Preliminary observations on orgotein treatment of canine cataract.

In 2 clinical studies of canine cataract, mostly bilateral, intraocular injection of orgotein (Palosein: Diagnostic Data) was followed by varying degrees of clearing of lens opacity and return of functional vision in 39 of 56 dogs, most of which were given 1 injection (1.25 mg). First evidence of sight return and lens clearing was observed at 3-14 weeks post-treatment. In 2 dogs, clearing of cataract was followed by recurrence, and repeat treatment in one of these effected improvement. Although these results must be considered preliminary, in part because they relate to clinical cases not susceptible to controlled study, the apparent success rate suggests the feasibility of larger-scale studies under controlled conditions.

Aflatoxin effects with liquid crystalline cholesteryl esters of duckling sera.

An objective of this study was to determine indicator parameters of blood sera that are symptomatic for degenerative hepatic cholesterogenesis and lipid transformations induced with carcinogenic mycotoxins. A technique was developed for electrophoretic separation of liquid crystalline cholesteryl esters within beta lipoprotein fractions of duckling sera. These birefringent moieties decreased to 110 mug/mg low-density lipoprotein during 10-day bioassay periods for normal, nontoxin fed ducklings, but remained unchanged--179-189 mug/mg-for toxin-fed principals ingesting 0.988 mug aflatoxin/g feed throughout the bioassays. Their composition was principally cholesteryl esters with liquid crystalline characteristics determined by the oleate and linoleate content. Increased cholesterol levels--11.4% to 17.1% within sera of the nontoxin group--resulted in more frequent spherulitic mesoforms. The 0.9% to 1.8% taurochenodesoxycholate content within all sera samples induced stable cubic liquid crystalline forms. With polarized microscopy, cholesteric anisotrophs of sera were unique in composition and iridescent visage for each aflatoxin level regime. This specific dicroism was correlated with the corresponding hepatic histology.

Changes in adipose mass and cellularity through the adult life of rats fed ad libitum or a life-prolonging restricted diet.

Male Fischer 344 rats were either fed ad libitum (Group A) or 60% of the ad libitum intake (Group R) starting at 6 weeks of age; the latter is a life prolonging food restriction. Total adipose mass increased with increasing age in both Group A and Group R rats until about 70% of the life span after which it declined. The results indicate that the lower adipose mass of the Group R rats is probably not related to life prolongation. Adipocyte hypertrophy is involved in growth of the epididymal and perirenal depots in adult Group R rats and is the sole basis of epididymal depot growth in adult Group A rats. Increasing adipocyte number is the sole basis of perirenal depot growth in adult Group A rats and is involved in the growth of both depots in adult Group R rats. Decreasing adipose mass during senescence involves decreasing mean adipocyte volume but not a decrease in the adipocyte number.

In vitro and in vivo resistance of herpes simplex virus to 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine).

In vitro passage of the Patton strain of herpes simplex virus type 1 (HSV-1-P) in the presence of acycloguanosine (ACG) led to the emergence of a highly drug-resistant strain (HSV-1-P-ACG-R). Over 1% of virions in 6 of 15 HSV strains tested were able to form plaques in the presence of 10 mumol of ACG on first exposure to the drug. Therefore, there exists among HSV strains a broad range of susceptibilities to ACG, and some strains contain particles which are partially resistant to ACG before ever contacting the drug. HSV-1-P-ACG-R was partially resistant to iododeoxyuridine; conversely, iododeoxyuridine-resistant virus was highly resistant to ACG. ACG-resistant virus (HSV-1-P-ACG-R) was equal to its parent strain (HSV-1-P) in susceptibility to adenine arabinoside. The HSV-1-P-ACG-R strain produced corneal lesions in rabbits which were completely refractory to topical treatment with 1% unguent ACG, but responsive to 3% ACG. Partially resistant HSV could be isolated from the eyes of rabbits infected with ACG-susceptible virus and treated topically with either 1 or 3% ACG for 6 days.

Nutritional probe of the aging process.

It has long been known that food restriction markedly increases the length of life of rats and other laboratory rodents. It has been further shown that life-prolonging food restriction delays the occurrence or slows the progression of those diseases believed to limit the life span of the animal. However, the mechanisms responsible for this increase in longevity and for the delay in occurrence of age-associated disease are not known. Surprisingly little work hs been done on the effect of these life-prolonging dietary regimens on the many changes in physiological processes and biochemical characteristics that occur with age. Since biochemical and physiological explorations might well provide the information needed to investigate the basic mechanisms underlying these actions of food restriction, such a study was initiated in our laboratory. It was found that in most of the age-related functions studied changes were delayed or partially prevented by food restriction. Our studies provide a start in analyzing the mechanisms by which food restriction prolongs life and delays disease and it is to be anticipated that future research along this line will not only further define these mechanisms but in addition should greatly contribute to our knowledge of the aging process.

Susceptibility of BALB/cGnDu mice to transplantable tumors, in vitro transformed cells, BK and SV40 viruses, and chemical carcinogens.

Various oncogenic agents were employed in tumor susceptibility studies of an inbred subline of BALB/cGn mice, BALB/cGnDu, which carries a mutant gene that results in spontaneous thymic involution in homozygous recessive individuals. Of 18 transplantable tumors, 3 in vitro transformed cell lines, 2 oncogenic papovaviruses and 3 chemical carcinogens evaluated, only the Harding-Passey amelanotic melanoma produced tumors in 100% of the normal adult mice injected. The S180 pleomorphic sarcoma produced tumors in 56% of normal adult mice. Although not tumorigenic in adults, the mKSA, Morris (rat) hepatoma No. 7777, and a human papovavirus - transformed human cell induced mouse tumor line [GI110(BK) B6D2 Tu] formed tumors in 100, 62 and 70%, respectively, of recipients inoculated as neonates. SV40 and human papovavirus BK virions, as well as sV40, BK, and spontaneous in vitro transformed BALB/cGnDu cells were not tumorigenic. Although the histocompatibility antigens of these animals have not been studied, no correlations could be made between the tumor susceptibility of these animals with regard to the commonly employed inbred line BALB/c nor with regard to the range of host susceptibility of the transplantable tumors. This inbred subline represents a new strain of mice whose genetic defect makes it useful for transplantation immunology and physiological genetics.

Life span study of SPF Fischer 344 male rats fed ad libitum or restricted diets: longevity, growth, lean body mass and disease.

A life-span study was carried out on longevity, pathologic lesions, growth, lean body mass and selected aspects of muscle of barrier-maintained SPF Fischer 344 rats fed either ad libitum (Group A) or 60% of the ad libitum intake (Group R). Food restriction was as effective in prolonging the life of already long-lived SPF rats as previously shown for rats maintained in conventional facilities. Food restriction not only increased the mean length of life but also acted to extend life span since more than 60% of the Group R rats lived longer than the longest lived Group A rat. Renal lesions occurred at an earlier age in Group A rats than in Group R rats and progressed more rapidly. Death of most Group A rats was associated with severe renal lesions while few Group R rats showed such lesions at death. Food restriction was also found to delay or prevent interstitial cell tumors of the testes, bile duct hyperplasia, myocardial fibrosis and myocardial degeneration. Gastrocnemius muscle mass declined in advanced age and food restriction delayed this decline. Interestingly, however, lean body mass did not progressively decline with increasing age but rather decline occurred only after the onset of the terminal disease process.