Hepatic regeneration and erythropoietin production in the rat.

The regenerating liver produces erythropoietin in response to hypoxia. The amounts of erythropoietin produced in animals subjected to hepatectomy are significantly higher than those observed in sham-operated animals. Hepatic erythropoietin production appears to be dependent upon the stage of regeneration with the highest levels being produced during the period of greatest proliferation and increase in liver mass.

The effects of x-irradiation on mouse palatal epithelial chromosomes.

Low levels of X-ray exposure of mouse palatal epithelial cell cultures resulted in increased numbers of chromosomal aberrations. At the lowest level used (IR), aberrations occurred of the type produced by two breaks such as chromatid exchanges, dicentrics, and metacentrics.

Isoproterenol-induced changes in cell cycle kinetics of parotid gland acinar cells in 8-day-old rats.

Isoproterenol (IPR) was shown to alter some parameters of the parotid gland acinar cell cycle in 8-year-old rats. Although the deoxyribonucleic acid (DNA) synthetic period (S) was decreased and the pre-DNA synthetic (G1) period was lengthened, there were no differences in the total cycle time. There was an increase in the 3H-thymidine labeling index from 35.7 to 50.8% combined with a decrease in the value of the mitotic index from 2.64 to 2.16% after IPR was administered. The results suggest that noncycling (G0) cells may be involved in the normal differentiation of the parotid gland and that IPR alters the transition of acinar cells between the cycling and noncycling state.

Mechanisms underlying the suppression of erythropoiesis by hyperoxia.

The possible mechanisms underlying the suppression of erythropoiesis in hyperoxic animals were studied. Male Long-Evans rats were injected with cobaltous chloride hexahydrate, a known erythropoietic stimulant. One group was exposed to a hyperoxic environment for ten hours. Both serum levels of erythropoietin (Ep) and renal levels of erythrogenin were significantly lower (p less than 0.005) in the hyperoxic animals compared to those left at room air. In addition, inhibitors to Ep or erythrogenin could not be detected in either the serum or renal tissue of the hyperoxic rats. These results indicate that the primary factor responsible for the erythropoietic suppression observed in a hyperoxic environment is a decreased production of erythrogenin which results in turn, in a lowered level of circulating Ep.

Recovery of an erythropoietin inducing factor from the regenerating rat liver.

The perfusion of livers of partially hepatectomized (H mean) rats lends support to earlier findings that the regenerating rat liver is the source of an erythropoietin-inducing hepatic factor (Ep-IHF) which stimulates hepatic production of extrarenal erythropoietin (Ep). Blood plasma was collected from perfused livers of rats that were partially hepatectomized (H mean) 48 to 72 hrs prior to perfusion with whole blood from normal rats. This plasma, when injected into normal rats which were nephrectomized (N mean) and rendered hypoxic 18 hrs after injection, evoked a significant increase in Ep values when compared to blood plasma collected from perfused livers of normal rats. Ep values were significantly higher when regenerating livers were perfused with blood collected from nephrectomized (N mean) rats than when such livers were perfused with blood of normal rats. The highest Ep values resulting from the liver perfusions were obtained when the liver donor and blood donor rats were both H mean and N mean. The results demonstrate that the liver is the principal source of an Ep-inducing factor since perfusion of the liver eliminated other potential tissue sources of activity in the rat. This was achieved by perfusing the livers directly through the portal vein and collecting the perfusate from the hepatic vein, thereby eliminating potential contributions from organs draining into other parts of the systemic circulation. In addition, it was shown that the kidney inhibits the activity and/or production of the Ep-IHF which is evoked by H mean.

A new organic solvent for use in the clearing of tissues. I. Soft tissue histology.

Histosol is a non-flammable solvent mixture of synthetic aromatic hydrocarbons with a flash point of 124 degrees F (T.C.C.). It has a lower vapor pressure and evaporation rate than other organic solvents, such as xylene, routinely used as clearing and deparaffinizing agents. Although both xylene and Histosol clear and deparaffinize soft organ tissues effectively in the preparation of permanently mounted stained slides, Histosol appears, in many instances, to be the choice solvent: tissues are easier to section; cell borders and cell surface modifications are most distinct; cytoplasmic eosinophilia is more vivid; and nuclear detail is improved. Of prime importance, Histosol is a safer and more efficient solvent for use in histological and pathological laboratories.

Histologic identification of mast cells in human dental pulp.

Previous investigators who attempted to identify mast cells in the dental pulp have used demineralizing or tooth-splitting procedures to obtain their tissue samples. However, Eda and Langeland15 found that the fluorescence of mast cells is destroyed by acid demineralizing agents. On the other hand, tooth splitting may damage the pulp by crushing it with forceps, or cutting and heating it with burs, stones, or discs. In the present study, we used the extirpated pulps from teeth in which endodontic access openings were made by means of high-speed rotary instruments with water spray. Metachromatic staining methods failed to demonstrate mast cells in any of the non-inflamed pulp specimens. Two of the inflamed pulp specimens revealed numerous mast cells which appeared intact and well preserved with no evidence of degranulation. As to the distribution of the mast cells, there was no correlation with the number and types of other inflammatory cells observed. Although several cells present in the specimens examined were suggestive of mast cells, only those cells that revealed definitive metachromasia were included in this study.

Composite materials for dental implants.

The requirements of endosteal dental implants are unique and stringent. The materials currently applied to implantation do not offer convincing evidence of satisfying these needs. This preliminary study reports on attempts at developing materials which would aid in obtaining a mucosal seal to maintain the integrity of the osseous, periosteal, and submucosal compartments from the oral environment and the attachment to bone as related to stress distribution. The materials that were under study were ceramic bonded to base metals and Dacron.

Hepatic erythropoietin (Ep) production following double partial hepatectomy in the rat.

Double partial hepatectomy (hepx) evokes an elevation in serum erythropoietin (Ep) levels in anephric hypoxic animals when compared to non-hypoxic or sham hepx controls. But this Ep response is significantly lower than that found in singly hepx, anephric hypoxic rats. Double hepx also induces numerous cytological changes in the liver. Extravascular accumulation of fat, fibrous scarring, localized necroses, and multiple abscesses, as well as decreased vascularity, occur following the second hepx. A humoral factor was detected in the serum of these animals that is capable of inducing hepatic Ep production when injected into normal rats 18 hours before nephrectomy and hypoxia. This factor, termed hepatopoietin (Hp), was previously demonstrated in the venous serum of singly hepx rats. The serum from animals subjected to double partial hepx is not as potent in inducing Ep production as the serum from singly hepx animals. The discrepancies noted between the single and double hepx groups is attributed to the necrotic cytological changes described above.

Evidence for a sexual variation in production of a hepatic erythropoietic factor by hepatectomized rats.

Erythropoietin (Ep) is a glycoprotein hormone that is responsible for mammalian red blood cell production. Adult rat liver regenerating 48-72 h after hepatectomy (hepx) produces elevated levels of Ep in response to hypoxia when compared to sham-operated, anephric hypoxic controls. A factor, termed hepatopoietin (Hp), found in the serum of hepx rats, is capable of stimulating hepatic Ep production when administered to normal rats 18 h prior to hypoxic exposure. Although the hepatic vein is the most potent source of this factor, Hp can also be demonstrated in the systemic arterial circulation. Bilateral nephrectomy (nephrx) of the donor hepx animal 24 h prior to bleeding abolishes this variation, and highest Ep levels are noted when serum from a hepx and nephrx rat is administered to animals immediatley after nephrx and 18 h before hypoxic exposure. Serum derived from hepx male rats displays a greater ability to evoke hepatic Ep production in normal recipients than serum from similarly treated female rats. Regardless of the sex of the hepx donor, Ep elaboration after hypoxia is highest in male recipients. The results indicate that there is a sexual variation in the production of Hp as well as Ep.

The effect of prostaglandins A2,E1,E2,15 methyl E2, 16, 16 dimethyl E2 and F2 alpha on erythropoiesis.

Prostaglandins A2, E1, E2, methylated E2s, and F2 alpha affected erythropoiesis and/or erythropoietin (Ep) production. This action is indicated in the exhypoxic, polycythemic mouse where radioiron incorporations into RBC increased after administration of these compounds. The kidney and liver have been indicated through previous studies, to actively participate in Ep production. The kidney and liver have been indicated through previous studies, to actively participate in Ep production. By the removal of one of these active sites in a murine system treated with prostaglandins it is shown that a response is reflected in Ep levels. Interference of the action of prostaglandins (PG) is altered by the removal of these target sites of Ep production. The erythropoietic responses elicited by PGA2, E1, and perhaps the methylated PGE2s act through the liver whereas PGE2 may operate through a renal pathway for its response. PGF2 alpha reveals no effect on erythropoietic activity and is no different than that observed for vehicle-treated controls. The prostaglandins tested appear to act primarily through the kidney or liver but the possibility exists that some yet undetermined organ site may also be involved.

Age-related variations in hepatic regeneration and erythropoietin production in the rat.

Erythropoietin (Ep) is produced mainly by the liver and spleen during fetal and neonatal periods and by the kidney during adolescent and adult life. The liver is also an important extrarenal producer of Ep in the hypoxic, anephric adult animal. Subtotal hepatectomy results in a substantial elevation in serum Ep levels at 30-72 hours after hepatectomy in rats subsequently nephrectomized and rendered hypoxic. Ep production is related to the mass of regenerating liver with peak Ep production occurring during times of greatest tissue proliferation. Regenerative and erythropoietic responses to hepatectomy decline with advancing age. Rats undergoing repeated hepatectomies do not recover full liver mass but the initial rate of regeneration increases following each successive hepatectomy. Ep levels decline in anephric hypoxic rats undergoing multiple hepatectomies when compared to sham-operated controls.

Reticuloendothelial system (RES) hyperfunction and erythropoietin (Ep) production in the regenerating liver.

Hepatic cells in rats were evaluated after subtotal hepatectomy using scintillation scanning with technetium sulfur colloid (TSC), autoradiography, and microstereology techniques. The ability of the liver to accumulate TSC increased during the course of the regeneration as did the labeling of Kupffer and parenchymal cells with tritiated thymidine (3H-tdR). Kupffer to parenchymal cell number ratios and Kupffer cell relative areas were also elevated, attaining peak values at 72 hours post-hepatectomy. This period corresponds to the time of peak erythropoietin (Ep) production in rats with regenerating livers after nephrectomy and exposure to hypoxia. These findings suggest that the Kupffer cell may function as a cellular site of Ep formation.

Biocompatibility evaluation of casting alloys in hamsters.

A number of base metal and low gold-content alloys were evaluated in hamster cheek pouches for biocompatibility. No adverse weight changes and no abnormal behavioral patterns were noted in any of the test groups over the 14-day period of the study. Gross examination of the cheek pouches containing the alloys was no different from that of the controls. None of the alloys tested showed significant adverse histopathologic reactions. The recorded changes in incidences and degree of response were essentially no different from those of the negative control material.