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Objective:To evaluate the residual stepping ability in monkeys with spinal cord injury longitudinally. Methods:Four adult female monkeys were studied. Right hemisection of 10 mm spinal cord tissue was performed at the T7-9 segment. Gait tests of bipedal locomotion were performed before, and six weeks and twelve weeks after injury by VICON system. Gait cycle duration, amplitude of knee and ankle angles, and ratio of united parameters were obtained from successive stepping and were quantitative analyzed. Results:The coordination of bilateral hindlimbs was destroyed after spinal cord injury, and the right hindlimb showed obviously dragging. The gait cycle duration of the left hindlimb increased significantly (P < 0.001), and the amplitudes of knee and ankle angle significantly increased (P < 0.001) after spinal cord injury. The ratio of united parameters was not statistically different among all the time points (P > 0.05). The gait cycle duration of the left hindlimb was correlated with step length (r = 0.838, P = 0.001), step height (r = 0.726, P = 0.007) and amplitude of ankle angle (r = 0.766, P = 0.004), and the amplitude of ankle angle was correlated with step length (r = 0.627, P = 0.029). Conclusion:The gait pattern of monkey with spinal cord injury has been changed. The gait strategy of the uninjured side was adjusted compensatively after spinal cord injury to adapt the functional impairment of contralateral hindlimb.
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Objective To examine the nonhuman primate(NHP)model of acute cerebral infarction thrombus-thrombolysis using multi-parameter high-field magnetic resonance imaging(MRI). Methods Altogether, 8 adult male rhesus monkeys aged 8.2(± 1.2)years old and weighing 9.4(± 1.0)kg were randomized into an infarction group(n=4)and thrombolysis group(n =4). Middle cerebral artery occlusion(MCAO)was induced with a clot in the M1 segment. Monkeys in the thrombolysis group were treated with the recombinant tissue plasminogen activator, rt-PA, while those in the infarction group were treated with 0.9% NaCl only. T2 weighted imaging(T2WI), T2-weighted-fluid-attenuated inversion recovery(T2-FLAIR), time-of-flight magnetic resonance angiography(TOF-MRA), and diffusion-weighted imaging(DWI)were used to examine all monkeys at 4 and 24 h after onset of ischemia. Results The rhesus monkey thrombus-thrombolysis model was successfully established. MRA showed that the middle cerebral artery(MCA) was not recanalized in the infarction group, but was recanalized in the thrombolysis group. T2WI sequence showed an increase in infarction volume(12 027 ± 5507 mm3)in the infarction group compared with the thrombolysis group(4910 ± 2764 mm3). DWI sequence showed an increase in infarction volume(9498 ± 5226 mm3)in the infarction group and thrombolysis group(4854 ± 1792 mm3). Both T2WI and DWI sequences showed no significant difference in infarction volume at 4 h between the two groups, while infarction volume in the thrombolysis group at 24 h was significantly lower compared with the infarction group. The increase in infarction volume was significantly lower in the thrombolysis group compared with the infarction group. Conclusions MRI sequences can be used to successfully evaluate recanalization and infarct changes in the thrombus-thrombolysis model in rhesus monkeys.
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Objective To establish a safe and effective method of rhesus monkey biopsy to take liver and kidney samples under B-mode ultrasound guidance. Methods A total of 4 adult monkeys(weight:8-12 kg; sex: male; age:11 -12 years old)were anaesthetized with 5 -10 mg/kg of ketamine hydrochloride for each through intramuscular injection. After successful anesthesia, abdominal shaving and iodophor disinfection, they were monitored from intercostal area of right upper quadrant or lateral waist subcostal abdomen portions to find liver or kidney organ by MyLab 30CV B-mode ultrasonography with 3.5 Hz transducer which was fixed with a guiding frame. Large vessels such as the portal vein and inferior vena cava were carefully avoided. The range of the biopsy gun was set to 15 mm. When the puncture target and the puncture needle were positioned in the guide line, the puncture target was perpendicular to the puncture needle, and then the trigger button of the puncture needle was pressed to obtain the liver or kidney tissue samples respectively. After puncture,the needle was pulled out quickly. The obtained liver and kidney tissues were used to extract RNA. Results About 13 mg of liver or kidney tissue was obtained by each puncture with volume convertion. This method was fast,reliable and safe,and the total RNA had high purity and integrity. There was no postoperative bleeding and infection. Conclusions This is a very important method for obtaining liver and kidney tissue samples of rhesus monkeys with the guidance of ultrasound. With this method, the research cost can be reduced, the life quality and animal welfare of laboratory non-human primates can be improved,and the accuracy of experimental result can be ensured.
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Objective To observe the changes of circadian characteristics and stress-response-related physiological parameters including respiration, blood pressure, electrocardiography and body temperature of conscious rhesus monkeys by implantable telemetry technique. Methods Surgery was performed on 8 rhesus monkeys (half male and half female, 3-5 years old) for implantation of a telemetry transmitter. After 3 weeks of recovery, the physiological parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus monkeys without binding were automatically recorded by a DSI telemetry system and the data were analyzed by the Ponemah software. Results Some electrocardiographic indexes showed significant differences at daytime and nighttime (P＜ 0. 05 or P＜ 0. 01) including mean heart rate (HR) ( 155. 0-122. 4 times/min), respiratory rate interval (RR-I) (410. 8-535. 7 ms), T-wave amplitude (T-A) (0. 181-0. 157 mV), PR interval (PR-I) (80. 4-87. 4 ms), QT interval (QT-I) (224. 8-263. 9 ms), and corrected QTcb interval (QTcb) (352. 3-366. 7 ms). The indexes of blood pressure and respiration at daytime were significantly higher than those at nighttime (P＜ 0. 01), including the mean systolic pressure (SYS) at daytime and nighttime (144. 6-131. 6 mmHg), diastolic pressure (DIA) (99. 8- 89. 9 mmHg), mean arterial pressure (MAP) (121. 5-110. 2 mmHg), tidal volume (TV) (64. 5-36. 6 mL), minute ventilation (MV) (1931. 9-920. 1 mL/min), and respiratory rate (RR) (32. 3-25. 4 times/min). Cleaning and feeding activities of the laboratory staff at 9: 00 a.m. and 2: 00 p.m. had a certain effect on the stress-responses in the monkeys. Conclusions The parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus macaques observed by implanted telemetry system show obvious circadian changes, which can truly reflect the changes of physiological indexes at daytime and nighttime, and avoid the stress in hungry monkeys caused by the feeding and cleaning activities of laboratory staff. This technique can improve the efficiency of drug safety pharmacology studies, reduce the number of animals used and meet the requirements of 3R principles.
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@#Objective To observe the influence of spinal cord injury on lower limbs weight support capacity,and the changes with time. Methods Six adult female rhesus monkeys with thoracic(T7-9)right spinal cord hemi-section were measured the plantar pressure ratio of both lower limbs with Foot-Scan system before,and six and twelve weeks after operation. Results There was no statistical difference between both sides of limbs before operation(Z=-1.330,P>0.05),while the plantar pressure ratio was more on the left limbs six and twelve weeks after operation(Z>4.783,P<0.001).The plantar pressure ratio of right lower limb became less and less during observation(Z=3.191,P<0.001). Conclusion The weight support capacity of affected limbs is injured after spinal cord hemi-section in monkeys, and would become worse without intervention.
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Objective To provide a simple, convenient, and safe anesthesia method for the establishment of a M1 segment of middle cerebral artery occlusion model in rhesus monkey or other large laboratory animals.Method Twenty male rhesus monkeys weighing 7-11 kg (ages 7-9 years) from Academy of Military Medical Sciences were used in this study.Sumianxin injection combined with 0.1 mg/kg ketamine was given before endotracheal intubation (ID:4.5-5.5#).The animals were then transported to an interventional operation room, where the intravenous access was established and a urinary catheter was inserted into the urinary bladder.Mechanical ventilation was used during the surgery, propofol was continuously injected in a speed of 2-4 mg/kg/h, and Sumianxin-ketamine could be given if necessary to maintain adequate anesthesia depth.The dose was adjusted according to vital signs of the rhesus such as body movements, physiological parameters, and demand of surgery.Brain MRI examination was performed before and after thrombolysis.Anesthetic injection was suspended and the animals were allowed to have a spontaneous breathing every time before the MRI text.Heart rates, temperature, non-invasive blood pressure, and SpO2 were monitored during the whole surgery.Blood samples were taken from the radial artery for blood gas analysis after anesthesia induction and during operation.Results All the 20 animals underwent the operation successfully, no animal had restlessness, respiratory depression, arrhythmia and other serious complications.At the end of the study, animals awake soon.Fifteen of them survived longer than 24 hours, only 5 died from serious cerebral hemorrhage and larger cerebral infarction.Conclusions General endotracheal anesthesia is safe for rhesus monkeys during such interventional operation and MRI examination.
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Objective@#To analyze the prevalence, genetic structure and evolutionary characteristics of GⅡ.17 norovirus isolated from the fecal samples of rhesus monkeys in Longhu Mountain of Guangxi Zhuang Autonomous Region.@*Methods@#A total of 400 stool specimens were collected from wild rhesus monkeys from March to August of 2015. The GⅡ.17 norovirus named as GX213 was identified in fecal samples by high-throughput sequencing technology. Reverse transcription-polymerase chain reaction was used to confirm and screen GX213, as well as amplify its complete gene sequence. Then the sequence and phylogenetic analysis of three ORFs of GX213 were constructed by software MEGA 6.0.@*Results@#Two out of 400 fecal samples were positive. The full-length genome of GX213 was 7 565 bp (containing PloyA tail), which was composed of three open reading frames (ORFs): ORF1(10-5112 nt), ORF2(5093-6715 nt)and ORF3(6715-7494 nt), with 20 bp overlapping between ORF1 and ORF2, and 1 bp overlapping between ORF2 and ORF3.Analysis of the complete sequence of GX213 showed that it shared the highest homology with the strain of human GⅡ.17 norovirus CUHK-NS-613 (GenBank ID: KU561248) (99.5% identity), and ORF1 and ORF3 also shared the highest homology with the strain CUHK-NS-613 [99.5% and 99.4% in nucleotide (nt); 99.5% and 99.2% in amino acid (aa), respectively], which was the main cause of human norovirus outbreaks in some regions of Asia from 2014 to 2015. ORF2 sequence analysis showed that it displayed the highest identity (99.4% in nt and 99.8% in aa) to the strain CUHK-NS-491 (GenBank ID: KP698928), only one aa mutation aa245P→S(P1.1 region) was observed in the GX213 VP1 protein. Furthermore, the phylogenetic analysis showed that GX213 was more related to CUHK-NS-613 and CUHK-NS-491 than the strain KM1509 (GenBank ID: KX356908) of GⅡ.17 norovirus recently identified in rhesus monkeys.@*Conclusions@#GX213 belongs to the human GⅡ.17 norovirus variant causing the norovirus outbreaks from 2014 to 2015. Our research suggests that GⅡ.17 norovirus can infect not only humans but also rhesus monkeys.
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The present study was designed to characterize the blood chemistry, hematology, and lymphocyte subsets in pregnant rhesus monkeys and provide baseline parameters for future studies of reproductive and developmental toxicity and developmental immunotoxicity. Harem-mating was used in 96 female and 16 male rhesus monkeys. Pregnancy was confirmed on gestation day (GD)18 by ultrasound. The blood samples of rhesus monkeys were collected at various times (20 days before pregnancy and GD20, 100 and 150). The analyses of blood chemistry, hematology, and lymphocyte subsets were performed. Compared with 20 days before pregnancy, Significant decreases (P < 0.05) were observed in HCT and RBC on GD20, GD150 and in HGB on GD150, Significant increases in NEUT and decreases in LYMPH on GD20 were observed. Significant decreases in ALB from GD20 to GD150 were observed, significant decreases in TP was observed on GD100. Significant increases in mean GLU were observed on GD20 and GD150 during pregnancy. Significant decreases (P < 0.05) in CD20(+) subsets on GD100, GD150 and CD4(+)/CD8(+)ratio on GD150 were observed, The significant changes of MCV, MCHC, RDW-SD, MCV, MONO, ALT, AST, GLB, ALP, TBIL, DBIL, IBIL, GGT, CR-S, URIC, TC, TG and CK were observed during the pregnant period, but no biologic change were observed, There were no significant changes in MCH, RDW-CV, MPV, BUN, CD3(+), CD4(+) and CD8(+) during pregnancy. These data provide a database for preclinical study in rhesus monkeys. Physiological anemia, hyperglycemia, and immune suppression may occur in pregnant rhesus monkey which is similar to that found in human, and it is essential to distinguish the physiological changes from the pharmacological effects in reproductive and developmental toxicity and developmental immunotoxicity studies of pharmaceuticals.
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Animals , Female , Humans , Male , Pregnancy , Blood Chemical Analysis , Hematology , Lymphocyte Subsets , Allergy and Immunology , Macaca mulatta , Blood , Allergy and Immunology , Models, Animal , Blood , Allergy and Immunology , ReproductionABSTRACT
Objective To understand the characteristics and rules of behavior and preliminary study on the change of psychological state and behavior of infant rhesus monkeys after weaning by artificial feed .Methods 290 infant rhesus monkeys were born in 2012, individual behavior of infant rhesus monkeys were observed and recorded by the methods of ad libitum sampling and chronography .Results The behavior of huddling , sucking finger and sucking body of companion were observed in the first month , the behavior of huddling and sucking finger were significantly increased in the second and third month(P <0.05), sucking body of companion in second month were significantly higher than the first month (P <0.05);the new behavior pacing , sucking genitalia and mounting were observed in the second month , pacing and sucking were significantly increased in the third month ( P <0.05 ) , mounting did not have obvious change; in the third month , sucking toe behavior ware recorded and did not change with time; The proportion of huddling behavior occurred between female and female was significantly higher than opposite sex or male in the same cage .The male infant monkeys were more likely to occurred pacing behavior than female .Sucking body of companion and sucking finger behavior of male were significantly lower than the female infant monkeys ( P <0.05 ) .There was no significant difference of sucking toe behavior .Conclusions 7 behaviors were recorded during the whole stage of observation , huddling behavior , pacing behavior , sucking toe behavior , sucking finger behavior , sucking genitalia behavior , sucking body of companion behavior and mounting behavior respectively , and 7 behaviors were increased by degrees with time .Huddling behavior to reflect fear psychology;sucking behavior to represent physiological demand and defensive psychology ;pacing was insignificant behavior in the initial stage , then to reflect psychological anxiety of rhesus monkeys .Provided a way and model on assessment of psychology, praxiology, to study and research the change of psychological state and behavior of early weaning infants .
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Macaque monkeys are good sentinel to humans for environmental pollutions because their similarities in genetic and physiological characteristics. So, their reference values about exposures to heavy metals are required for proper data interpretation. Here, we report several heavy metals concentrations in the hair of rhesus monkeys which are widely used in biomedical research. The hair of 28 imported rhesus monkeys from an animal farm in southwest China were examined for the presence of eight heavy metals (Arsenic, Beryllium, Cadmium, Chromium, Iron, Lead, Mercury, and Selenium). The analyzed data in parts per million (ppm) for hair concentrations of heavy metals in rhesus monkeys were as follow: As (0.654+/-0.331), Be (0.005+/-0.003), Cd (0.034+/-0.022), Cr (11.329+/-4.259), Fe (87.106+/-30.114), Pb (0.656+/-0.613), Hg (0.916+/-0.619), and Se (3.200+/-0.735). The concentrations of Be, Cr, and As showed significant higher in females than in males (P<0.05). We present here the reference values of several heavy metals in healthy China-origin rhesus monkeys. These data may provide valuable information for veterinarians and investigators using rhesus monkeys in experimental studies.
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Animals , Female , Humans , Male , Beryllium , Cadmium , China , Chromium , Hair , Haplorhini , Iron , Macaca , Macaca mulatta , Metals, Heavy , Nitriles , Pyrethrins , Reference Values , Research Personnel , VeterinariansABSTRACT
0.05).In1?g/kg dosage group,no neutralizing activity was detected at the end of convalescent period.CONCLUSION:The neutralizing antibodies can be detected in the serum of both hamsters and rhesus monkeys after repeating injection of recombinant consensus interferon?.The titers of antibody are in direct ratio with the duration and the injected dose.
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Objective To observe humoral and cellular immunogenecity of nucleic acid vaccine of hepatitis B core antigen (HBcAg) in rhesus monkeys. Methods Rhesus monkeys of the experimental group and the control group received intramuscular injections of a HBcAg nucleic acid vaccine(pJW4303/HBc) and a control plasmid (pJW4303), respectively. Anti HBc titers, isotypes of anti HBc IgG in sera of the rhesus monkeys pre and post vaccinations, and IFN ? as well as IL 4 levels in the culture supernatant of PBMC isolated from the monkeys were detected by an enzyme linked immunoabsorbent assay. HBcAg specific proliferation activities of PBMC in the monkeys were measured by 3H TdR incorporation assay. Results It was observed in rhesus monkeys of experimental group an obvious anti HBc response after immunization with HBcAg nucleic acid vaccine. The major isotypes of anti HBc IgG was IgG2 and IFN ? was predominant compared with IL 4 in the culture supernatant of rhesus monkeys' PBMC, both indicating Th1 type of immune responses. HBcAg specific proliferation activities of PBMC in the experimental group were significantly stronger than those in the control group. Conclusions The nucleic acid vaccine based on HBcAg shows a good humoral and cellular immunogenecity in rhesus monkeys.
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OBJECTIVE: To establish a RP-HPLC method for concentration determination of m-nisoldipine (m-Nis) in the plasma of rhesus monkeys.METHODS: The analysis was performed on a C18 column at 30℃ with a mobile phase of methanol-water (63∶37) at a flow rate of 1.0ml/min.The detection wavelength was 236nm.The sensitivity was 0.05AUFS and the internal standard was nimoldipine.RESULTS: The detectable concentration of m-Nis showed good linearity in the range of 1.75～ 448?g/L.The average recovery of extraction was 84.1%(RSD=4.09%), and the average recovery of method was 98.7%(RSD=2.76%).The processed plasma samples remained stable in quality after having been stored for 7 days, and the plasma remained stable in quality through repeated freeze thawing or stored at low temperature.CONCLUSION: The present method is highly sensitive and reproducible, as well as convenient, which can be used for concentration determination of m-Nis in the plasma of rhesus monkeys.