Ionomeric cement implants in the middle ear of the baboon (Papio ursinus) as a primate model

Faced with an inadequate supply of autogenous materials, the otologic surgeon may have to utilize various alloplastic materials to reconstruct bony middle ear structures. Allogenic materials have fallen into disfavor clinically because of the possible spread of infections. Implantation of the hybrid bone substitute ionomeric cement in viscous or hardened physical states into the middle ears of a primate animal model was undertaken in order to be able to approximate as closely as possible conditions found clinically. The posterior meatal wall was replaced by freshly mixed ionomeric cement in nine baboons (Papio ursinus). After repositioning the meatal flap, the residual skin defect was left to secondary epithelialization. After removal of the stapes superstructure, incus and malleus head, a columella of hardened ionomeric cement was trimmed to the appropriate size and inserted between the footplate and the malleus handle. In three cases the prosthesis shaft was fixed in position with freshly mixed cement near the footplate. The time of follow-up ranged from 47 to 277 days. Gross sections were obtained without decalcification (using a Zeiss saw microtome) and stained with Giemsa solution. In no instance was there any spontaneous epithelialization of the external meatus, although occasional granulation was seen to develop at the free edge of the flap and subepithelially. Epithelialization of the alloplastic columellae occurred as early as 42 days post-implantation. Over the middle ears reconstructed with the viscous cement, there was growth of a thickened epithelium that partially tended to granulate. On light microscopy, the bony footplate area was found to be unaffected by the cement that had been applied when still fluid. Our findings indicate that reconstruction of the posterior meatal wall with the viscous ionomeric cement can be useful clinically. The material does not become dislocated but, as with all other alloplastic materials, spontaneous overgrowth of the adjacent meatal skin is unlikely to occur. The early epithelialization of the columellae and their middle ear compatibility and biostability give support to the excellent tolerability of the ionomeric cement. At present, complications occurring during otoneurological application of the material necessitated its commercial withdrawal from the market in May 1995.     

The effect of ascorbic acid on the activity of lipoprotein lipase in the baboon (Papio ursinus)

The intravenous administration of heparin-released lipoprotein lipase (LPL) into the circulatory system of the baboon (Papio ursinus) is described. After a single heparin injection, a peak value of LPL activity appeared in the circulation with 5 minutes. At low doses of heparin (less than 100 units heparin/kg body mass), LPL disappeared from the circulation in an exponential fashion with a half-life of about 20 minutes. An increase in the heparin dose increased the amount of LPL released into the circulation. In baboons which were deficient in ascorbic acid, less LPL was released into the circulation after specific doses of heparin than in animals that were amply supplied with this vitamin (ascorbic acid 16 mg/kg body mass/day). The separation of plasma LOL, released by heparin, on Sephadex G-150, revealed several distinct molecular species of LPL in the eluant from the columns. In vitro studies indicated that ascorbic acid inhibited cardiac LPL strongly, whereas it had little effect on "post-heparin plasma" LPL. 2somolar concentrations of another reducing agent, mercapto-ethanol, slightly stimulated cardiac LPL in baboons.     

Late luteal rescue in the baboon (Papio cynocephalus)

At the Department of Dental Radiology of ACTA, the line fraction deviation (LFD) method was developed to measure orientation on radiographic trabecular patterns. This article explains the measurement of the LFD index of orientation in a downscaled model. When investigations began to produce noteworthy results, the need for deeper understanding of the method and the resulting diagrams increased. Because it had previously been applied on rather complex patterns originating from bone it seemed worthwhile to study simpler images as well, which might yield a more intuitive understanding of the diagrams. Moreover, it seemed useful to compare the new LFD method with the well-accepted mean intercept length (MIL) method. Fifty images originating from cancellous bone structures and 25 drawings were analyzed. The results show that the MIL method tends to produce ellipses (not only on images originating from bone), and also that the LFD method is more sensitive to anisotropy.     

The metabolism of cortisol by term baboon neonates (Papio papio)

The metabolism of iv administered (4-14C)cortisol (F) was examined in 3 female, spontaneously delivered, term baboons less than 24th old. Sixty and 80% of 14C was recovered in urine within 24 and 68 h,respectively. The distribution of urinary 14C was 44.7% unconjugated, 18.1% glucuronoside, 3.3% sulfate, and 24% unextractable with ethyl acetate. The metabolites were isolated by chromatography and crystallization. Eight per cent of unconjugated and 60% of glucuronoside metabolites were more polar than the cortols, the majority being unknown I (Rf 0.15), and unknown II (Rf 0.35), (csf., 6beta-ol-F), Rf 0.44, ethyl acetate-chloroofrmmethanol-water, 25:75:50:50). Unconjugated cortisol plus cortisone (E) represented less than 1% or urinary 14C and tetrahydrocortisone (THE) glucuronoside represented 1.2%. Excretion of tetrahydrocortisol (THF) and products of side-chain cleavage were negligible. Excretion of 20beta-hydroxy metabolites and 6beta-ol-F was less than or equal to 5% of urinary 14C. The cortisol production rate (mean +/- SE) calculated from the specific activity of THE was 4.95 +/- 1.92 mg/day. The glucuronoside/unconjugated 14C-ratio (0.4) contrasts with those previously reported in nonpregnant (4.0), pregnant (1.0), and postpartum (1.3) animals, indicating that the metabolic pattern in newborns is an exaggeration of that in pregnancy. In neonates, unknown I and II compensate quantitatively for decreased glucuronoside excretion. Unknowns I and II are derivatives of THF and THE, suggesting that increased hydroxylase or deficient glucuronyl transferase, rather than impaired delta4-reductase, is responsible for decreased glucuronoside excretion. The low F production rate, reduced glucuronoside formation, and increase in highly polar compounds relative to nonpregnant adults resemble the situation in humans. However, the reduction in glucuronosides is compensated for, quantitatively, by highly polar metabolites, which are extractable from baboon urine with ethyl acetate but are nonextractable from the urine fo human neonates.     

Comparative studies on the in vitro decidualization process in the baboon (Papio anubis) and human

Blood supply is essential for the maintenance of epididymal function. Since there is no considerable neovascularization in the epididymis, this tissue could represent a suitable model to study the vascular endothelial growth factor (VEGF) effect for vascular permeability. We studied the expression and function of VEGF and its receptors fms-like tyrosine kinase (Flt-1) and fetal liver kinase (designated as kinase insert domain-containing receptor, KDR in the human) in the human epididymis. VEGF and VEGF receptors mRNA were detected in the human epididymal tissue. VEGF protein was localized in peritubular and in ciliated cells of efferent ducts as well as in peritubular and basal cells of the epididymal duct. Vascular endothelial cells did not express VEGF. Flt-1 protein was localized in ciliated cells of efferent ducts and in lymphatic vessels. Vascular endothelial cells were negative for Flt-1 but positive for KDR. In vitro VEGF165 treatment of epididymal tissue induced endothelial fenestrations and opening of interendothelial junctions. Additionally, we observed for the first time that VEGF could induce transendothelial gaps. We conclude that these gaps might be of importance not only for molecular transport but also for cell passage across the vessel wall, which may be significant for tumor metastasis. VEGF may act as a paracrine effector to influence the permeability of lymphatic vessels via Flt-1, and of blood vessels via KDR.     

The effect of dexamethasone administration at different stages of gestation on maternal plasma steroid concentrations in the baboon (Papio cynocephalus)

Dexamethasone administration at different stages of gestation in the baboon was studied for its effect on maternal steroid hormone concentrations. Dexamethasone (2 mg i.m. at 12 h intervals for three doses) was administered at early (days 37-39), mid (days 76-85) or late (days 112-123) gestation and morning blood samples were collected before, during and after dexamethasone suppression for 6 consecutive days. Dexamethasone treatment, at all stages of pregnancy, resulted in a significant decline in maternal serum cortisol concentrations, which rapidly return to normal concentrations after treatment. Progesterone concentrations were not affected by dexamethasone at any stage of gestation. Serum concentrations of oestradiol, testosterone and androstenedione were unchanged following dexamethasone administration in early pregnancy. A trend toward lower serum oestradiol was observed following dexamethasone administration in both mid and late gestation, but this was not significant. Both testosterone and androstenedione were significantly decreased following dexamethasone in both mid and late pregnancy and recovered to pretreatment concentrations within a few days after cessation of treatment. These results confirm other studies which demonstrate that adrenal precursors (maternal or fetal) are a major contributor to maternal serum concentrations of oestradiol. They also demonstrate that these adrenal precursors increase serum concentrations of testosterone and androstenedione in the pregnant baboon. Since these changes are only evident after that time (>40 days) when the fetal adrenal is steroidogenically competent, a role for fetal adrenal involvement in maternal serum androgen concentrations is suggested.     

Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques

Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.     

Modified Küntscher's nail for the proximal femur fixation after corrective osteotomies in children (author's transl)

The authors describe the development in the design of the modified Küntscher's nail with two fins on its upper part, assigned for the fixation of proximal femur after corrective osteotomies in children. Detailed explanation about the nails construction and its biomechanical characteristics are presented. The fixation of the nail in the proximal and distal femoral part, as well as on the site of osteotomy is particularly analyzed. On the base 423 operated cases, where the modified Küntscher's nail was applied, the authors conclusion is that the nail is very suitable for the correction of proximal femur deformities in children.     

Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor localization in the baboon (Papio anubis) oviduct during steroid treatment and the menstrual cycle

OBJECTIVES: Polypeptide growth factors may modulate the actions of estrogen (E2) and progesterone (P) in reproductive tissues in an autocrine/paracrine manner. The objective of this study was to determine whether the baboon oviduct contains epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and EGF receptor (EGF-R) and whether changes in their expression are correlated with various hormonal states. METHODS: Oviductal tissue was obtained from adult female baboons (Papio anubis) after oophorectomy and steroid treatment, and during the menstrual cycle. Ampullary regions were fixed in Bouin's fixative and embedded in paraffin for immunocytochemistry using rabbit polyclonal antibodies against EGF and EGF-R, and mouse monoclonal antibody against TGF alpha. RESULTS: Both EGF and EGF-R were present in all tissue compartments (most strongly in the epithelium, followed by smooth muscle and stroma) at all reproductive stages and showed similar staining patterns. However, the most intense immunoreactive product was found in the tissue obtained from the E2-treated and late follicular phase animals. At this time, intense staining was present in the apical regions of the mature ciliated cells, whereas the stain was dispersed uniformly over the cytoplasm of all other cell types. Immunoreactive TGF alpha was limited primarily to the nonciliated epithelial cells, and staining was most intense in the E2-treated and late follicular phase tissues. Transforming growth factor-alpha formed intense perinuclear deposits in the mature secretory cells, an area that corresponds to the Golgi region. No immunoreactive product was observed for any of these proteins when preimmune serum was substituted for the primary antibody or when the primary antibody was preabsorbed with antigen. CONCLUSION: In summary, EGF, TGF alpha, and EGF-R are present in the ampulla of the baboon oviduct. Moreover, the localization and intensity of immunoreactive product are dependent on cell type and hormonal state. These data are consistent with the concept that EGF, TGF alpha, and EGF-R may be regulated by E2 and P and thus may play a role in cell differentiation and function. In addition, the specific localization of TGF alpha suggests that this growth factor may be synthesized for release from the secretory cells and thus may also function as a modulator of gamete/embryo viability and development.     

Disappearance of the ovulation stigma in baboons (Papio anubis, Papio cynocephalus) as determined by serial laparoscopies during the luteal phase

OBJECTIVE: To investigate how long an ovulation stigma remains visible as determined by serial laparoscopies performed during the luteal phase in baboons. SUBJECTS AND SETTING: Sixteen female baboons with a normal pelvis (n = 6) and with endometriosis (n = 10) housed at the Institute of Primate Research, Nairobi, Kenya. INTERVENTIONS: Fifty-six laparoscopies were carried out before ovulation (n = 7) and serially during the luteal phase (n = 49; 3 +/- 1 per baboon): 1 to 2 days (n = 2), 4 to 5 days (n = 15), 8 to 9 days (n = 11), 12 to 13 days (n = 12), and 16 to 17 days (n = 9) after ovulation. MAIN OUTCOME MEASURE: During each laparoscopy the ovaries were screened systematically for the presence and size of an ovulation stigma and/or corpus luteum (CL). RESULTS: When the laparoscopy was done within 5 days after ovulation, a fresh ovulation stigma was observed in all nine baboons with a normal pelvis or minimal endometriosis, but only in four of seven animals with mild to severe disease. If a fresh ovulation stigma had been observed within 5 days after ovulation (n = 13), it gradually became smaller but remained visible 8 to 9 days after ovulation in 91%, at 12 to 13 days after ovulation in 75%, and at 16 to 17 days after ovulation in 50% of the primates. CONCLUSION: If a fresh ovulation stigma was observed in baboons within 5 days after ovulation, it diminished in size but remained visible up to 8, 12, and 16 days after ovulation in 91%, 75%, and 50% of animals, respectively. Therefore, diagnostic laparoscopies for the detection of an ovulation stigma in baboons should be performed in the early luteal phase.     

Blood flow and vascular pressure in the dental pulp. Summary

The present summary is a review and a discussion of the following papers (I-V), submitted as partial fulfillment of the requirements for the degree of Doctor Odontologiae at the University of Bergen. I. Blood flow in the dental pulp in dogs measured by local H2 gas desaturation technique. Arch. Oral Biol. 1975, 20, 73-79. Co-author: K. Aukland II. The effect of variations in arterial blood pressure and baroreceptor reflexes on pulpal blood flow in dogs. Arch. Oral. Biol.1975, 20, 345-349 III. Effect of vasodilating drugs on external carotid and pulpal blood flow in dogs: "Stealing" of dental perfusion pressurE. Acta Physiol. Scand. 1976, 97, 75-87 IV. Nervous control of blood flow in the dental pulp in dogs. Acta Physiol. Scand. 1978, 104, 13-23. Co-author: G. Naess V. Microvascular pressure in the dental pulp and gingiva in cats. Acta Odontol. Scand. 1979, 37, 161-168. Co-author: G. Naess Other papers are referred to in the conventional manner.     

Reactivation of Delta-Notch signaling after injury: complementary expression patterns of ligand and receptor in dental pulp

We have developed a unique in vitro reconstitution system for tracheal epithelia of guinea pigs. In the system, a human amnion membrane was used as a basement membrane and the tracheal epithelial cells were cultured on the epithelial side of the membrane. Three weeks later, the tracheal fibroblasts were co-cultured on the serosal side of the amnion membrane and the culturing was continued for an additional 10 d. The morphology of the cultured epithelial cells consisted of a pseudostratified columnar ciliated epithelium from cuboidal ciliated epithelium during the last 10 d of the culture period. Epithelial cells included both goblet-like and basal cells. In addition, the frequency of each type of differentiated cells was almost identical to that of in vivo tracheas. Interestingly, the same results were obtained when the conditioned medium of the tracheal fibroblasts was used instead of the fibroblasts themselves. These results suggest that epithelial-mesenchymal interaction is likely involved in growth and differentiation of epithelial cells in vivo in a soluble factor(s)-mediated manner. As well as the epithelial cells, the fibroblasts also formed a multilayer during the last 10 d of co-culturing. This indicates that in vitro reconstitution of tracheal epithelia is achieved without addition of any exogenous growth or differentiation factors. The reconstitution system is shown to be useful for investigating the cellular and molecular interaction of epithelial and mesenchymal cells. Possible applications of the culture system and possible factors involved in growth and differentiation of epithelial cells are discussed.     

Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease

OBJECTIVE: To test the hypothesis that spontaneous endometriosis is a progressive disease in baboons. DESIGN AND SETTING: Prospective cohort study, Institute of Primate Research, Nairobi, Kenya. PARTICIPANTS: Twelve baboons with histologically proven spontaneous endometriosis. INTERVENTIONS: Fifty-four serial laparoscopies (4.2 +/- 1.9 per animal, range 1 to 7) were performed after 1 to 3 months (n = 2), 4 to 6 months (n = 1), 7 to 9 months (n = 6), 10 to 12 months (n = 17), 13 to 15 months (n = 7), 16 to 18 months (n = 1), 19 to 21 months (n = 8), 22 to 24 months (n = 8), 25 to 27 months (n = 2), and 30 to 32 months (n = 2). MAIN OUTCOME MEASURE: During each laparoscopy the pelvis was examined for the presence of endometriosis. The number, size, and type of endometriotic implants were noted on a pelvic map and both endometriosis score and stage were calculated. Remodeling was defined as a change in laparoscopic appearance (typical, subtle, suspicious) of an individual endometriotic lesion. Data were analyzed by a signed rank test. RESULTS: Endometriosis was progressive as shown by the significant increase in the number and surface of lesions and in endometriosis scores after 24 months. The total number of endometriotic lesions after 24 months consisted of 69% new (and mostly subtle) implants, 10% remodeled lesions, and 21% unchanged implants. CONCLUSIONS: This study demonstrated that endometriosis in captive baboons undergoing repeated laparoscopies is a dynamic and moderately progressive disease with periods of development and regression and active remodeling between different types of lesions.     

Preliminary report on the effects of propolis on wound healing in the dental pulp

The purpose of this investigation was to determine the antimicrobial and healing potential of propolis on direct dental pulp exposures. This study used 25 adult male rats. Pulp exposures were performed and animals were allocated to propolis and calcium hydroxide (Ca(OH)2 groups. Animals were killed on days 5, 7, 10, and 14. The teeth were routinely processed for histological evaluation. Non-parametric tests were employed to analyze the data. No significant differences were found between study groups on the wound healing of the dental pulp. Both substances were comparable in exhibiting normal reorganization of the pulp and no increased vascularity, and were equally efficacious in maintaining a low inflammatory and microbial cell population as well as in stimulating the formation of reparative dentin.     

Brainstem auditory evoked response development in preterm and term baboons (Papio hamadryas)

Brainstem auditory evoked responses were recorded longitudinally from 11 neonatal baboons (Papio hamadryas), 6 of which were preterm. Recordings were made in unsedated animals from day 161 to day 362 after conception (term = 182 days). The pattern of development of both waveform morphology and of wave latency was consistent with that seen in the human neonate, with a rapid maturation of the response during the perinatal period, and then a slower development to adult values. Brainstem conduction time was measured from the wave I to wave IV interval, and this demonstrated a similar pattern, with a rapid decrease in latency up to term, and then decreasing more slowly to reach adult values by 4 months of age in the baboon.