Effects of orthodontic force on enamel formation in normal and hypocalcemic rats

Maxillary incisors of young rats fed a diet deficient in calcium and vitamin D for 4 weeks developed hypoplastic enamel surfaces. In the enamel of maxillary incisors of deficiently fed rats as well as in normal rats, an orthodontic force (50 gm) acting on their incisors for 3-7 days induced foldings in the enamel, globular projections from the surface and marked hypoplastic defects. However, the orthodontic force produced clusters of free-lying enamel matrix only in the nutritionally deficient rats. In view of these observations, it might be concluded that disturbances in enamel formation which cause hypoplasias can be caused both by mechanical trauma and hypocalcemia. Furthermore, it seems that hypocalcemia increases the susceptibility to mechanical trauma of ameloblasts in their secretory stage. Whether the changes in enamel formation noted in the hypocalcemic rats is a direct effect of lowered serum calcium or due to the increase in parathyroid hormone is not known at present.     

Small intestinal peptidases and disaccharidases in rats with acute uremia

Acute uremia was induced in rats with temporary clamping of the left renal pedicle and contralateral nephrectomy. Jejunal peptidase activities (aminopeptidase N, dipeptidyl peptidase IV and aminopeptidase A), disaccharidase activities (maltase, sucrase, lactase and trehalase) and morphology were studied. A significant (p less than 0.05) increase in aminopeptidase N activity and a positive correlation between aminopeptidase N activity and serum urea was found in the uremic rats. The other peptidase activities showed a slight increase in the uremic rats. A shortening of the microvilli of the small intestinal epithelial cells in the uremic rats was seen by electron microscopy. The disaccharidase activities was unaltered. This study shows the presence of functional alterations in the small intestine in rats with acute uremia. The observations are also compatible with different regulation mechanisms for the brush border peptidases and disaccharidases.     

Degenerative joint disease in ballet dancers

Forty-four retired dancers were studied with regard to degenerative joint disease in the lower limbs. Six cases of coxarthrosis were found, significantly more than expected in the general population. In addition, there were four cases of tibio-femoral arthrosis, six of knee osteophytosis, four of patellofemoral arthrosis, three of chondrocalcinosis, and one of bilateral ankle arthrosis. More than one-half of the dancers had arthrosis in the metatarsophalangeal joints.     

Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth

Receptor tyrosine kinases of the Eph family are up-regulated in different types of cancer. EphB4 and its ligand ephrin-B2 have been linked to breast cancer, but little is known about how this receptor-ligand complex may contribute to oncogenesis. The Eph receptors transmit forward signals via their kinase domain and reverse signals via their transmembrane ephrin-B ligands. Therefore, we used EphB4 that were lacking the kinase domain and tagged with EGFP (EphB4 Delta C-EGFP) to differentiate between EphB4 and ephrin-B2 signaling. Interestingly, we found that expression of EphB4 Delta C-EGFP in breast cancer cells increases tumor growth in a mouse xenograft model. Given the undetectable EphB4 activation in the tumor cells, dominant negative effects of EphB4 Delta C-EGFP are unlikely to explain the increased tumor growth. Examination of the tumors revealed that ephrin-B2 is primarily expressed in the vasculature and that the EphB4 Delta C-EGFP tumors have a higher blood content than control tumors, concomitant with increased size of blood vessels. In support of an effect on the vasculature, the extracellular domain of EphB4 attracts endothelial cells in vitro and stimulates endothelial cell invasion, survival, and proliferation, all crucial factors for angiogenesis. These results support a model in which EphB4 promotes tumor growth by stimulating angiogenesis through ephrin-B2.     

Pharmacokinetics of digoxin in the turkey and comparison with other species

Digoxin was administered by bolus intravenous injection to seven broad-breasted white turkey poults at doses of 0.1, 0.15, or 0.2 mg/kg. Plasma digoxin concentrations were measured by a ¹²⁵ I radioimmunoassay at selected times over the subsequent 24 hr. The data were fitted to a two compartment open pharmacokinetic model. Overall mean values for kinetic variables were: distribution halflife, 38.96 min; elimination halflife, 11.03 hr; volume of distribution in the central compartment, 1.54 liters/kg; total body clearance, 5.81 ml/min/kg. Different doses did not appear to have a significant effect on the identifiable pharmacokinetic variables, suggesting that digoxin disposition is dose independent in the turkey. The results obtained in turkeys were compared with data reported for rats, cats, dogs, and humans. The value for total body clearance of digoxin in the turkey was similar to values found in man, dogs, and cats but considerably less than values reported for rats. The value for elimination halflife in turkeys was somewhat less than values reported for infants and dogs; however, it was considerably different than values reported for rats and cats.This work was supported in part by NIH Grant HL 18204 and the Dwan Family Fund.     

Carnitine alterations in spontaneous and drug-induced turkey congestive cardiomyopathy

Carnitine and acylcarnitines were measured in plasma and tissues of control turkeys, turkeys with an inbred spontaneous cardiomyopathy, and turkeys with furazolidone-induced cardiomyopathy. Heart failure was evident in both types of cardiomyopathy from decreased systemic blood pressure and cardiac dilatation compared to controls. Plasma free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine were significantly elevated by 76 to 614% (p less than 0.01) in the two cardiomyopathy models compared to control. The highest carnitine levels were found in the most hypotensive turkeys. Liver free carnitine and short-chain acylcarnitine levels were also elevated by 45 to 537% (p less than 0.05) in both types of cardiomyopathy. Free carnitine was elevated by 126% in left ventricle and by 54% in skeletal muscle of the furazolidone-treated turkeys (p less than 0.05). We speculate that hepatic synthesis of carnitine may be increased in response to hypotension and progressive cardiac dysfunction in cardiomyopathic turkeys. Such an increase may be useful to promote beta-oxidation of fatty acids as a cardiac energy source.     

Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy

³¹P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, ATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.

Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.

Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.

In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.