Growth changes in the craniofacial complex of the rat after prolonged papain administration.

The purpose of the study was to evaluate by radiographic and biometric means the effects of prolonged papain administration on growth of the craniofacial complex, to gain further insight into the importance of cranial cartilage for skull enlargement during rapid skeletal growth (25 to 70 days of age). Fifty 21-day-old male Lewis strain rats were divided randomly into three groups. Group 1 (n = 20) received 45 daily injections intraperitoneally of a 2% solution of crude papain in normal saline from 25 to 70 days of age. Group 2 (n = 20) were given 30 daily injections at the same dose level from 40 to 70 days of age, and group 3 (n = 10) served as untreated controls. Animals were weighted daily until 70 days of age and then every other day until killed at day 120. Submental-vertex and lateral skull radiographs were obtained at 25, 40, 53, 70, 90, and 120 days of age with standardized skull positioning and radiographic settings. Cephalometric measurements of 22 linear dimensions were made in each of 360 cephalograms, and the data analyzed statistically with Student's t test. Growth velocity curves were evaluated for evidence of catch-up growth. Body-weight gain by papain-treated groups was less than for controls (p < 0.001). Skull and nasal lengths, middle cranial base length, and sphenoidal length were significantly shorter (p < 0.001). Neurocranial length was also shortened, whereas neurocranial height and supraoccipital height increased. Reduction of skull dimensions was generally more pronounced in the earlier injected group.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphometric changes in growth of the rat pelvis after papain administration.

The proteolytic enzyme, papain, was given systematically to evaluate the short- and long-term effects of inhibition of endochondral bone formation on pelvic growth, with emphasis on the innominate bone. Ninety-eight Lewis-strain male rats, used concurrently for craniofacial growth studies, were divided into two groups. Thirty rats from Group I (n = 48) received 2% crude papain i.p. daily from 25-40 days-of-age and were euthanized at 40, 54, and 70 days-of-age. Thirty-five rats from Group II (n = 50) were given papain at the same dose from 25-70 days-of-age and were euthanized at 26, 40, 54, 70, and 120 days. The remaining animals in both groups were the controls. Standardized dorsoventral pelvic radiographs were taken of all 98 animals. Ten linear dimensions were measured on each and the data evaluated statistically. A reduction both in size and rate of growth of the bony pelvis was found. All the anteroposterior and most of the transverse pelvic dimensions were significantly shorter, to a greater extent in the prolonged papain group. Bi-ischial width was increased, perhaps to compensate for pelvic shortening and to accommodate the pelvic contents. The findings may contribute to our better understanding of abnormal endochondral bone growth in the pelvis.

Mandibular skeletal dysmorphology in micrognathic mice.

The primary manifestations of micrognathia were microglossia, midline fusion of the right and left sides of the mandible, total absence of incisor and molar toothbuds and, in many cases, absence or perhaps premature resorption of Meckel's cartilage. In addition, there was altered osteogenesis as evidenced by disrupted trabecular patterns, as well as an overall dimensional reduction of the mandible both antero-posteriorly and laterally. Strikingly similar results were reported by Johnson (1926), who studied the progeny of x-irradiated mice. How specifically our results correlate with this much earlier work is a matter for further analysis. It seems clear that the critical factor in the development of micrognathia is not so much an abnormal formation of the bony mandible, but a deficiency of tongue development, specifically its intrinsic musculature. Thus, mandibular micrognathia involves not only a dysmorphology of the first branchial arch, but also the mesenchymal cell migration from the occipital somites. Taken together, the picture is one that suggests an underlying cause that may have its inception at a much earlier developmental stage, when ectomesenchymal migration from the region of the neural tube occurs. In any event, we can report confidently that spontaneous micrognathia in prenatal mice is not a simple dimensional reduction of the lower jaw, but a more complex morphological phenomenon.