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1.
The changes in levels of peripheral major lymphocyte subsets were monitored with 10 adult cynomolgus monkeys (5 females and 5 males) during the 9 weeks after immunization with chick type-II collagen in Freund's complete adjuvant. Three females and 3 males developed overt arthritis determined by swelling of small joints and increase of plasma alkaline phosphatase as well as C-reactive protein. An increase of CD16+ NK cells was observed in four non-arthritis-developed monkeys (two females and two males). There was no significant difference in the fluctuation pattern of CD4+ T cell, CD8+ T cell and CD20+ B cell levels between arthritis-developed monkeys and non-developed ones. In addition, the percentages of CD45RA+ CD4+ T cells to total CD4+ T cells, CD28- CD8+ T cells to total CD8+ T cells, and IgD- B cells to total B cells did not significantly differ between them. On the other hand, a significant increase was demonstrated in CD14-positive cells at 3 weeks after immunization in only arthritis-developed monkeys regardless of sex. The expression of CD14 antigen on the surface of increased cells was low in comparison with those appearing in blood obtained before immunization. In addition, increased CD14low cells showed no response to LPS stimulation. However, there was no significant difference in antibody titer to both chick type-II and monkey type-II collagen between arthritis-developed monkeys and non-developed ones. These results suggest that an increase in number of CD14low monocytes with immature function might be a part of the autoimmune response, and that the appearance of these cells is of pathogenic importance in the arthritic process in cynomolgus monkeys regardless of the production of autoantibody.  相似文献   

2.
Shin Nippon Biomedical Laboratories, Ltd. (SNBL) imported and quarantined 3,148 cynomolgus monkeys (aged 2.5 to 6.5 years) from China in 2002. The hematology and blood biochemistry data obtained from these monkeys on Day 32 of quarantine were analyzed separately by sex [2,890 animals in which no abnormalities were observed during the 35-day quarantine period (normal group), and 258 animals which exhibited diarrhea 1 to 12 times (diarrhea group)]. The values obtained for all parameters were within the normal range (mean +/- SD), and no significant abnormalities were noted in either sex. The clinical pathology data from 11 animals (6 males and 5 females) exhibiting diarrhea repeatedly (10 to 12 times) were statistically analyzed, and significant differences were noted in PLT and ALP in both sexes. The PLT values of these animals were within the normal group mean +/- 2 SD, and were considered within the normal range. A significant difference was noted in some individual ALP values (males: Nos. 2 and 3, females: Nos. 1, 3, and 4). The clinical pathology data obtained from the normal group in this study basically correspond to the widely reported results already obtained from healthy cynomolgus monkeys, from which it can be concluded that the cynomolgus monkeys from China were generally healthy and presenting no particular abnormality. The clinical pathology data from the normal group will serve as valuable baseline data for experimenters using cynomolgus monkeys.  相似文献   

3.
Normal hematological values including erythrocyte count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), total leucocyte count (WBC), and differential leucocyte count were determined with 206 healthy cynomolgus monkeys (Macaca fascicularis) aged in 1 to 18 years. These animals were born and reared at Tsukuba Primate Center for Medical Science, NIH, Japan. Additionally, 32 cynomolgus monkeys of wild origin estimated to be 5 or more years old were examined for their hematology. The presence or absence of sex- and age-related differences in the values was statistically analysed. As regards infant and juvenile monkeys, there were no significant differences in RBC, Ht and Hb between males and females. However, these values became significantly larger in males than in females after sexual maturation. Lymphocyte count was larger than neutrophil count until 3 to 4 years of age after birth, but this relation was inverted in adult monkeys aged more than 5 years. Segmentation of the nucleus was a prominent finding in neutrophils. Neither sex- nor age-related difference in the number of nuclear segmentation was noted.  相似文献   

4.
This study investigated fluctuations in hematological values of 50 wild-caught vervet monkeys (African green monkeys, grivets, Chlorocebus aethiops) during habituation to captivity. The monkeys were categorized into four groups according to age and sex viz adult males, adult females, juvenile males, and juvenile females. The erythrocyte values were significantly higher (P<0.05) in the adult males than in the other animals. There was an increase in most of the erythrocyte parameters studied during the monitoring period with the most significant being hemoglobin, hematocrit, and mean corpuscular volume. However, the red cell distribution widths, which were higher in adult females, declined. The total white blood cell (WBC) counts, which were higher in adult females than in the other animals, were closely correlated with granulocytes counts. The WBC levels decreased in all the animals throughout the 8 months study, indicating gradually decreasing stress, but they were relatively stable in males. The platelet counts declined significantly (P<0.05) and at 8 months post capture the counts were higher in females than in males. The juvenile female platelet counts were relatively stable during the monitoring period. The maintenance of the monkeys on an improved stable diet and in environment-controlled housing combined with progressing psycho-physiological adaptation may be important factors for the gradual improvements of the hematological values recorded. There were wide variations in these between individual animals emphasizing the need for long adaptation combined with establishment of individual baseline values before experimental studies.  相似文献   

5.
The effect of differences in sex hormone binding globulin (SHBG) levels associated with reproductive status on free 17 beta-estradiol (E2) and testosterone (T) was characterized in cynomolgus monkeys. Cycling female cynomolgus monkeys had higher SHBG levels than males, pregnant and lactating females (P less than 0.05). Ovariectomized females were not different than control females, suggesting no hypoestrogenic effect. The percentage of free T was elevated in pregnant animals (P less than 0.05) compared to normal males and females, but the percentage of free E2 was similar between these groups. Although a gender difference in the percentages of free E2 and T was not detected, there was a gender difference in the free T and E2 concentrations due to endogenous secretion. Increased free E2 concentrations during pregnancy were the result of endogenous secretion rather than the decreased binding capacity of SHBG; the increased percentage of free T during pregnancy significantly increased free T concentrations. These data suggest that the gender difference in SHBG levels in cynomolgus monkeys is due to androgenic influences and that estrogens have minimal influence. Furthermore, the decrease in SHBG levels during pregnancy and lactation may not be entirely dependent on these androgenic influences.  相似文献   

6.
Iron deficiency anemia is a human health problem of global significance, particularly as it affects pregnant women and infants. While the study of nonhuman primates has resulted in valuable knowledge about iron metabolism, hematologic and biochemical reference ranges for the parameters of iron metabolism are difficult to document in healthy monkeys. At our institution, we maintain a large breeding colony of healthy cynomolgus monkeys (Macaca fascicularis). Data compiled after sampling nonpregnant females and male members of this colony are presented as reference ranges for red cell number, hemoglobin, hematocrit, mean cellular volume, mean cellular hemoglobin, mean cellular hemoglobin concentration, serum iron, total iron-binding capacity, serum transferrin, and serum ferritin.  相似文献   

7.

Background

The cynomolgus monkey (Macaca fascicularis) has been increasingly used in biomedical research, making knowledge of its blood-based parameters essential to support the selection of healthy subjects and its use in preclinical research. As age and sex affect these blood-based parameters, it is important to establish baseline indices for these parameters on an age and sex basis and determine the effects of age and sex on these indices.

Methods

A total of 917 cynomolgus monkeys (374 males and 543 females) were selected and segregated by age (five groups) and sex. A total of 30 hematological and 22 biochemical parameters were measured, and the effects of age and sex were analyzed.

Results

Baseline indices for hematological and biochemical parameters were separately established by age and sex. Significant effects by age, sex, and age-sex interaction were observed in a number of blood parameters. In the 49–60 months and 61–72 months age groups, red blood cell count, hemoglobulin, and hematocrit showed significantly lower values (P<0.01) in females than males. Serum alkaline phosphatase varied with age in both sexes (P<0.01) and was significantly higher in females than males (P<0.05) in the groups aged 13–24 months and 25–36 months; however, in the three groups aged over 25–36 months, serum alkaline phosphatase was significantly lower in females than males (P<0.01). Creatinine concentration increased with age (P<0.01) in all age groups; specifically in the groups aged 49–60 months and 61–72 months, creatinine was significantly higher (P<0.01) in males than females. Total protein and globulin both increased with age (P<0.01).

Conclusion

The baseline values of hematological and biochemical parameters reported herein establish reference indices of blood-based parameters in the cynomolgus monkey by age and sex, thereby aiding researchers in selecting healthy subjects and evaluating preclinical studies using this species.  相似文献   

8.
Selected serum enzymes, cholesterol, triglycerides, glucose, uric acid, protein, albumin, bilirubin, BUN, hematology, and electrocardiograms (EKG) were obtained from adult male cynomolgus (Macaca fascicularis) and adult male stumptailed (Macaca arctoides) macaques. Serum alkaline phosphatase, uric acid, albumin, bilirubin, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and monocytes were significantly lower in the cynomogus monkeys. This relationship was reversed for serum levels of triglycerides, phosphorus, red blood cell counts and lymphocytes. EKG analysis revealed significantly increased PR interval and QRS wave duration in the cynomolgus species. However, there were no differences in heart rate. Right axis deviation was common in both species.  相似文献   

9.
We examined the diurnal variations and the effects of 48-hour fasting on hematological and serum biochemical values to obtain basic physiological data on ten male and seven female G?ttingen minipigs 6 to 16 months of age. For all hematological parameters examined (RBC, HCT, HGB, WBC and PLT), there was no diurnal variation in either sex, but red blood cell parameters were affected by fasting, with an increase in males and a decrease in females. Three serum biochemical parameters (GOT, UN and i.p.) for males and four (GOT, UN, Ca and i.p.) for females exhibited diurnal variation. These variations were eliminated by fasting. The BIL level in males was increased by fasting, and the color of serum was yellowish. Fe concentration in both sexes and CRE and Mg levels in males were decreased by fasting. These findings are basic data for various experiments on minipigs, and indicate that great care is required in establishing feeding times and fasting intervals and in the analysis of results of experiments on minipigs.  相似文献   

10.
As a model for studying methamphetamine (MAP) abuse, which has become a social problem in Japan, we investigated the changes in serum cortisone, NK cell activity and mitogenic response of T-lymphocytes after a single injection of MAP (3.0 mg/kg) in female cynomolgus monkeys. Serum cortisol concentration was significantly elevated to 2.66 times pre-injection levels at 6 h post-injection, and the effect was still observed 24 h later. NK cell activity was significantly elevated at 6 h after MAP injection, but at 24 h after injection had dropped markedly to 49.5% of baseline. Mitogen (PHA) response of lymphocytes was elevated when MAP was injected, and this increased level continued up to 24 h. We speculate that the transient increase in NK cell activity followed by a distinct drop, as well as the changes in T-lymphocytes, may be strongly related to the cortisone concentration.  相似文献   

11.
The standard value of serum insulin was determined to be less than 75 microU/ml with ninety-eight female adult cynomolgus monkeys of wild origin. Then, fifteen apparently healthy laboratory-bred female cynomolgus monkeys aged 6-8 years were studied to know the usefulness of the arginine tolerance test (ATT) by measuring blood glucose, insulin and glucagon. Prior to ATT, all animals had been diagnosed as non-diabetic by the intravenous glucose tolerance test (IVGTT). Arginine hydrochloride was infused intravenously at a dose of 0.5 g/kg. BW under anesthesia. According to the standard value of insulin, fifteen animals were divided into two groups, that is, the low (n = 7) and the high (n = 8) value groups. In the low value group, glucose and insulin value did not change significantly after arginine infusion and their responses were similar to those in the control group (saline infused, n = 4). But glucagon markedly increased from 10 to 45 minutes post infusion. In the high value group, glucagon response was similar to that in the low value group, while glucose and insulin values significantly decreased. It is concluded that the pancreatic alpha-cell function (glucagon secretion) can be judged by the ATT in the cynomolgus monkey but the beta-cell function (insulin secretion) can not be diagnosed.  相似文献   

12.
Abstract: Cross-reactivity between several commercially available mouse antihuman monoclonal antibodies (mAbs), conjugated to phycoerythrin (PE) and fluorescein isothiocyanate (FITC) fluorochromes, and peripheral blood leukocyte surface antigens, has been established in infant cynomolgus (Macaca fascicularis) monkeys using whole blood lysis, and two-color, PE and FITC flow cytometric analysis. With the exception of the CD8 marker, the bivariate dot-plot patterns for all other markers were similar in infant monkeys and in humans. For the CD8 marker, however, a CD8+CD2? population of cells was observed in the majority of monkeys tested (10 out of 12). The number of CD8+CD2? cells was higher (13%) in infant monkeys compared to the 3% reported for adult human blood. The mean percentage and absolute numbers for the cell surface markers identified with the human mAbs CD2 (FITC, Ortho, Paritan, NJ), CD4 (PE, B-D, Mountain View, CA), and CD8 (PE, B-D) when these were combined with a series of PE- or FITC-labelled human mAbs were similar across all combinations tested. Statistically significant differences were observed between male and female monkeys for the mean percentage levels of CD4 (females > males) and for the CD4/CD8 ratio (females > males). Such gender differences need to be taken into consideration when infant cynomolgus monkeys are used as models for chemical-induced immunotoxicity studies. Measurement of the interleukin-2 (IL-2) and transferrin proved to be useful in monitoring in vitro cellular activation in infant cynomolgus and possibly in rhesus (M. mulatta) monkeys.  相似文献   

13.
The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.  相似文献   

14.
We examined hematological parameters for a semifree-ranging population of mandrills to investigate the influence of age and sex, and to establish normative values for age-sex classes. We also investigated the influence of the reproductive cycle on hematological parameters in females and the influence of seasonality on both sexes. We examined hemoglobin concentration, platelet count, white cell count, red cell count, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and differential white cell counts, with a total of 459 observations. Red cell counts, hemoglobin, and hematocrit are significantly lower in females than in males, while female white cell counts are significantly higher. Platelet and white cell counts both decreased with age, while MCV and MCHC (males only) increased with age. Absolute lymphocyte counts also decreased with age. Female reproductive status had little effect on hematology, but melengestrol acetate contraceptive implants resulted in significant increases in hemoglobin, white cell count, red cell count, and hematocrit. Finally, lymphocyte counts increased significantly during the wet season in comparison with dry months, which may be related to increased parasite infection during the wet season. We compare our findings to those for other species, and discuss age-sex patterns in light of mandrill life history. Our results demonstrate the importance of including age-sex class, female reproductive status, and season in studies of hematology and will be useful in further studies of the colony.  相似文献   

15.
Indicators of transport stress were investigated in blood parameters of five male cynomolgus monkeys obtained from abroad. They underwent air and ground travel-related stress in transport cages for a 15-hour transit time. On arrival, hematological parameters of white blood cell count, red blood cell count, hemoglobin concentration, and hematocrit values were within the limits of reference range, indicating that these parameters were not typical changes derived from transport stress loading. An increase in neutrophil-to-lymphocyte (N/L) ratio with a marked increase in neutrophils and a decrease in lymphocytes was observed on arrival, and the increased N/L ratio returned approximately to the normal level 1 week after arrival. The serum cortisol level markedly increased on the day of arrival and it returned to normal 1 week after arrival. These findings indicate that the transport process was stressful for animals, showing increases in N/L ratio as well as cortisol level. Thus, it is possible that an increase in N/L ratio may be utilized as an indirect indicator of transport stress in newly acquired cynomolgus monkeys, as it has the similar pattern of change in cortisol with an increased cortisol level on the day of arrival.  相似文献   

16.

Background

The cynomolgus monkey (Macaca fascicularis) has been increasingly used as a non-human primate model in biomedical research. As establishing baseline thoracic radiography for the cynomolgus monkey is essential, we tested the hypothesis that age and sex may affect the thoracic radiography parameters of this species.

Methods

Here, 697 healthy cynomolgus monkeys were segregated by sex and age (three age groups: 25–36 months, 37–48 months, 49–60 months). The lung length (LL), maximal interior thoracic depth (TD), maximal interior thoracic breadth (TBr), cardiac silhouette breadth (CBr), cardiothoracic ratio (CR), right and left costophrenic angles (RCA and LCA), and right hilar height ratio (R-HHR) were assessed by chest film. Statistical analysis was applied to examine the effect of age, sex, and age × sex interactions.

Results

Significant effects by age were shown for LL, TD, TBr, CBr, and CR. Significant effects by sex were found for TD, TBr, CBr, CR, and R-HHR. Significant effects by age × sex were observed for TD, TBr, CBr, and CR. Both TD and TBr increased with age in both sexes, and both were significantly higher in males than in females in the group aged 49–60 months. CBr increased with age and was significantly higher in males than in females across all age groups. CR declined with age and was significantly higher in males than females across all age groups, and CR was similar or slightly higher relative to those previously found in other non-human primate species. As to the other parameters with no significant sex nor age-related differences, the R-HHR was greater than 1.00, and the angulation of bilateral costophrenic angles were sharp.

Conclusions

The thoracic radiographic parameters for the healthy cynomolgus monkey presented here should prove useful in veterinary practice, research involving non-human primate models of respiratory or cardiovascular disorders, and morphological studies on cynomolgus monkeys.  相似文献   

17.
The aim of the study was to investigate the relationship between liver transaminase levels and metabolic syndrome (MS) features in obese children and adolescents. A total of 132 children and adolescents (73 males and 59 females) aged 8–16, participated in the study. All were studied at the department of Paediatrics, University Hospital of Zaragoza (Spain). Inclusion criteria were the existence of obesity as defined by body mass index (BMI) according to Cole cut-off values (when BMI was higher than the age and sex specific equivalent to 30 kg/m2). The definition of metabolic syndrome was according to the International Diabetes Federation criteria. Weight (kg), height (cm), waist circumference (cm), blood pressure and BMI were measured. Laboratory determinations after overnight fasting included: transaminases (ALT, AST, GGT), fasting glucose, insulin, triglycerides and HDL-C. The MS was found in 21.6% of the obese children and adolescents and the prevalence was higher in males (25.9%) than in females (15.9%). Serum transaminases (ALT, AST and GGT) mean concentrations were higher in males than in females, and decreased during pubertal development. The obese children and adolescents with the MS did not show higher transaminases concentrations when compared with those without the MS. Some MS manifestations (mainly waist circumference) showed a correlation with ALT, although all transaminases values were normal according to adult references. Liver transaminases, a surrogate marker of NAFLD, did not show an early and consistent manifestation of abnormalities in the obese children and adolescents studied. In order to define the presence of the disease, it would be necessary to obtain aminotransferase reference standards for children and adolescents, considering pubertal stage and gender.  相似文献   

18.
Chronic hyperglycemia has been implicated in a number of diabetes mellitus-related conditions in the human population, including retinopathy, neuropathy, nephropathy, and vasculopathy. However, it has been difficult to evaluate the effect of long-term hyperglycemia in a research setting because of the disease's slow progression. In this study, we used streptozotocin (30 mg/kg of body weight, intravenously) to induce a state of chronic hyperglycemia in eight cynomolgus monkeys, and compared these monkeys with a matched control group (n = 8). Seven of eight monkeys with streptozotocin-induced diabetes required insulin therapy to avoid ketosis. After disease induction, all diabetic monkeys had significantly higher preprandial plasma glucose and glycated hemoglobin values, compared with their baseline values or values for control monkeys. Diabetic monkeys also had abnormal responses to an intravenous glucose tolerance test. Consistent with the chronic hyperglycemic state and formation of advanced glycation end products, diabetic monkeys had a significant increase in skin fluorescence over the course of the 6-month study. Plasma triglyceride and cholesterol concentrations increased, but not significantly so, in the diabetic monkeys after disease induction and were not significantly different from concentrations in control monkeys. Six months after disease induction, monkeys were necropsied, and immunohistochemical staining for insulin in the pancreatic islets indicated that diabetic monkeys had a significantly decreased amount of staining for the hormone. The percentage of islet insulin staining was significantly correlated with physiologic responses to the postinduction intravenous glucose tolerance test in all monkeys. Because cynomolgus monkeys are well-characterized models of atherosclerosis, this model may be useful for determining mechanisms whereby diabetes mellitus increases cardiovascular disease.  相似文献   

19.
To assess the changing responsiveness of pituitary gonadotropes to gonadotropin releasing hormone (GnRH) during development, 5 male and 5 female rhesus monkeys were studied. Three monkeys of each sex were tested periodically with a subcutaneous injection of 500 micrograms of GnRH dissolved in 50% polyvinylpyrrolidone (PVP) beginning at 2 to 4 weeks of age and continuing into young adulthood. The remaining 4 monkeys received injections of the vehicle (PVP) alone and served as controls. Serum concentrations of bioactive luteinizing hormone (LH) were determined by an interstitial cell testosterone bioassay, and follicle-stimulating hormone (FSH) levels were measured by radioimmunoassay. Baseline FSH levels in the 5 female neonatal monkeys were higher than those of the 5 male neonatal monkeys during the first 2 months of life. In both sexes, FSH concentrations decreased with age, and FSH was barely detectable by 6 months. Baseline LH values in the 5 female monkeys declined during the first 6 months of the study and were undetectable (less than 0.5 micrograms/ml) at 6 months of age. Baseline LH levels in 4 of the 5 neonatal males also declined to undetectable concentrations by 6 months of age. During the first 3 months of life, there was a striking increase in the serum concentrations of both LH and FSH following GnRH. Although the LH responses to GnRH (delta LH) were similar in males and females of comparable ages, the FSH responses (delta FSH) were considerably greater in the female monkeys. In the males, the delta LH exceeded the delta FSH, whereas in the females, the delta FSH were greater than the delta FSH. In both sexes, the delta LH and delta FSH generally were greatest in the youngest monkeys and decreased gradually with increasing age. By 6 months, the gonadotropin responses to GnRH either were undetectable (males) or very small (females). After 6 months there was no longer an increase in serum gonadotropins after GnRH in either sex until 1.5-4 years (females) or 3 years (males) of age. The delta LH in response to GnRH in the male monkeys 3-5 years of age were comparable to the responses during the first month after birth. Serum concentrations of FSH in the adult males, however, did not increase after GnRH. In the female monkeys, serum levels of LH and FSH increased after GnRH at 1.5 years (1 monkey) and 4 years (2 monkeys) of age. The delta LH were similar to those of the 1- to 2-month-old female monkeys. The delta FSH, however, were variable and were approximately 20% of the neonatal response. In these young adult female monkeys the delta LH exceeded the delta FSH.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

20.
目的研究食蟹猴血液学及血清生化指标日间节律性变化,为正确全面评估血液学及血清生化测定结果提供一定的实验事实依据。方法在9:30(am)~10:30(am)、12:30(pm)~13:30(pm)、15:30(pm)~16:30(pm)及19:30(pm)~20:30(pm)4个时间段对12只食蟹猴(雌雄各半)采血。采用全自动血细胞分析仪及血液生化分析仪分别测定血液学及血清生化指标。利用高效液相色谱(HPLC)方法分析血浆中皮质醇含量。结果雌雄食蟹猴下午白细胞数(WBC)及尿素氮(BUN)显著升高;雌性食蟹猴下午血红蛋白(HGB)及血细胞压积(HCT)显著降低,天门冬氨酸氨基转换酶(AST)及丙氨酸氨基转换酶(ALT)活性显著升高;雄性食蟹猴下午血糖(GLU)及血浆皮质醇显著降低。结论雌雄食蟹猴血液学及血清生化部分指标存在明显的日间节律性。  相似文献   

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