cle and joint pain. As the deficiency progresses, other signs appear, including gingival hemorrhage, loose teeth, subperiosteal hemorrhage, normocytic anemia, reduced serum iron concentrations, leukopenia, joint soreness, epiphyseal fractures with loss of bone substance, and exophthalmos (Tomlinson, 1942; Shaw et al., 1945; Greenberg and Rinehart, 1954; Banerjee and Bal, 1959a, 1959b; Ratterree et al., 1990; Eisele et al., 1992; Line et al., 1992). The signs of vitamin C deficiency are collectively called “scurvy,” and deficient animals are called “scorbutic.” Scorbutic rhesus monkeys excrete increased amounts of p-hydroxyphenyl compounds and keto acids in the urine when given test loads of tyrosine or phenylalanine, indicating abnormalities in tyrosine metabolism (Salmon and May, 1950; Rohatgi et al., 1958). Scorbutic animals have increased blood concentrations of glycoproteins and mucoproteins (Bandyopadhyay and Banerjee, 1964). Blood concentrations of nonprotein nitrogen and creatinine also are increased, and urine contains increased concentrations of nonprotein nitrogen and creatine (Rohatgi et al., 1958).

Gingival bleeding and fibrous gingival hyperplasia were reported in African green monkeys (Cercopithecus aethiops) deficient in vitamin C (De Klerk et al., 1973). Hydroxyproline concentrations were decreased in the gingiva, and synthesis of hydroxproline almost stopped in deficient animals; that suggests the lesions were caused by an inability to synthesize normal collagen (Ostergaard and Loe, 1975).

Squirrel monkeys (Saimiri sciureus) fed a vitamin C-deficient diet developed a characteristic subperiosteal hematoma, which progressed to a large swelling over the parietal area of the head (a cephalhematoma). In animals that were given ascorbic acid and recovered, the skull calcified, and this resulted in cranial hyperostosis. Cephalhematomas seem to be the primary diagnostic feature of vitamin C deficiency in squirrel monkeys (Lehner et al., 1968; Blackwell et al., 1974; Demary et al., 1978; Kessler et al., 1980).

Cephalhematomas are also seen in vitamin C deficiency in capuchin monkeys (Cebus apella) (Borda et al., 1996). However, capuchin monkeys also can exhibit all the traditional signs of scurvy, including weakness, joint tenderness, and extensive hemorrhages of the head, arms, and legs. Oral lesions develop, including necrosis of the gums, destruction of alveolar bone, and sloughing of the teeth (Shaw, 1949).

The common marmoset (Callithrix jacchus) has been shown to require a dietary source of vitamin C. Spontaneous physical mobility was decreased in deficient animals, and feed intake was reduced. Mean red-cell volume, packed red-cell volume, and red-cell counts decreased by about 10% overall, but hemoglobin concentration increased slightly. Vitamin C-deficient marmosets were generally free of clinical signs for 10 weeks, then suddenly became seriously ill, and many died within a few days despite therapeutic treatment with ascorbic acid. The disease was prevented by dietary vitamin C (Flurer et al., 1987). Extensive hemorrhages and loss of density about the periodontal ligament were seen, but the type of gingivitis seen in the rhesus monkey was not a prominent feature in the common marmoset (Driezen et al., 1969).

The white-lipped tamarin (Saguinus fuscicollis) and the common marmoset (Callithrix jacchus) appear to differ in their metabolism of vitamin C. When fed a diet ostensibly containing ascorbic acid at 2,000 mg·kg-1, the serum ascorbate concentration of the tamarins was about one-fifth that of the common marmosets (Flurer and Zucker, 1987). Stress appeared to increase the rate of ascorbic acid metabolism in both marmosets and tamarins, and there is some evidence that the difference in blood ascorbate concentrations was due to differences in susceptibility to stress between the two species (Flurer et al., 1990). It should be noted that the concentration of ascorbic acid in the diet at the time of feeding was not determined, and the stated concentration of 2,000 mg·kg-1 was based on the amount of vitamin C added before pelleting (Flurer and Schweigert, 1990).

There are wide ranges in the estimated ascorbic acid requirements of nonhuman primates. Table 7-6 summarizes the studies in which requirements were estimated. Day (1944) estimated that rhesus monkeys weighing less than 4 kg required 2.0 mg or less per day to prevent signs of scurvy; this estimate was based on calculation of vitamin C intakes from a number of published studies and was based primarly on the amount of orange juice required to prevent scurvy. Solv’ena et al. (1966) reported that a dose of 4 mg of vitamin C per animal per day protected monkeys weighing up to 4.3 kg from scurvy, but it did not prevent a drop in vitamin C concentrations in leukocytes and whole blood. Blood ascorbate is thought to reflect recent intake of ascorbic acid, whereas leukocyte ascorbate is a measure of the body’s reserve (Moser and Bendich, 1991; Turnbull et al., 1980). Machlin et al. (1976) administered vitamin Cat5mg·BWkg-1·d-1 to rhesus monkeys and observed a slow decline of blood ascorbate from 1.3 mg·dl-1 to 0.3-0.4 mg·dl-1. Increasing the ascorbic acid intake to 10 mg·BWkg-1·d-1 stopped the decline and prevented all signs of scurvy. Blood ascorbate levels fell to 0.3-0.4 mg·dl-1 in animals fed a natural diet furnishing ascorbic acid at less than 1.0 mg·BWkg-1·d-1, to render them deficient, but deficiency signs were mild and appeared only sporadically. More persistent signs were observed only when the animals were placed on a more deficient liquid purified diet. Working with cynomolgus monkeys, Tillotson and O’Connor (1980) found that adult and young monkeys required ascorbic acid at 3 and 6 mg·BWkg-1·d-1, respectively, to sustain blood concentrations of vitamin C. At that intake, leukocyte ascorbate concentrations, a measure of total body ascorbate, were minimal, indicating that the tissues were

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