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Biomedical subjects

R W Beaver

Publications and source records attributed to R W Beaver.

At least 19 recordsLinked to original sources

Fumonisin toxicosis in swine: clinical and pathologic findings.

From a series of experimental studies with pigs (12-16 kg), either pulmonary edema or liver failure emerged as a distinct pathogenetic expression of fumonisin B1 (FB1) toxicosis. The primary determinant as to which pathogenetic consequence developed was the quantity (dose) of the mycotoxin fed or intubated per kilogram of body weight per day. Pigs intubated with a minimum of 16 mg FB1/kg/day developed severe interlobular edema with or without hydrothorax and variably severe pulmonary edema. Pigs intubated with < 16 mg FB1/kg/day or pigs fed diets containing 200 mg FB1/kg of feed developed marked icterus and hepatocellular necrosis. The spectrum of degrees of severity of pulmonary edema observed in the experimental pigs allowed rational speculation regarding evolution of the pathologic changes.

Animals↗

Distribution of aflatoxins in tissues of growing pigs fed an aflatoxin-contaminated diet amended with a high affinity aluminosilicate sorbent.

The effect of hydrated sodium calcium aluminosilicate (HSCAS) added to the diet of swine fed an aflatoxin-contaminated diet on tissue aflatoxin levels was investigated. Pigs were fed control (less than 10 ng/g B1 + B2), contaminated (500-600 ng/g B1 + B2), and contaminated +0.5% HSCAS diets. Tissues analyzed for the presence of aflatoxin B1, B2, and M1 residues included liver, muscle, kidney, and adipose. Addition of HSCAS to the contaminated diet significantly reduced the amount of M1 in liver, kidney, and muscle tissue. Aflatoxin B1 was not reduced in liver or kidney, but was decreased in muscle.

Aflatoxins↗

Effect of a high affinity aluminosilicate sorbent on prevention of aflatoxicosis in growing pigs.

Adding 0.5% hydrated sodium calcium aluminosilicate to diets formulated with aflatoxin-contaminated corn significantly reduced the detrimental effects of the mycotoxin on live weight gains and feed intake. Hepatocellular changes normally associated with aflatoxin consumption could not be detected histopathologically in liver sections from pigs fed contaminated diets plus the aluminosilicate sorbent.

Aluminum Silicates↗

Canine aflatoxicosis: a continuing problem.

Aflatoxins are hepatotoxic in many species including dogs. In two separate outbreaks, the primary signalment was high morbidity and mortality in hunting dogs presenting with clinical signs of icterus, anorexia and listlessness. Preliminary laboratory examinations revealed toxic hepatitis, bilirubinuria and anemia. In the first case, a feed sample was not available and the diagnosis was established by confirming the presence of significant levels of aflatoxin B1 in tissues. In the second case, cornmeal utilized in formulating the ration contained 511 ng aflatoxin B1 and B2/g. These cases illustrate that aflatoxicosis is a continuing problem despite widespread awareness and testing for aflatoxin.

Aflatoxins↗

Synergism of hyperoxia and high helium pressures in the causation of convulsions.

Hyperoxia beyond 1.8 ATA results in a striking reduction of high-pressure neurological syndrome (HPNS) type I convulsion threshold pressures but is without measurable effect on type II convulsions. The synergism is partially or completely reversed by increasing alveolar or tissue CO2 levels. High total pressures (PI) result in striking reductions in the duration of hyperoxic exposure preceding seizure onset (tc). The interaction of hyperoxia and high pressure gives rise to three zones on the PO2-Pt plane. In zone I, Pt less than 30 ATA, the duration of hyperoxia prior to convulsion onset is given by the equation PO2 -- PO2 lim = K/(tc -- tc lim), where PO2 lim and tc lim both decrease with increasing total pressure. Zone II, Pt = 30-50 ATA and PO2 1.8-2.3 ATA, is characterized by a sharp drop in tc, as Pt is increased beyond 30 ATA, to a value near 15 min that is constant within the PO2 limits given. In zone III, Pt greater than 50 ATA and PO2 greater than 0.2 ATA, tc is of the order of 2 min, and the seizures are essentially HPNS seizures only slightly modified by hyperoxia. The data are interpreted as suggesting that zone I represents hyperoxic seizures facilitated by high pressures, whereas zone II represents HPNS type I seizures facilitated by hyperoxia.

Animals↗

Correlation studies of individual variation in susceptibility to various components of HPNS in mice.

Individual convulsion threshold pressures were determined in mice exposed successively to type I and type II convulsions of the high-pressure neurological syndrome (HPNS), as well as in others exposed, in successive compressions, to type I convulsions under diverse conditions of replication of compression rate. Correlation analyses of the results showed the following degrees of correlation of individual convulsion-threshold pressures: type I with type II-negligible (r2 less than equal to 0.2); type I with type I at the same compression rate-closely correlated (r2 greater than or equal to 0.8); type I with type I at a different compression rate-negligible (r2 less than or equal to 0.2). Individual susceptibility to HPNS (type I) convulsions thus is a stable characteristic of individual seizures vary independently of one another. Likewise, the magnitude of the individual compression rate effect varies independently of intrinsic individual susceptibility to type I HPNS seizures. The results support the view that the HPNS is a composite entity, define constraints on personnel selection, and provide a basis for estimating the efficacy of various selection strategies.

Animals↗

Comparative physiology of the high-pressure neurological syndrome--compression rate effects.

The effect of compression rate on onset of high-pressure convulsions has been studied in 14 vertebrate species, as well as in 10 mouse strains and 4 rat strains. Compression rate effects were observed in 9 of the 14 species. They appear to be independent of exposure temperature, correlate only very loosely with phylogenetic position, and appear to reflect species-specific compensatory mechanisms grafted onto an underlying convulsion-producing effect of high hydrostatic pressure. Five vertebrate species distributed among three of the four classes tested failed to show a significant degree of compression rate dependence of high-pressure neurological syndrome (HPNS) convulsion thresholds. The implications of this finding for the formulation of hypotheses regarding the biophysical basis for HPNS convulsions has been discussed. Comparison of intrinsic HPNS susceptibility in different species, in the light of these findings, requires that the comparison be made at a common compression rate. Four of the five lower vertebrate species fall consistently into the category showing high HPNS convulsion threshold pressures regardless of the compression rate employed, whereas the two primates and the one carnivore tested equally consistently fall in the low convulsion threshold pressure category. The data suggest a parallel between the degree of brain development and the relative HPNS susceptibility of a given species and contrast with the inverse relations observed during maturation of newborn mice and rats. The results are compared with data for other convulsants and suggest grouping HPNS and pentylenetetrazole seizures as against electroshock, hyperoxic, flurothyl, strychine, or picrotoxin convulsions.

Animals↗

Changes in heart rate associated with high-pressure convulsions in rodents.

The effect of compression in heliox atmospheres on heart rate in mice and in rats has been explored. In the absence of high-pressure neurological syndrome (NPNS) convulsions, the general relations between heart rate and pressure in mice from 14 days old to adulthood, as well as in 6- to 8-day-old rats, resemble each other, and also the results reported by others for liquid-breathing mice. Rats, 29 days old and adult, are different in that little bradycardia is observed. Type I (clonic) HPNS seizures are not associated with any additional changes in heart rate. Type II (tonic) seizures are invariably associated with profound transient bradycardia, recovery from which begins about the time the tonic seizure phase ends. The seizure-associated bradycardia can be abolished by atropine pretreatment. Data concerning relation of seizure-associated mortality, drug effects, and age and species differences are presented. The bearing of the results on the questions of seizure types in different species, neuroanatomical bases for HPNS seizures, and high-pressure death are discussed.

Age Factors↗

Time, rate, and temperature factors in the onset of high-pressure convulsions.

An interrupted compression profile technique was used to develop data to separate the effects of time and pressure factors governing increase of high-pressure neurological syndrome (HPNS) convulsion threshold pressures (the compression rate effect) during different compression profiles. A single differential equation fits all data available to date for compression rate effect on convulsion thresholds of CD-1 mice (three distinct types of compression profile; mean compression rates 12-1,000 atm/h). The process leading to increase in HPNS convulsion pressure is initiated at the very beginning of compression, proceeds at increasingly rapid rates as higher pressures are attained, and approaches a limiting upper convulsion pressure. The convulsion threshold pressure in any given experiment is independent of the compression rate prevailing during the time immediately preceding onset of the seizure. The magnitude of the compression rate effect in the CD-1 mouse is independent of chamber temperature over a range of 27-36 degrees C, and rectal temperatures of 29.2-37.5 degrees C. The bearing of these results on the design of optimal compression schedules and on the analysis of the neurological mechanisms underlying the HPNS is discussed.

Animals↗

Interaction of central nervous system effects of high pressures with barbiturates.

The interactions of phenobarbital, barbital, and pentobarbital with high pressures of heliox were explored. Principal features of the complex results include: double peaks in the time course of convulsion thresholds (Pc); an early peak and a shoulder in the time course of pressures reversing anesthesia (Pa); far steeper dose-response curves for Pa than for Pc; selectively greater anticonvulsant effect for phenobarbital than for the other barbiturates; and enhancement of Pa with simultaneous depression of Pc by reserpine in phenobarbital-pretreated mice. The data indicate the existence of at least two discrete sites of interaction between barbiturates and high pressure, reflected by Pc and Pa. The implications of the data for the development of biophysical theories of pressure reversal of anesthesia and anti-high-pressure neurological syndrome action of anesthetics are discussed, together with implications for the experimental study of convulsant and anticonvulsant agents, and their applications to underwater physiology.

Animals↗

Rate factors in development of the high-pressure neurological syndrome.

The effect of varying the pressure/time profile upon development of tremors and convulsions of the high-pressure neurological syndrome was studied in adult mice and squirrel monkeys and in baby mice. Two distinct response patterns were observed. In the adults rapid compression produces early onset of convulsions; convulsions subside rapidly when animals are held at constant pressure just above the convulsion point; and interrupted compression schedules show that total compression time rather than instantaneous compression rate at the moment seizures develop is the controlling parameter. Baby mice up to 12 days of age, by contrast, fail to show any perceptible relation between compression rate and convulsion threshold pressure (Pc); their seizures continue for a considerable period of time after a constant pressure level just above the convulsion threshold has been reached; and interrupted compressions of type a fail to change their convulsion threshold. Together with supplementary data regarding tremor thresholds and the transient increase of convulsion thresholds by prior seizures these results lead to a proposed schema describing these phenomena in terms of a pressure-dependent primary event predisposing to tremors and convulsions; a time-dependent event counteracting the convulsions (absent in baby mice); and a transient effect of prior convulsions, raising subsequent Pc.

Age Factors↗

Determination of aflatoxins in corn and peanuts using high performance liquid chromatography.

The various high performance liquid chromatographic techniques for the detection of aflatoxins in foodstuffs are examined. The need for resolution, selectivity, and sensitivity is emphasized and examples from the literature are used to illustrate this need. Examples include both normal and reversed-phase techniques. Sample cleanup, detection methods, chromatographic conditions, and pre- and post-column derivatization methods are discussed.

Aflatoxins↗

Comparison of an ELISA-based screening test with liquid chromatography for the determination of aflatoxins in corn.

An enzyme-linked immunosorbent assay (ELISA) screening test (CITE PROBE) was compared to liquid chromatography (LC) for the determination of aflatoxins in naturally contaminated corn samples. The CITE PROBE, with a positive/negative cutoff of 5 ng/g aflatoxin B1, was correct (based on LC results) on 47 of 51 samples. Two of the incorrect responses by the CITE PROBE were false positives on samples containing 4.4 ng/g and 4.1 ng/g aflatoxins by LC. Another incorrect response was a false negative on a sample containing 5.5 ng/g aflatoxins by LC. The fourth incorrect response was a false positive on a sample containing 1.9 ng/g aflatoxins by LC. On the basis of these results, the CITE PROBE was determined to be a reliable screening method for the detection of greater than or equal to 5 ng/g aflatoxins in corn.

Aflatoxins↗

Effects of injection solvent and mobile phase on efficiency in reverse-phase liquid chromatographic determination of aflatoxin M1.

The effects of injection solvent and mobile phase composition on the reverse-phase liquid chromatographic determination of aflatoxin M1 (M1) were examined. M1 was converted to the more highly fluorescent derivative aflatoxin M2a (M2a). Using a C-18 column and a mobile phase of H2O-MeCN-MeOH (60 + 20 + 20) (MP-A), M2a was dissolved in various ratios of MeCN-H2O prior to injection. Chromatographic efficiency for the M2a peak varied from ca 2000 theoretical plates when injected in 30% aqueous MeCN to ca 9000 plates when injected in water alone. However, using the same C-18 column but with a mobile phase of H2O-IPA-MeCN (80 + 12 + 8) (MP-B), the M2a peak exhibited 25,000 plates when injected in 30% aqueous MeCN and 10,000 plates when injected in water alone.

Aflatoxin M1↗