrel (Falco sparverius) nestlings were orally dosed for 10 consecutive days with 5 microliters/g of corn oil (controls) or one of the diphenyl ether herbicides (nitrofen, bifenox, or oxyfluorfen) at concentrations of 10, 50, 250, or 500 mg/kg in corn oil. At 500 mg/kg, nitrofen resulted in complete nestling mortality, bifenox in high (66%) mortality, and oxyfluorfen in no mortality. Nitrofen at 250 mg/kg reduced nestling growth as reflected by decreased body weight, crown-rump length, and bone lengths including humerus, radius-ulna, femur, and tibiotarsus. Bifenox at 250 mg/kg had less effect on growth than nitrofen, but crown-rump, humerus, radius-ulna, and femur were significantly shorter than controls. Liver weight as a percent of body weight increased with 50 and 250 mg/kg nitrofen. Other manifestations of impending hepatotoxicity following nitrofen ingestion included increased hepatic GSH peroxidase activity in all nitrofen-treated groups, and increased plasma enzyme activities for ALT, AST, and LDH-L in the 250-mg/kg group. Bifenox ingestion resulted in increased hepatic GSH peroxidase activity in the 50- and 250-mg/kg groups. Nitrofen exposure also resulted in an increase in total plasma thyroxine (T4) concentration. These findings suggest that altricial nestlings are more sensitive to diphenyl ether herbicides than young or adult birds of precocial species.

Animals↗
PubMed1990

New inhibitors of renin that contain novel phosphostatine Leu-Val replacements.

A novel series of renin inhibitors based on the Phe8-His9-Leu10-Val11 substructure of renin's natural substrate, angiotensinogen, is reported. These inhibitors retain the Phe8-His9 portion of the native substructure and employ novel phosphostatine Leu10-Val11 replacements (LVRs). The phosphostatine LVRs were prepared by condensing a dialkyl phosphonate ester stabilized anion with either N-t-Boc-amino aldehydes or N-tritylamino aldehydes (derived from the corresponding amino acid). Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine. The dialkyl ester moiety was varied and a loss in potency was incurred when the alkyl ester was chain extended or alpha-branched; dimethyl esters provided optimum potency. The phosphonate moiety was replaced by a half-acid half-ester phosphonate and dimethylphosphinate; both replacements lead to a loss in potency. The more potent inhibitors (IC50 = 20-50 nM) were found to be selective inhibitors for renin over porcine pepsin and bovine cathepsin D (little or no inhibition was observed at 10(-5) M).

Amino Acids↗