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Biomedical subjects

N Koppang

Publications and source records attributed to N Koppang.

At least 37 records · Page 2Linked to original sources
PubMed1983

Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. IV. Changes in the electroretinogram and the standing potential of the eye.

The present study correlates ultrastructural abnormalities in the retinal pigment epithelium (RPE) with electrophysiologic changes demonstrated in examinations of dogs with canine ceroid-lipofuscinosis (CCL) at various stages of clinical involvement using dc electroretinograms (ERG), including the c-wave, as well as recordings of the variations of the standing potential (SP) of the eye, both of which reflect the activity of the pigment epithelium. Normal c-waves and SP variations were seen at early stages of disease. At later stages, specific signs of pigment epithelial impairment were found in the form of (1) markedly reduced SP variations, (2) an increase in amplitude of the trough after the b-wave, and (3) a disappearance of the c-wave, which was replaced by a negative potential. These ERG changes correlate very well with a damaged pigment epithelium that generates the positive potential of the c-wave, as well as with normal Müller cells that generates the negative potential coinciding in time with the c-wave, and contributing to the trough after the b-wave. In the end-stage of the disease all potentials of the ERG were reduced drastically, evidently as a sign of cessation of neuroretinal function. Similarities between English setters with CCL and human Batten disease are discussed.

Animals↗
PubMed1982

Canine hereditary ceroid lipofuscinosis.

Dogs with an inherited form of ceroid lipofuscinosis are ataxic, blind and demented. During the disease process, they undergo severe cerebrocerebellar atrophy with storage of autofluorescent, lipid peroxide-positive reacting substances whose ultrastructure resembles 'fingerprint' patterns of membranous lamellae. The retina and RPE also undergo pathologic changes. Most important is the inverse relationship between loss of RPE melanin and increased deposition of ceroid. These pathological events in brain and eye lead to altered EEG, ERG and VEP activity. This inbred strain of English setters fulfills essentially all the criteria as a model for the human disease and will prove useful in the future for therapeutic trials.

Animals↗
PubMed1980

A survey of feeding N-nitrosodimethylamine (NDMA) to domestic animals over an 18 year period.

Sodium nitrite and formalin have been used as preservatives in the fish meal industry in Norway since 1953. In 1957, fur farms suffered losses of mink due to a new, malignant liver disease. Experimental feeding of herring meal to cows and sheep resulted in the death of some of the animals. Further studies showed that amines (TMAO) normally present in fish, can react with sodium nitrite used as preservative, or nitrogen oxides from the combustion of fuel oils used during processing, to produce the toxic agent, NDMA. Mink and fox may consume considerable amounts of fish meal in their diets. If the fish meal contains sufficient NDMA, the incidence of liver failure or tumours can be quite high. Long-term exposure to as little as 0.1 mg NDMA/kg b.w./day in the diet of mink, cows and sheep can produce fibro-occlusive changes in the hepatic vessels. These lesions can later cause capillary ectasies-like changes in cows, which are similar in appearance to hemangiomas seen in mink. The mink liver hemangiomas develop into hemangiosarcomas. We currently consider capillary ectasies-like changes in cows exposed to NDMA to represent pre-cancerous lesions.

Animal Feed↗
PubMed1980

Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. III. Morphologic abnormalities in retinal neurons and retinal pigmented epithelial cells.

Studies of the retina in 6- and 22-month-old English setters with progressive blindness, ataxia, and muscle weakness demonstrated a marked accumulation of abnormal cytosomes within neurons and retinal pigmented epithelial cells. Ganglion cells contained abundant cytosomes with evenly spaced stacks of membranes; bipolar and amacrine cell cytosomes consisted of dense, amorphous material with closely spaced configurations of light and dark lines; cytosomes within photoreceptor cells contained faintly staining curved profiles. All three cytosomes resembled those previously reported in brain neurons of CCL dogs. In retinal pigmented epithelial cells, there were prominent accumulations of lamellar fragments, either free in the cytoplasm or incorporated into melanin granules. These retinal abnormalities are likely to be related to deficiences of peroxidase and defects of lipid peroxidation. The pathologic and biochemical changes seen in these dogs are similar in many respects to those reported in human patients with Batten disease. As such, these dogs provide a convenient model for the study disease mechanisms and for therapeutic approaches to blindness in Batten disease.

Animals↗
PubMed1978

Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. II. The subcellular distribution of lysosomal hydrolases and other enzymes.

Observations on the progressive course of retinal degeneration in canine ceroid lipofuscinosis (CCL) showed dramatic changes in enzyme activity and subcellular compartmentation. Thus, in affected animals, a new particle containing high levels of hexosaminidase and galactosidase was found in fractions lighter than seen in controls. In the later stages of disease and in normal aging, a progressive increase in dense fractions with high titers of acid lipase and acid phosphatase was observed. Peroxidase was found predominantly in the heavier fractions (1.24 to 1.28 gm/ml) and was lower than normal in affected retina and RPE. These fractions were located above the pigment granule fraction. Changes of peroxidase activity in the pigment granules were age dependent in controls, but a decrease of similar magnitude occurred much earlier in affected dogs. The accumulation of large numbers of dense bodies in the retina and RPE in CCL may indicate an impairment of intracellular digestive mechanisms. The early and marked reduction of peroxidase activity in affected dogs is an important indicator for major changes in the biochemistry of the entire eye in this disease. Therefore the initial pathogenic event seems to be the inability of affected cells to cope with peroxidative damage at an early stage, followed by an exaggerated attempt by the cells to digest accumulating lipopigments.

Age Factors↗
PubMed1978

Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis, I. The distribution of enzymes in the whole retina and pigment epithelium.

The massive accumulation of autofluorescent lipopigments, representative of autoxidation, is a key morphological feature in canine ceroid lipofuscinosis (CCL). In the eye peroxidase, catalase, and four acid hydrolases were compared with regard to aged and clinical condition in a series of English setters affected with CCL. In unaffected English setters "soluble" peroxidase increased in the RPE to adult levels at 2 yr of age. Affected dogs had higher RPE peroxidase activity earlier in life, which then decline with age. The soluble retinal peroxidase of both unaffected and CCL dogs increased steadily with age, but the latter group of dogs were much lower in activity. By 2 yr of age, RPE and retinal peroxidase values were only 25% and 47% of unaffected dog levels. Although the soluble enzyme of unaffected dogs exhibited a maturational profile, membrane-bound RPE peroxidase showed a hyperbolic curve reaching a maximum at 10 mo of age. By 2 yr of age, the "bound" enzyme in affected dogs was below unaffected levels in the RPE and retina. Three acid hydrolases were slightly increased in the RPE and retina of affected dogs. Acid lipase activity, however, was similar in both unaffected and CCL dogs. Catalase was not found in the RPE of either group of dogs. The catalase activity in the retina of both affected and unaffected dogs was at similar levels. Since catalase is not present in the RPE, the major defense against peroxidase accumulation and peroxide toxicity probably depends upon peroxidase. The present study indicates that a decrease in this key regulating enzyme may be related to the formation of lipopigments in the retina and RPE of dogs with CCL.

Age Factors↗
PubMed1977

Detection of canine Batten disease with the EEG.

Although it has been suggested that EEG changes appear early in the course of human Batten disease, these observations have been made only after the onset of clinical abnormalities and without immediate pathological correlation. In this brief report we have been able to document for the first time, abnormal EEGs in a strain of dogs proposed as a model for Batten disease. The degree of abnormality in the canine EEG correlated with the degree of clinical involvement and with the presence of pathological inclusions, resembling those seen in human Batten disease. In younger dogs, abnormal EEGs were obtained even before clinical manifestations of the disease. The large amplitude discharges reported with photic stimulation in children with the late infantile form of Batten disease were not elicited in the dog model. However, this dog strain is a model for the juvenile rather than the late infantile form although similarities between dogs and both forms of human Batten disease were seen. It is proposed that the EEG is both a method for early detection of this disease as well as a tool ot measure the degree of involvement. This information may be of use in relation to future therapeutic trials.

Animals↗
PubMed1976

Toxic and carcinogenic effects of nitrosodimethylamine in mink.

In a feeding experiment, 96 mink divided into four groups were kept on diets in which each animal received from 0.04-0.07 mg/kg bw NDMA/day. After four months' feeding the mink were still in good health. Except for 20 mink kept for breeding, the animals were skinned. They showed no gross lesions; however, in the livers of mink receiving a total of 16-21 mg/kg bw NDMA some of the smaller hepatic veins were partially occluded. The 20 remaining mink and their offspring were all kept on the same diet, which included 10% herring meal with a NDMA content of 7.2-7.8 mg/kg. After 233 experimental days and a total intake of 26 mg/kg bw NDMA one male died of liver fibrosis and occlusive changes in the hepatic veins. The remaining 16 in the parent group and 22 in the F1 group developed haemangiomatous liver tumours after a total intake of 25-87 mg/kg bw NDMA. The carcinogenic action of NDMA on mink appears to be nearly 100% if the exposure time is long enough and if the dose is near to the hepatotoxic level.

Animals↗
PubMed1974

Dimethylnitrosamine--formation in fish meal and toxic effects in pigs.

The production of fish meal from fresh and from formaldehyde- and sodium benzoate-preserved catches results in the formation of considerable dimethylnitrosamine (DMNA). This is in contrast to the prevailing opinion that only nitrite preservatives can be incriminated in producing this toxin. With capelin fish preserved in a mixture of 920 g of sodium benzoate and 920 ml of formaldehyde/hectoliter for 11 days, 7.5 mgs of DMNA/kg fish meal were produced. Pigs exposed to different daily levels of DMNA, of commercial source, proved to be rather resistant to intoxication compared with other domestic animals. Doses of 100, 200 and 500 ppm of DMNA added to a commercial pig diet, with a cumulative ingestion of 8.1 to 13.9 g pig or from 282 to 583 mg DMNA/kg body weight, resulted in extensive vasoobstructive disease over a period of 64 to 105 days. These lesions are most severe in the liver where they produce a diffuse form of cirrhosis. Additional findings include anaplastic changes in the tubules of the kidneys. A DMNA level of 15 ppm in the feed, in this experiment from fish meal, did not result in pathologic lesions over an observation period of up to 525 days.

Animals↗