Donnell Creel

Inappropriate use of albino animals as models in research

Sensory-neural, biochemical-metabolic, and physiological anomalies occur in albino mammals. There are ontogenic and biochemical parallels between the senses, peripheral nervous system, endocrine glands, metabolism, and melanin pigmentation. All albino mammals examined have abnormal optic systems. Many drugs cannot be adequately evaluated in an albino model because of melanins ability to bind and interact with some chemicals. There is evidence that a general reduction in melanin pigment is correlated with a paucity of amino acids necessary for normal chemical function of the brain. There is a high probability that enzyme levels indicative of metabolic performance are deficient in the liver and kidneys oif albinos. Congenital defects are associated with hypopigmentation in animal models and human syndromes. Melanin is found in abundance in the eye, inner ear, and midbrain where neural impulses are initiated indicating a possible role as an electrophysiologic mechanism. Microwave irradiation differentially affects albino and pigmented animals. Implications of these observations and other reports of anomalies associated with hypopigmentation suggest caution in the use of albino and other hypomelanotic animals as normal models in biological research.

Effect of alcohol and task on hemispheric asymmetry of visually evoked potentials in man

The study examined the effect of a dose of alcohol producing a mean blood alcohol content of 90 mg% on components of the scalp-recorded visually evoked potential (VEP) both with and without a visual discrimination task to control the level of attention, and the interaction of amplitudinal hemispheric asymmetry of the VEP with alcohol treatment and the discrimination task. Ingestion of ethyl alcohol producing a mean blood alcohol content of 90 mg% affected VEPs recorded from the central scalp by attenuating the overall amplitude of the later VEP components (60-200 msec) and by significantly reducing hemispheric asymmetry in the amplitude of these VEP components. Alcohol attenuates VEP components P90-N120 and N120-P180, and the task of counting flashes and attending to discriminate double flashes increased amplitude of VEP components N60-P90 and P90-N120 in control and placebo conditions. Several studies have reported that the VEP recorded from the right hemisphere of human beings is larger than the VEP recorded from the homologous location in the left hemisphere. Evoked potentials recorded under control and placebo conditions in this study also demonstrated a hemispheric asymmetry with right larger than left for component P90-N120. We also found a reliable alcohol by hemispheric asymmetry interaction. Alcohol selectively depressed the amplitude of the right hemisphere VEP (P90-N120) component to a significantly greater extent than the left hemisphere VEP was affected.

Differences in visually evoked responses in albino versus hoded rats

Abstract Single and summed visually evoked cortical responses of albino and hooded rats were compared before and after monocular occlusion or enucleation to determine if differences in optic tract terminations between strains of rats could be detected by variation in the electrical input recorded at the cortex. Peak latencies were earlier in the hooded than the albino rat under all conditions. The minimum flash intensity at which primary components appeared in the summed evoked response was lower for the albino than for the hooded rat. The response contralateral to the intact eye following enucleation was of much larger amplitude, although no differences were apparent in the background EEG. The ipsilateral response was more like the contralateral response in the hooded than in the albino rat. The latter finding is consistent with anatomical and behavioral reports.

Differential susceptibility to noise-induced permanent threshold shift between albino and pigmented guinea pigs

Evidence that reduced levels of cochlear melanin are associated with increased auditory sensitivity, increased levels of auditory fatigue and an increased susceptibility to noise-induced hearing loss led us to investigate the effects of noise exposure on the cochlear microphonic (CM) in albino and pigmented English shorthair guinea pigs. CMs were recorded from the round window prior to and at 90 min and 7 days after exposure to 45 min of 126 dB noise. Thresholds for the first detectable elicitation of the CM for four pure tones were determined and the output voltage of each cochlea was measured in 10 dB steps through intensity levels which produced a maximum voltage amplitude in the CM and voltage rollover. This analysis demonstrated that: albino guinea pigs displayed significantly lower auditory thresholds than did pigmented animals before exposure to noise; thresholds were elevated to comparable levels in both groups 90 min after noise exposure; pigmented guinea pigs showed a reliable recovery in CM thresholds 7 days after exposure to noise while thresholds in the albinos remained elevated to the same degree at both 90 min and 7 days after noise; 90 min after noise exposure, the maximum voltage output of albino cochleas was significantly less than that recorded from the cochleas of the pigmented guinea pigs. These results demonstrate that albino guinea pigs are more susceptible to the ototoxic effects of high intensity noise than pigmented guinea pigs. Converging evidence indicates that some aspects of cochlear function involve melanin pigment and that its absence may produce auditory abnormalities. Reduced melanin pigmentation may also contribute to such phenomena as noise-induced threshold shifts and individual differences in noise-induced hearing loss.

Visually evoked responses in the rat, guinea pig, cat, monkey, and man

Abstract Visually evoked responses were recorded, before and after enucleation of one eye, from the visual cortex of rats, guinea pigs, and cats, and from the scalp of stump-tailed monkeys and human subjects selected from a population of men who had lost one eye. The evoked response of each species was unique with certain distinguishing characteristics. However, the visually evoked responses of the the rat and guinea pig were similar as were those of monkey and man, although the monkey generally lacked the late afterdis-charge activity often seen in the human response. Changes in the waveform of the visually evoked responses recorded from each hemisphere following ocular enucleation varied among species. These changes could be related to the proportion of nondecussating optic fibers and anatomical differences of the visual systems of the various species.

Retinogeniculostriate projections in guinea pigs: Albino and pigmented strains compared

Abstract The retinogeniculate fibers and geniculocortical projections of pigmented and albino guinea pigs were studied by anatomical degeneration methods and by electrophysiological techniques. In one experiment, an eye was enucleated from each of six pigmented and six albino animals. Six to δ days later the animals were killed and the crossed and uncrossed retinal projections to the dorsal lateral geniculate nuclei studied in serial sections prepared by the Nauta silver method. An organized uncrossed retinogeniculate projection was invariably present in the pigmented guinea pig but was not seen in the albino. There was a consistency in the pattern of the crossed retinogeniculate projections among the pigmented guinea pigs but not among the albino animals. Between ocular enucleation and histological analyses, visually evoked responses at the cerebral cortex were recorded. Indications of an input to the striate cortex via noncrossing fibers were found only in the pigmented strain. A relatively consistent pattern of input to the contralateral striate cortex was observed in the pigmented guinea pigs, while several patterns were seen in the albinos.

Auditory System Abnormalities in Human Albinos

Auditory abnormalities were evaluated in human albinos using temporary threshold shift and dichotic listening tasks. Albinos exhibited a greater temporary threshold shift than did normally pigmented individuals after exposure to a fatiguing tone. In the dichotic listening task, albinos demonstrated a significantly larger right ear advantage than normally pigmented individuals. These results support earlier work indicating that hemispheric asymmetries are present in the albino auditory system and suggest that abnormalities may be present at the cochlear level as well.

Albinism in Nigeria with delineation of new recessive oculocutaneous type

Seventy‐nine Nigerian oculocutaneous albinos were investigated. Fifty‐six had typical tyrosinase‐positive albinism (TPA) and 23 had brown albinism (BA), a new oculocutaneous type. The TPA were characterized by localized but no generalized skin pigment, yellow hair, blue to brown irides, nystagmus, and reduced or absent retinal pigment. Localized skin pigment included freckles and lentigines. The iris and skin pigment were the result of the slow accumulation of pigment with age as both were found in older individuals. The most severe skin changes were premalignant keratoses and squamous cell carcinoma of the skin, and the skin malignancies were the major factor in limiting the lifespan for TPA. The BA were characterized by generalized light brown skin pigment, light brown hair, blue to brown irides, nystagmus, and reduced retinal pigment. There was little accumulation or change of pigment in the eyes or skin with age. The generalized light skin pigment was effective in reducing sensitivity to solar radiation and very few BA had premalignant keratoses. Pedigree analysis for BA suggested an autosomal recessive inheritance pattern.

Effect of pharmacologically-induced arousal on the evoked potential in the unanesthetized rat.

Abstract Three positive-negative wave complexes of the visually evoked response (VER) in the unanesthetized rat were examined following iterative photic stimulation. EEG activation was induced by physostigmine, amphetamine, or pilocarpine in order to compare the peak latency and amplitude values of the VER components during arousal. It was served that the peak latency of only one component, a late negative wave occurring at approximately 160 msec was affected by the drug treatments. Except for one negative-positive amplitude measure occurring between 70 and 90 msec, the effect of drug-induced activation was to suppress the amplitude excursion of the remaining wave components. These observations agree with other VER studies in which arousal level was modified by type of behavioral task. It is suggested that the late negative wave peaking at 160 msec comprised the first wave of a photically evoked after-discharge burst.

Differential susceptibility to gentamicin ototoxicity between albino and pigmented guinea pigs

The known chemical affinity of melanin pigment for aminoglycoside antibiotics has led to the suggestion that higher concentrations of these drugs will bind to the pigmented inner ear and produce greater ototoxicity compared to the nonpigmented albino cochlea. Although this has provided a compelling hypothesis, results from the few investigations to address this question have been equivocal. In the present study, cochlear microphonic (CM) thresholds were recorded from albino and pigmented guinea pigs both before and two weeks after exposure for 14 consecutive days to 100 mg/Kg gentamicin. Cochleae were dissected and half-turn segments prepared for surface examination of the organ of Corti. After gentamicin exposure, threshold shifts averaged a statistically reliable 33 dB in albinos and 19 dB for the pigmented animals. Anatomical studies revealed a significant 44% mean outer hair cell loss in albinos compared to a 21% loss in the pigmented inner ears. The results showed that albinos display greater ototoxicity from gentamicin than do pigmented guinea pigs. Aminoglycosides are known to exert toxicity through interaction with polyphosphoinositides found in high concentrations in the inner ear. Cochleae in both albino and pigmented animals appear to possess significant phospholipid concentrations and bind toxic levels of these drugs independent of inner ear pigment content. However, evidence showing that melanin can inhibit aminoglycoside activity in vitro suggests that, once these drugs bind to pigmented tissue, they may undergo inactivation in a manner unavailable to the nonpigmented albino cochlea. The present results are consistent with the possibility that cochlear melanin may inhibit gentamicin activity in vivo and decrease the severity of aminoglycoside ototoxicity in the pigmented inner ear.