Ligature-induced marginal inflammation around osseointegrated implants and ankylosed teeth: stereologic and histologic observations in cynomolgus monkeys (Macaca fascicularis)

The aim of the investigation was to provide quantitative and qualitative histologic data on marginal inflammation around osseointegrated implants. The significance of the lack of a periodontal ligament in the initial breakdown phase of supporting tissues in implants was examined by comparing stereologic and histologic manifestations of ligature-induced marginal inflammation around osseointegrated implants with those around ankylosed and normal control teeth in 8 cynomolgus monkeys (Macaca fascicularis). Clinical and radiographic findings have been reported elsewhere. The marginal connective tissue around ligated implants was infiltrated by a significantly increased total number of lymphocytes, plasma cells, and neutrophils compared to non-ligated implants and teeth. The total number of lymphocytes around ligated implants was significantly higher than around ligated ankylosed and normal control teeth. There were, however, no significant differences in the total number of plasma cells and neutrophils within the ligated group. Osteoclasts were exclusively observed around ligated implants and ankylosed teeth. Although variations in microbiota and susceptibility of different jaw positions to periodontal break-down may influence the results of the present study, the results seem to substantiate the theory that marginal inflammation around implants and ankylosed teeth may have more serious implications than does marginal inflammation around teeth with a periodontal ligament. Since presence of osteoclasts was not related to the absence of cervical cementum with inserting gingival fibers around ligated ankylosed teeth, the increased susceptibility of bone loss of implants is probably not caused by the absence of these tissue components. In contrast, the histologic observations seem to support that the increased susceptibility for bone loss around implants may be related to the absence of a periodontal ligament.     

Cyclic changes in genital organs and vaginal cytology in cynomolgus monkeys (Macaca fascicularis)

Vaginal cytology was evaluated weekly over 12 months in 20 adult female Cynomolgus monkeys (Macaca fascicularis). After sacrifice of the animals the histology of the ovaries, uterus and vagina were studied in different phases of the menstrual cycle. The cytological examination of the vaginal smears showed that the superficial cells increased in number towards the middle of the cycle and the number of intermediate cells declined gradually. Parabasal cells were observed mainly at the beginning of the cycle; they disappeared towards the middle of the menstrual cycle. During the early follicular phase, the cells were moderately separated from each other, and during the second half of the proliferative or follicular phase, the superficial cells appeared clumped together. Leucocytes were usually absent except for at the beginning of the cycle and in the last few days of the late secretory or luteal phase. The maturation index of the vaginal smears can be considered as a tool for distinguishing the different phases of the menstrual cycle. The microscopic examination of the genital organs showed that during the proliferative or follicular phase of the cycle, which corresponds to the development of the ovarian follicles, the uterus showed growth of endometrial glands, stroma and endothelial cell proliferation with capillary sprouts. Shortly after ovulation and parallel to the formation of the corpora lutea, the endometrium enters the secretory or luteal phase, which is characterized by coiling of endometrial glands, glandular secretion and the differentiation of the spiral artery. The most striking changes in the vagina, is the marked basal cell proliferation and thickening of the stratum granulosum during the follicular phase of the menstrual cycle. The histological changes observed in the vagina demonstrated a good correlation with the observation on cytological examination of the smears. The present study demonstrated that the process of angiogenesis in the uterus during the different phases of the menstrual cycle is a multiple phenomenon involving proliferation, maturation and differentiation.     

Fatal disseminated cercopithecine herpesvirus 1 (herpes B infection in cynomolgus monkeys (Macaca fascicularis)

Two adult female cynomolgus monkeys (Macaca fascicularis) that had been housed together for 4 months died within 2 weeks of each other after brief illnesses. Monkey No. 1 presented with collapse, watery stool, and hypothermia and died overnight. Monkey No. 2 presented with dyspnea, nasal discharge, leukopenia, and hypoproteinemia and was euthanized after 2 days. Both animals had peritoneal effusions, massive necrosis of pharyngeal, esophageal, and gastric mucosa, and multifocal hepatic and pancreatic necrosis. Monkey No. 2 also had lingual ulcers and locally extensive necrosis of spleen, adrenal glands, and lymph nodes. Large numbers of eosinophilic intranuclear inclusion bodies were present in epithelial and syncytial cells adjoining the necrotic foci in Monkey No. 2 but were absent in Monkey No. 1. Monkey No. 1 seroconverted to cercopithecine herpesvirus 1 (CHV-1, commonly known as herpes B) in the month before death. CHV-1 was isolated from a sample of stomach from Monkey No. 2, and electron microscopy of liver from this animal demonstrated herpesvirus particles within hepatocytes. Both animals were seropositive for simian type D retrovirus, and the virus was cultured from the liver of Monkey No. 2. A diagnosis of disseminated CHV-1 infection was made, possibly occurring secondary to immunosuppression due to infection with simian type D retrovirus. Although a high percentage of cynomolgus monkeys are apparently infected with CHV-1, disseminated disease is rare. Because infection with CHV-1 in humans is associated with a high fatality rate, familiarity with the lesions of disseminated infection with this virus is important.     

Failure of carbon monoxide to induce myocardial infarction in cholesterol-fed cynomolgus monkeys (Macaca fascicularis)

The effect of prenatal administration of different doses of cortisone, corticosterone, dexamethasone, triamcinolone and prednisolone on the fetus and its palatal development was studied. All the glucocorticoids, except cortisone, produced cleft palate in the fetuses. Both the total frequency and morphologically different types of cleft palate were related to the dose of the teratogen. Triamcinolone appeared to be more potent than other glucocorticoid in inducing cleft palate. An association was noted between fetal growth inhibition, the dose of the teratogen and the frequency and type of cleft palate.     

Reproducibility of automated periodontal probing around teeth and osseointegrated oral implants

The Trk family, a group of high-affinity neurotrophin receptors, is divided into three subtypes, TrkA, TrkB and TrkC. These were originally found in neural elements, and are involved in neural development, maintenance and survival. Recent studies have shown that non-neural cells in vitro also express mRNA encoding some neurotrophin receptors. In our preliminary study, TrkB-like immunoreactivity (LI) was found in the various non-neural cells in the rat periodontal ligament. The present study was undertaken to clarify which cell types express Trk-LI, in particular two types of TrkB-LI, in the periodontal ligament of mature rats, using an immunocytochemical technique with polyclonal antibodies. Intense full-length TrkB-LI was clearly recognized in non-neural cells such as fibroblasts, osteoclasts, odontoclasts and cementoblasts as well as in neural elements. Relatively large cells with many cytoplasmic processes were also frequently immunopositive for full-length TrkB. Immunocytochemistry for TrkB[TK-], a truncated type, also demonstrated a similar immunostaining pattern to that of full-length TrkB in non-neural periodontal cells, and intense positive reactions in endothelial cells. Some non-neural cells were positive for TrkA and TrkC. These findings suggest that neurotrophic factors, the ligands of the Trk family, have certain effects on the proliferation and/or differentiation of non-neural cells, as well as on their neurotrophic functions.     

Experimental hepatitis E: pathogenesis in cynomolgus macaques (Macaca fascicularis)

Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6-mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty-eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P < or = .001), white blood cell count less than 5,000/microL at relapse (P = .036) and duration of first remission greater than 54 months (P = .039) were independently associated with a more favorable outcome. While the randomized trial was inconclusive, prolonged second complete remissions were secured in more than one-third of children with a late BM relapse of ALL. The prognostic factors identified may help select children with a late BM relapse who can be successfully retreated with chemotherapy alone.     

Use of peripheral quantitative computed tomography for densitometry of the femoral neck and spine in cynomolgus monkeys (Macaca fascicularis)

BACKGROUND AND METHODS: Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. RESULTS: The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake. CONCLUSIONS: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.     

Characterization of CYP1A in hepatocytes of cynomolgus monkeys (Macaca fascicularis) and induction by different substituted polychlorinated biphenyls (PCBs)

We have developed a mathematical algorithm to compare and distinguish matrix-assisted laser desorption/ionization (MALDI) mass spectra of whole bacteria cells. This fingerprint matching technique eliminates the subjectivity involved in visually comparing two spectra to determine whether they match and it provides a quantitative measure of spectral similarity. Using it, we have distinguished twenty five different strains of a single bacteria species, E. coli. Cells are grown in culture, samples are prepared, and MALDI-TOF mass spectra are recorded for each strain. Pairs of spectra are compared by a modified cross-correlation procedure. This modified approach increases the sensitivity of correlation analysis to small spectral differences. The technique can be fine-tuned by varying the number of intervals into which spectra are divided.     

The weight of the reproductive organs, hypophysis and thyroid of male cynomolgus monkeys. (Macaca fascicularis) (author's transl)

The present short paper deals with the weight of the male reproductive organs of wild-imported cynomolgus monkeys, including the testes, epididymides, ductus deferens, vesicula seminalis prostata, bulbo urethralis and penis. In addition, the size of the testes and the weight of the thyroid and hypophysis are also presented.     

A study of caloric restriction and cardiovascular aging in cynomolgus monkeys (Macaca fascicularis): a potential model for aging research

Caloric restriction has been demonstrated to retard aging processes and extend maximal life span in rodents, and is currently being evaluated in several nonhuman primate trials. We initiated a study in 32 adult cynomolgus monkeys to evaluate the effect of caloric restriction on parameters contributing to atherosclerosis extent. Following pretrial determinations, at which time a baseline measure of ad libitum (ad lib) dietary intake was assessed, animals were randomized to an ad lib fed group (control) or a caloric restriction group (30% reduction from baseline intake). The animals are being evaluated for glycated proteins, insulin, glucose, insulin sensitivity measures, and specific measures of body fat composition by CT scans (e.g., intra-abdominal fat) over specified intervals. The results from the first year of observation demonstrate a significant diet effect on body weight, and specifically intra-abdominal fat. Further, insulin sensitivity has been significantly increased after 1 year of caloric restriction compared to the ad lib fed group. These studies indicate that caloric restriction has a marked effect on a pathologic fat depot, and this change is associated significantly with an improvement in peripheral tissue insulin sensitivity.     

Effects of the nonsteroidal aromatase inhibitor, fadrozole, on the sexual behavior of male cynomolgus monkeys (Macaca fascicularis)

In many vertebrates, castration and hormone replacement and, more recently, the use of aromatase inhibitors, have shown that male sexual activity is mediated by the aromatization of testosterone (T) to estradiol (E2). In macaques, however, the systemic administration of E2, either alone or in combination with androgen, failed either to maintain or to restore the sexual activity of castrated males. The present study examines the effects of administering the nonsteroidal aromatase inhibitor, Fadrozole, either alone or combined with E2, to castrated, T-treated male cynomolgus monkeys at a dose of 0.25 mg/kg/day. This dose inhibited by over 98% the conversion of T to E2 and the subsequent accumulation of the latter in hypothalamic cell nuclei. Castrated males bearing sc Silastic impants of T were each tested with an ovariectomized, E2-treated female partner before, during, and after being given minipumps delivering either Fadrozole or water (240 1-hr tests). Within 2 weeks, Fadrozole significantly reduced ejaculatory activity and male sexual motivation in the absence of changes in plasma T levels, which remained in the upper range for intact males. Additional estradiol treatment produced small but significant increases in ejaculations by three of the six males only, and measures of male sexual motivation remained unchanged (120 tests). The present results, which stand in contrast to our previous findings in macaques, support the view that aromatization of T is important for ejaculatory activity and sexual motivation in a male primate. They also suggest that exogenous E2, which reaches the brain from the systemic circulation, does not fully duplicate the behavioral effects of E2 produced locally in the brain by the aromatization of T.     

Comparison of two methods of assisted fertilization in cynomolgus monkeys (Macaca fascicularis): intracytoplasmic sperm injection and partial zona dissection followed by insemination

Intracytoplasmic sperm injection (ICSI) and partial zona dissection followed by insemination (PZD-I) were used to establish a microinjection system in cynomolgus monkeys (Macaca fascicularis), which are potential models for human reproduction. Two experimental systems were studied, in which either hamster oocytes or cynomolgus monkey oocytes were used as the vehicle. When hamster oocytes were used, 66 out of 81 ICSI-treated oocytes (82%) showed sperm head swelling or pronucleus formation. Following PZD-I of hamster oocytes the rates of spermatozoa penetration (85/114; 75%) and fertilization (71/114; 62%) were relatively high. When cynomolgus monkey oocytes were used, 19 out of 31 (61%) were fertilized by ICSI with cynomolgus monkey spermatozoa and, subsequently, two embryos (7%) developed to the morula stage. In total, 94% (15/16) of the PZD-I treated oocytes were penetrated by spermatozoa and 63% (10/16) were fertilized. These results demonstrate that both micromanipulation techniques can be used in assisted fertilization with cynomolgus monkeys.     

Developmental toxicity of fleroxacin and comparative pharmacokinetics of four fluoroquinolones in the cynomolgus macaque (Macaca fascicularis)

The potential developmental toxicity of fleroxacin was studied (Phase I) and its pharmacokinetics was compared to ciprofloxacin, temafloxacin, and norfloxacin (Phase II) in the cynomolgus macaque (Macaca fascicularis). Phase I studies involved oral administration of fleroxacin (35 and 70 mg/kg-day) during Gestational Days (GD) 20-34 or 35-49 (N = 10/group); controls received vehicle only. Increased maternal toxicity (weight loss, anorexia, emesis) and embryolethality (4/10, 40%; GD 20-34) were observed at 70 mg/kg-day. Urinary excretion of estrogen conjugates was reduced for females with nonviable pregnancies during both treatment periods (GD 20-34 and 35-49), although steroid hormone levels in serum remained unchanged during treatment; no malformations or growth retardation were observed at gross examination. For Phase II studies, the pharmacokinetics of fleroxacin (70 mg/kg), ciprofloxacin (100 mg/kg), temafloxacin (100 mg/kg), and norfloxacin (150 mg/kg) were studied during a 3-day oral treatment regimen in the nonpregnant (N = 12; 3/quinolone) and pregnant (N = 3; fleroxacin only) macaque. Serial blood samples were collected on the first and third days of treatment in all animals; for pregnant females, the conceptus was removed on GD 31 for analysis of fleroxacin levels. Marked differences between the quinolones were noted in the AUC0-24 hr for nonpregnant females. Based on AUC0-24 hr on the first day of treatment, the rank order was fleroxacin > temafloxacin > ciprofloxacin > norfloxacin. On the third of treatment, the rank order for exposure was temafloxacin > fleroxacin > ciprofloxacin > norfloxacin. Overall, results indicated (1) no marked differences in pharmacokinetic parameters in pregnant versus nonpregnant females, (2) fleroxacin levels in embryonic tissues were similar to maternal plasma levels, and (3) there was a correlation between exposure and embryolethal doses for all fluoroquinolones which resulted in embryolethality except norfloxacin.     

Resistance to psychopathology in adolescent monkeys (Macaca fascicularis) reared with mothers and peers.

Extended S. J. Suomi's (1971) incarceration-separation procedure for the production of depressive behavior pathology to mother- and peer-reared, adolescent Java monkeys (2 males and 2 females) (Macaca fascicularis). In light of recent protein deprivation studies, an attempt to assess the extent of self-inflicted food deprivation was also made. Although there were significant differences in the amount of food consumed, no pathological behavior patterns developed. In general, the experimental manipulations appeared to be associated with increased social interest rather than with depression. Mother-peer-reared adolescents appear to be resistant to experimentally induced psychopathology. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association between marginal bone loss around osseointegrated mandibular implants and smoking habits: a 10-year follow-up study

While many factors are conceivable, occlusal loading and plaque-induced inflammation are frequently stated as the most important ones negatively affecting the prognosis of oral implants. Currently, little is known about the relative importance of such factors. The aim of this study was to analyze the influence of smoking and other possibly relevant factors on bone loss around mandibular implants. The participants were 45 edentulous patients, 21 smokers and 24 non-smokers, who were followed for 10-year period after treatment with a fixed implant-supported prosthesis in the mandible. The peri-implant bone level was measured on intraoral radiographs, information about smoking habits was based on a careful interview, and oral hygiene was evaluated from clinical registration of plaque accumulation. Besides standard statistical methods, multiple linear regression models were constructed for estimation of the relative influence of some factors on peri-implant bone loss. The long-term results of the implant treatment were good, and only three implants (1%) were lost. The mean marginal bone loss around the mandibular implants was very small, about 1 mm for the entire 10-year period. It was greater in smokers than in non-smokers and correlated to the amount of cigarette consumption. Smokers with poor oral hygiene showed greater marginal bone loss around the mandibular implants than those with good oral hygiene. Oral hygiene did not significantly affect bone loss in non-smokers. Multivariate analyses showed that smoking was the most important factor among those analyzed for association with peri-implant bone loss. The separate models for smokers and non-smokers revealed that oral hygiene had a greater impact on peri-implant bone loss among smokers than among non-smokers. This study showed that smoking was the most important factor affecting the rate of peri-implant bone loss, and that oral hygiene also had an influence, especially in smokers, while other factors, e.g., those associated with occlusal loading, were of minor importance. These results indicate that smoking habits should be included in analyses of implant survival and peri-implant bone loss.     

Aging, dominance history, and social behavior in Java-monkeys (Macaca fascicularis)

The aim of this study was to investigate the influence of the dominance history of socially housed Java-monkeys on the aging process. In monkeys, social subordinance is generally associated with elevated levels of cortisol, which, in turn, have been suggested to influence cognitive decline. As cognitive skills are necessary for successful social life, we investigated the effect of old age in relation to the dominance history of the animals on their social behavior by comparing old females with their younger daughters. Old age, especially in combination with a history of low rank, led to a withdrawal from social interactions with unfamiliar animals and to a decrease in amounts of aggression received. Still, however, old animals showed an increase in behaviors associated with arousal. A reduced ability to deal with complex social interactions, caused by a decline in information processing abilities, is suggested as an explanation for these results.     

Evaluation of consecutively placed unloaded root-form and plate-form implants in adult Macaca mulatta monkeys

The present paper describes 18 consecutively-treated non-human primates (Macaca mulatta) as part of a balanced block design study of 36 animals to examine osseointegration in root- and plate-form implants prepared by atraumatic preparation of bone. Clinical measurements around selected teeth and digital radiology were utilized to monitor periodontal disease and bone deposition around the unloaded implants. Once a month scaling procedures were utilized as a means of preventing further advance of periodontal disease. Results indicate that once-monthly regimen of scaling and root planing can prevent attachment loss of natural teeth and will not interfere with the healing of either type of implant; once-monthly scalings produce significant reduction in redness (P < .05) and reduced probing depths (P = .01). A second finding is that both root and blade implants show radiographic evidence of osseointegration in this primate model. The quantitative analysis demonstrates bone gain is not stabilized until 6 months after healing. The data may indicate that occlusal loading of mandibular implants at 3 months may be premature.     

Hormonal regulation and germ cell-specific expression of heat shock protein 60 (hsp60) in the testis of macaque monkeys (Macaca mulatta and M. fascicularis)

FNA smears from six histologically documented cases of tubular adenoma of breast were critically analysed and compared with 10 histologically confirmed cases of fibroadenoma (five pericanalicular and five intracanalicular). Initially a cytological diagnosis of tubular adenoma was rendered only in one case. On review, two cases could be characterized as tubular adenoma, while the findings were suggestive in two others. The features helpful in diagnosis of tubular adenoma were the presence of benign ductal cells as three-dimensional cohesive balls and tubular structures in highly cellular smears. Stroma was conspicuously scanty or absent. Myoepithelial cells were present along with sheets of ductal cells as well as bipolar naked nuclei. Confusion with fibroadenoma occurred in two cases due to presence of a stag-horn pattern of ductal cells.     

Sonographic heat generation in vivo in the gravid long-tailed macaque (Macaca fascicularis)

Temperature elevations that occur during diagnostic ultrasonic exposure were assessed in vivo in gravid macaques after 10, 20, or 30 min (scan mode; N = 30) or 5, 10, or 15 min (pulsed Doppler; N = 32). Five time points were assessed during the second and third trimesters (gestational days 70 to 150 +/- 2; term, approximately 165 days) using a transient thermocouple technique. Measurements were obtained intracranially or at the muscle-bone interface using a commercial sector scanner (ATL MK 600, 7.5 MHz scanhead; scan mode, ISPTA) = 27 mW/cm2, ISPPA = 85 W/cm2, pulse repetition frequency (PRF) = 1 kHz; pulsed Doppler - ISPTA = 54 mW/cm2, ISPPA = 1.5 W/cm2, PRF = 18.5 kHz). Overall, the greatest temperature elevation achieved with either modality or location was 0.6 degrees C.     

Load transmission in implant superstructures supported by natural teeth and osseointegrated dental implants. A preliminary report

There is considerable debate as to the effects of using bridges which are supported simultaneously by teeth and implants, due to the marked differences in their displaceability. This in-vivo experiment was carried out on three subjects, and measured the vertical and horizontal movement of implants and teeth, linked with a fixed superstructure, when this was loaded. The results suggest that natural abutment teeth may contribute significantly to bridge support in these circumstances.