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@#Objective To verify the feasibility of a self-designed magnetic anchoring and traction device (MATD) for assisting two-port video-assisted thoracoscopic esophagectomy. Methods Three Beagle dogs were selected as animal models with age ranging from 1-6 years and weight ranging from 8-12 kg, and they underwent two-port video-assisted thoracoscopic esophagectomy after general anesthesia. We used the MATD to retract the esophagus to different directions, which assisted mobilizing esophagus, detecting the nerves along esophagus and dissecting paraesophagus lymph nodes. The operation time, blood loss and feasibility of the MATD were recorded. Results With the aid of the MATD, we successfully retracted and mobilized the esophagus, detected the nerves and dissected the lymph nodes in three Beagle dog models. During the operation, the MATD provided sufficient and steady traction of esophagus to achieve a good exposure of the operative field, effectively decreasing the interference between working instruments. The MATD worked well. The mean operation time was 30 min, and the mean intraoperative blood loss was about 10 mL. Conclusion It is effective to use the MATD to assist retracting esophagus during video-assisted thoracoscopic esophagectomy. The magnetic anchoring and traction technique can assist to expose the surgical field, decrease the interference between the working instruments and have the potential clinical application.
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Objective:To observe the possible toxicity of long-term intravenous injection of Tanreqing injection in Beagle dogs， so as to provide experimental data for its clinical safe medication. Method:A total of 32 Beagle dogs （16 males and 16 females） were randomly divided into the low- （2.5 mL·kg<sup>-1</sup>）， medium- （5.0 mL·kg<sup>-1</sup>）， and high-dose （10.0 mL·kg<sup>-1</sup>） Tanreqing injection groups and control group according to their body mass indices， with eight dogs in each group. In the waking state， the dogs were treated with intravenous injection of corresponding drugs into the medial cephalic vein of forelimb for 13 weeks， followed by four-week drug withdrawal. After the observation of general condition， body mass， and food consumption， the Beagle dogs were subjected to electrocardiography， ophthalmoscopy， hematological examination， serum biochemistry， and blood coagulation test in the middle of medication （week 6）， at the end of medication （week 13）， and during recovery （week 17）. Then the gross anatomy was conducted for calculating the major organ coefficients and observing the histopathological changes. Result:No obvious toxic reaction was found in each group， but the decreased fibrinogen and increased Kupffer's cells phagocytizing yellow-brown pigment in hepatic sinusoids were observed in the high-dose Tanreqing injection group following three months of medication. Reduction of fibrinogen was not observed in recovery period， but Kupffer's cells that phagocytized yellow-brown pigment still existed. Conclusion:The intravenous injection of Tanreqing injection at 2.50 mL·kg<sup>-1 </sup>（low dose）， 5.00 mL·kg<sup>-1</sup> （medium dose） or 10.00 mL·kg<sup>-1 </sup>（high dose） for three months in Beagle dogs resulted in no obvious toxic reaction. However， it is still suggested to test the liver function and blood coagulation after long-term administration of high-dose Tanreqing injection.
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OBJECTIVEP: To investigate the toxicokinetic and tissue distribution of vitexin in Beagle dogs. METHODS: Beagle dogs were randomly divided into three groups, and received vitexin injection at small, medium and big doses of 50, 20 and 8 mg•kg-1. They were given medicine once a day for consecutive 3 months by intravenous drip. The blood samples of Beagle dogs were drawn at different time points on the first and last day of administration, and concentrations in plasma were detected by HPLC method. RESULTS: Intravenous drip the vitexin injection at the doses of 8, 20 and 50 mg•kg-1, the blood concentration of vitexin linearly metabolized in Beagle dogs when given medicine for 1, 22, 44 and 83 d. Vitexin was significantly accumulated in Beagle dogs, and the accumulation was disappeared, and the exposure decreased with the prolonged time at the dose of 50 mg•kg-1; at the dose of 8 and 20 mg•kg-1, vitexin did not accumulate in Beagle dogs, and the exposure decreased with prolonged administration time. CONCLUSION: There is no accumulation of repeated drug delivery in the Beagle dog's body by intravenous drip at the doses of 8 and 20 mg•kg-1.
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Background: Liver reserve function decreases with aging, and at the same time liver histomorphology is degenerated. The incidence and mortality rate of hepatic diseases in elderly people are higher than young people. Aims: To explore the changes and significance of biological molecules in liver tissue of elderly beagle dogs. Methods: Fifteen healthy beagle dogs were divided into young group and aged group. The contents of Bcl-2, Bax, TE, GSK-3, caspase-9, HA, LN, PCIII, Col and CYP1A2 were determined by ELISA. The content of GSH-Px was assessed by biochemical methods. mRNA and protein expressions of PDGF-B, TGF-β1, TGF-β3 were detected by fluorescent quantitative PCR and Western blotting, respectively. Results: Compared with the young group, the contents of regeneration-related molecules Bcl-2, Bax, TE, caspase-9 were significantly increased in aged group (P<0.05), GSK-3 was significantly decreased (P=0.013). The activity of antioxidant molecule GSH-Px and hepatic drug metabolic enzyme CYP1A2 were significantly decreased in aged group than in young group (P=0.012, P=0.006). The contents of liver fibrosis molecules LN, PCIII were significantly increased in aged group than in young group (P<0.05), however, no significant difference in contents of HA and Col were found between the two groups. The mRNA and protein expressions of PDGF-B and TGF-β1 were significantly increased in aged group than in young group (P<0.05); mRNA expression of TGF-β3 was significantly increased (P=0.035), however, the protein expression was significantly decreased (P=0.004). Conclusions: There are a series of molecular biology changes, which are the basis of histomorphological changes in liver tissue of elderly, and its underlying clinical value are deserved to be further studied and developed.
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Objective: To explore the pharmacokinetics of self-made gliclazide modified release tablets in Beagle dogs and to evaluate the in vivo and in vitro correlation. Methods: Six Beagle dogs were orally given self-made gliclazide modified release tablets or reference preparation (DaMeiKang) at a dose of 30 mg with self-control cross-over method. Blood samples were collected at different time points after administration. The gliclazide concentration in plasma was determined by high-performance liquid chromatography, and the pharmacokinetic parameters were calculated. The pharmacokinetic characteristics and relative bioavailability of self-made gliclazide modified release tablets were investigated, the bioequivalence was evaluated, and the in vivo and in vitro correlation was calculated. Results: Area under curve (AUC0-∞) of DaMeiKang was (101.74 ± 20.29) μg/(mL · h), and AUC0-∞ of self-made gliclazide modified release tablets was (95.40 ± 28.68) μg/(mL · h). There were no significant differences in the pharmacokinetic parameters between the test and reference formulations (P>0.05). The relative bioavailability of self-made gliclazide modified release tablets was 93.77%, which was bioequivalent with the reference preparation. The in vitro and in vivo correlation analysis showed that the correlation coefficients of DaMeiKang and self-made gliclazide modified release tablets were 0.912 and 0.894, respectively, which were higher than the critical value (r005.7=0.754). The in vitro release rates of the two preparations were correlated with the in vivo absorption rates. Conclusion: The self-made gliclazide modified release tablets have sustained-release characteristics and bioequivalence with reference preparation. The in vivo absorption behavior of gliclazide modified release tablets can be predicted by the in vitro release assay established in this study.
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OBJECTIVE： To establish a method for blood concentration determination of Fentanyl buccal tablet in Beagle dogs， and to study its pharmacokinetics. METHODS： A total of 6 Beagle dogs were given Fentanyl buccal tablet 1 tablet （675 μg/tablet， buccally）. The blood samples were collected 2， 5， 10， 15， 30， 45， 60， 90， 120， 240， 360， 480， 720 min after administration. After precipitated by methanol， LC-MS/MS method [the determination was performed on Agilent C18 column with mobile phase consisted of methanol-0.02％ formic acid aqueous solution （95 ∶ 5， V/V） at the flow rate of 0.5 mL/min. The sample size was 5 μL and the column temperature was 30 ℃. Mass spectrometric conditions： electrospray ionization source in the multiple reaction monitoring mode was used to detect ions， fentanyl citrate： m/z 337.1→188.0； carbamazepine （internal standand）： m/z 237.1→194.1] was used to determine the blood concentration of fentanyl citrate； the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS： The linear range of fentanyl citrate were 1.0-325.0 ng/mL（r＝0.998）； inter-day RSDs of precision test were lower than 5％ （n＝6）， and intra-day RSDs were lower than 6％ （n＝3）； average recoveries were （94.65±6.32）％-（99.21±3.24）％ （n＝6）. RSDs of matrix effect was lower than 15％ （n＝6）； RE of stability tests were within ±6.2％ （n＝3）. The pharmacokinetic parameters of Fentanyl buccal tablet in Beagle dogs included that tmax was （32.5±6.1） min； t1/2 was （211.8±47.4） min； cmax was （40.3±1.9） ng/mL； CLz/F was （0.006±0.001） L/（min·kg）； AUC0-720 min was （7 564.0±1 576.7） ng·min/mL（n＝6）. CONCLUSIONS： The method is simple， feasible and accurate. Fentanyl buccal tablet have good fast-release and slow-release biphasic release characteristics in Beagle dogs.
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OBJECTIVE： To study the effects of cimetidine on low dose rate irradiation-induced liver cell apoptosis in Beagle dogs. METHODS： Healthy male Beagle dogs were randomly divided into normal control group， model control group， positive drug group （lentinan， 21.33 mg/kg） and cimetidine low-dose， medium-dose and high-dose groups （5.33， 10.67， 21.33 mg/kg）， with 4 Beagle dogs each. Except for normal control group， other groups were given 60Co-γ accumulative irradiation （dosage rate： 0.040 8 mGy/min） for 23 d； the medication groups were given relevant medicine orally before irradiation， once a day. Twenty-four hours after stopping irradiation， TUNEL method was used to detect the apoptosis of liver cells in Beagle dogs. The percentage of apoptotic cells was calculated. The expression level of apoptosis-related proteins （Bax， Bcl-2， Caspase-3， p53） in liver tissue was detected by immunohistochemistry. RESULTS： Compared with normal control group， apoptotic cells and Bax， Caspase-3， p53 positive cells were increased significantly in liver tissue of Beagle dogs in model control group； the percentage of apoptotic cells， protein expression levels of Bax， Caspase-3 and p53 were increased significantly； Bcl-2 positive cells were decreased significantly， and its protein expression level was decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， above positive cells of liver tissue in Beagle dogs were changed to different extents in medication groups； the percentage of apoptotic cells and protein expression levels of p53 in medication groups， protein expression levels of Bax in positive drug group， cimetidine low-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were decreased significantly； protein expression levels of Bcl-2 were increased significantly in cimetidine groups. The percentage of apoptotic cells in cimetidine medium-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were all lower than positive control group. Protein expression level of p53 in cimetidine low-dose group was significantly higher than positive drug group （P＜0.05 or P＜0.01）. CONCLUSIONS： Cimetidine can inhibit the low dose rate irradiation-induced apoptosis of liver cells in Beagle dogs， and certainly protect liver cells against irradiation. The mechanism of it may be associated with up-regulating the protein expression of Bcl-2 and down-regulating the protein expression of Bax， Caspase-3 and p53 in liver cells.
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Objective To investigate the effectiveness of the affinity adsorption material developed by our team for the specific removal of exogenous endotoxin in the blood circulation. Methods Fifteen beagle dogs were intravenously injected with endotoxin to establish a dog model of endotoxemia, and then they were randomly divided into the treatment group(n=10)and the control group(n=5). The treatment group received an extracorporeal perfusion to remove the endotoxin using the self-made disposable hemoperfusion device,while the control group using routine perfusion device. The levels of endotoxin, tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), interleukin 6(IL-6)and interleukin 8 (IL-8)in the blood of the dogs were measured at the beginning and 120 min after hemoperfusion for 120 minutes. The vital signs of the dogs were monitored during the hemoperfusion. Results After successful establishment of the endotoxemia model,the level of endotoxin at the beginning of hemoperfusion in the treatment group and control group was 118.63 ± 27.98 EU/mL and 117.16 ± 22.95 EU/mL,respectively. After hemoperfusion for 120 min,it was 0.039 ± 0.01 EU/mL and 131.98 ± 7.01 EU/mL, showing a significant difference(P﹤0.05). The clearance rate of hemoperfusion in the treatment group was 94.07%. At the beginning of hemoperfusion, the levels of TNF-α, IL-1β, IL-6 and IL-8 in the treatment group were 1.53 ± 0.27 ng/mL,12.82 ± 1.66 ng/mL,54.77 ± 3.98 ng/mL and 0.25 ± 0.32 ng/mL, and the levels in the control group were 1.53 ± 0.06 ng/mL,13.05 ± 0.18 ng/mL,54.58 ± 0.19 ng/mL and 0.28 ± 0.06 ng/mL, respectively. After hemoperfusion for 120 min, the levels of TNF-α, IL-1β, IL-6 and IL-8 in the treatment group were 0.13 ± 0.06 ng/mL, 0.70 ± 0.36 ng/mL, 1.62 ± 0.80 ng/mL and 0.01 ± 0.00 ng/mL, respectively, and as for the control group,the levels were 2.26 ± 0.15 ng/mL,15.12 ± 0.18 ng/mL,62.54 ± 0.93 ng/mL and 0.73 ± 0.93 ng/mL. There were significant differences between the beginning and after perfusion for 120 min in those two groups(P< 0.05). Conclusions This affinity adsorption material can effectively remove endotoxin and the inflammatory mediators in the blood of experimental dogs,with a clearance rate of 94.07%.
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Objective To investigate the toxicokinetic properties of ginkgolide B(GB) injection after single or repeat-ed administration by intravenous drip in Beagle dogs and to provide evidence for its rational use. Methods Beagle dogs were randomly divided into three groups,and received GB injection at big,medium and small doses of 80,20 and 5 mg·kg-1, re-spectively,by iv drip for 30 min per day and for 6 consecutive days per week for up to 91 days.The blood samples of Beagle dogs were drawn at different time points on the first and last day of administration,and concentrations in plasma were detected by GC-MS method.Toxicokinetic parameters were calculated by DAS pharmacokinetic software and statistically analyzed by SPSS 11.5 software. Results The elimination half-life (t1/2β) of GB at single dose of 5,20,80 mg·kg-1were(110.2±32.6),(115.4± 12.8),(98.6±26.8) min, respectively.The AUC0-twere (61.1±7.4), (348.6±90.5), (2 046.2±356.4) mg·L-1·min,re-spectively.The t1/2βof GB at mutiple doses of 5,20,80 mg·kg-1on the 91rd day were (117.9±28.0),(118.2±17.0),(120.5± 49.4) min,respectively.The AUC0-twere (67.9±14.9), (218.3±31.8), (1 986.4±426.6) mg·L-1·min, respectively.There was no significant difference in main toxicokinetic parameters including t1/2βamong the single or repeated dosage groups, but AUC0-tand Cmaxincreased proportionally with doses. Conclusion The curves of single and repeated intravenous drip of GB in-jection in beagle dogs were in line with the two atrioventricular model,with linear dynamic characteristics and there was no accu-mulation of repeated drug delivery in the body.
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Objective To investigate the injury characteristics of Beagle dogs after warship multi cabin explosion.Methods Forty-eight adult male Beagle dogs were placed in the simulated blast-cabin and adjacent cabin (24 each),and ammunitions respectively containing 0.75kg TNT and 3.50kg TNT were then detonated in the blast-cabin.The survival situation,fluctuation of vital signs,morphological changes of organs and the incidence of various types of injury of the dogs were observed immediately after the explosion to 24h after injury,and the neurological functions score was performed.Results Twenty dogs died immediately after the explosion,and another 9 dogs died 24h after the explosion.The total mortality was 60.42％(29/48),and the mortalities in blastcabin and adjacent cabin were 79.17％(19/24) and 41.67％(10/24),respectively.The dog's skull was penetrated by bomb fragments,and congestion and bleeding were observed in brain tissue,lung,heart,stomach,bowels,liver and kidneys.Extremities fracture,soft tissue contusions,perforation and rupture were also checked out after explosion.The fatality rate of bomb fragment injury,blast injury and combined bomb fragment-blast injury was 27.59％(8/29),17.24％(5/29) and 55.17％(16/29),respectively.Conclusions The combined bomb fragment-blast injury show high incidence and make high fatality rate and serious injury.Combatants should effectually shield themselves with occluded objects as far as possible to avoid damage and reduce fatality.The key of early treatment is to treat the multiple injuries promptly.Intravenous fluid therapy should be practiced after hemodynamic monitoring.
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Objective To investigate the toxic reaction,toxic organs or target tissues of protamine recombinant human insulin (Insulin NPH),and provide basis for clinical trials by single dose toxicity test in mice,repeated toxicity and immunogenicity of Beagle's dogs,and systemic active allergy in guinea pig.Methods ① Using maximum dose method,mice in single dose toxicity test were sc injected with normal saline (NS),vehicle,and Insulin NPH (2092-2488 IU/kg),the toxic reactions after injection were monitored.② In repeated toxicity study,Beagle's dogs were sc administrated with vehicle,the original (Humulin NPH,1.5 IU/kg)and different doses of Insulin NPH (0.5,1.0 and 1.5 IU/kg) for 30 d continuously,followed by a 14-d recovery.During the administration and recovery period,general observation,local irritation,body weight,anus temperature,blood glucose,and electrocardiogram (ECG) were checked,moreover,hematology,serum biochemistry and urine were detected.Also,organic weights and histopathological examination were conducted.Binding antibodies in dog serum were measured by indirect ELISA method in immunogenicity test.③ In systemic active allergy study,cavies were sc injected with low-and high-dose (4 and 12 IU/kg) Insulin NPH,normal saline and vehicle.Besides,ova as positive control was also included.After five times of sensitization test with above doses,the excitation reactions of iv injection with tripled sensitizing doses were observed.Results No obvious toxicity was observed in mice after injected with 165 times of usual clinical dose of Insulin NPH.Repeated toxicity study of Beagle's dogs revealed that 1.0 IU/kg was the no-toxic-effect dose (NOAEL) for Insulin NPH,which was equivalent to 2 times of clinical dose.No bindingantibodies were found in immunogenicity test.There was no obvious allergic symptom in the active systemic allergy study of guinea pig.Conclusion Under the experimental conditions,no serious toxicity of Insulin NPH is found.
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Objective:To study the pharmacokinetics of indometacin (IDM) enteric-coated dropping pills.Methods:Beagle dogs were used as the experimental animals and the marketed IDM enteric-coated tablets were applied as the control,the pharmacokinetics of IDM enteric-coated dropping pills was studied after a single oral administration.DAS software was used for the model fit and parameter calculation,and the bioequivalence was also evaluated.Results:Both IDM enteric-coated dropping pills and tablets were fitted a one-compartment model.Compared with those of IDM enteric-coated tablets,the Cmax,Tmax,AUC0-∞and Tlag of IDM enteric-coated dropping pills all showed notable differences (P<0.05),and the former two increased significantly,and the latter two were shortened significantly.The relative bioavailability of the dropping pills was (121.0±7.7)%.Conclusion:Compared with IDM enteric-coated tablets,IDM enteric-coated dropping pills are with significantly enhanced absorption and shortened lag time,which is worthy of further studies and development.
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OBJECTIVE:To study the pharmacokinetic characteristics of Recombinant hirudin enteric-coated capsule by single and multiple administration in Beagle dogs. METHODS:12 Beagle dogs were divided into single ig group and single iv group by random control method,6 in each group. Recombinant hirudin 0.2 mg/kg was intragastrically administrated or intravenously inject-ed,blood sample was collected;after 2 weeks of cleaning,12 dogs were intragastrically administrated recombinant hirudin 0.2 mg/kg,for 7 d. Sample blood was collected,referred to multiple ig group. Recombinant hirudin concentration in plasma was deter-mined by enzyme-linked immunosorbent assay,and pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS:The results showed that pharmacokinetics by ig and iv recombinant hirudin in Beagle dogs fitted to two-compartment model,abso-lute bioavailability of ig Recombinant hirudin enteric-coated capsule was(14.908±1.868)%;the pharmacokinetic parameters in sin-gle ig group and multiple ig group were tpeak of(2.105±0.243),(3.000±0.000)h,t1/2β of(8.660±2.965),(14.870±2.710)h, cmax of(10.700±0.872),(12.05±1.587)ng/mL,AUC0-1440 min of(55.250±4.386),(58.978±6.002)ng·h/mL,without statistical significances in two groups(P>0.05). CONCLUSIONS:The ig Recombinant hirudin enteric-coated capsule can be absorbed into the blood to a certain extent. There is no accumulation for ig Recombinant hirudin enteric-coated capsule for several days,and it dose not change the pharmacokinetic characteristics.
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Objective: To establish a high performance liquid chromatography-tandem mass spectrometric method ( HPLC-MS/MS) method for the determination of PA-824 in the plasma of Beagle dogs, and study the pharmacokinetics of PA-824 in Beagle dogs. Methods:Carbamazepine was used as the internal standard, and the plasma samples were pretreated with ethyl acetate for the liquid-liquid extraction of PA-824. An Eclipse Plus C18 column (100 mm × 2. 1 mm, 3. 5 μm) was used with the mobile phase consisting of methanol-water (90 :10). The flow rate was 0. 6 ml·min-1 and the column temperature was 30 ℃. The injection volume was 5 μl and the sample analysis time was 5 min. The determination was performed with an electrospray ionization ( ESI) source in the positive multiple reaction monitoring (MRM) mode. The ion pairs were m/z 360. 1→m/z 175. 0 (collision energy of 35, solution cluster volt-age of 65) for PA-824 and m/z 237. 2→m/z 194. 0 (collision energy of 28, solution cluster voltage of 83) for carbamazepine. After the oral administration, PA-824 in plasma was measured at different time points, and then the pharmacokinetic parameters were calcu-lated by DAS 2. 0 software. Results: PA-824 showed a good linear relationship within the range of 50-10000 ng · ml-1 ( r =0. 9991). The recovery was 97. 7%-105. 1%, and the RSDs of intra-day and inter-day were less than 5. 0%. At three different dosa-ges (100, 200 and 500 mg) of PA-824, AUC0-twere (5735. 18 ± 1918. 76),(11548. 47 ± 1838. 04) and (21987. 88 ± 4587. 58) ng·min·ml-1,t1/2 were(14.17 ±5.97),(11.11 ±4.39) and (13.13 ±5.46)h,and Cmaxwere(626.66 ±188.48),(2399.13 ± 516.51) and (4861.33 ±2253.61)ng·ml-1, respectively. Conclusion:The method is simple, accurate, rapid and reproducible, and suitable for the pharmacokinetic study of PA-824 in the plasma of Beagle dogs.
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Sufficient embryos are needed for the preservation of Beagle dogs germplasm resources and the prepara-tion of gene?modified human disease animal models. Up to now, the induced ovulation technique has no effect on dogs,it is hard to obtain mature oocytes in vivo, although the scientists try a lot in many aspects, but still could not make a break?through. The in vitro maturation rate is too low to support the preservation of germplasm resources, application in gene?modified disease models and biomedical research. Aiming to provide useful information on breakthrough in dog oocytes mat?uration, this review will summarize the effect of different age and reproductive stage,different morphology and size of the oo?cytes and lipid droplet on the in vitro maturation of dog oocytes.
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Objective The purpose of this study was to compare two types of myocardial infarction ( MI) models in Beagle dogs. Methods 30 dogs were divided randomly into three groups ( n =10 ) . ① The sham?operated group underwent pericardiotomy but without coronary artery ligation. The other two model groups were made under video?assisted thoracoscopy ( VATS) , where the left anterior descending coronary artery was closed by titanium clips:②The direct vision group:the minimally invasive closure of the artery was performed under direct vision. In this group, the thoracoscopic operation was performed through a 3?0 cm small incision opened at the margin of the left third rib. ③ The thoracoscopic group:the video?assisted thoracoscope was inserted into the chest through a 1?0 cm exploratory hole in the midline of the third rib, and the surgical instruments were inserted through two 0?5 cm operating holes at the para?sternum line of the third rib and midclavicular line of the fourth rib. Electrocardiogram ( ECG) was recorded and the levels of serum creatine kinase?MB ( CK?MB) and troponin I ( cTnI) were measured after modeling. The heart tissue samples were examined by histology using HE staining. The success rate of model establishment, durations from skin incision to chest closing and the wound healing were recorded. Results Compared with the sham?operated group, changes of myocardial infarction were observed in the two model groups ( ECG S?T segment elevation, increased serum CK?MB and cTnI levels, myocardial ischemia and fibrosis, and reduced amount of cardiomyocytes ) . The survival rate was 90% in both of the two model groups. The operating time was shorter in the minimally invasive surgery under direct vision group, and the wound healing time was shorter in the thoracoscopic group. Conclusions The myocardial infarction models generated by minimally invasive surgery have less trauma and low mortality in the dogs. This model is suitable for investigation of pathophysiological mechanism associated with myocardial infarction.
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Shenfu Injection (SFI) is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rc) and aconitum alkaloids (benzoylmesaconine and fuziline) were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPLC-MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2-8 mL/kg.
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Background:It has been demonstrated that H + -K + -ATPase expression in human parietal cells had a tendency to increase with aging. However,the effect of aging on activity of H + -K + -ATPase is still unclear. Aims:To investigate effect of aging on activity of H + -K + -ATPase. Methods:Fifteen male Sprague-Dawley(SD)rats were divided into 4,21,24, 27 and 30 months group,and 19 healthy beagle dogs were divided into younger group,junior elderly group and senior elderly group. The activity of H + -K + -ATPase in gastric fundal mucosa was assessed. Results:The activity of H + -K + -ATPase in gastric fundal mucosa in 4,21,24,27 and 30 months old rats were(4. 850 ± 0. 312)μmol·mg - 1 ·h - 1 , (5. 466 ± 0. 379)μmol·mg - 1 ·h - 1 ,(6. 068 ± 0. 228)μmol·mg - 1 ·h - 1 ,(5. 733 ± 0. 767)μmol·mg - 1 ·h - 1 and (6. 223 ± 0. 428)μmol · mg - 1 · h - 1 ,respectively. With aging,H + -K + -ATPase activity in rats had a tendency to increase(F = 4. 519,P = 0. 031). The activity of H + -K + -ATPase in beagle dogs in younger group,junior elderly group and senior elderly group were(11. 087 ± 4. 320)μmol·mg - 1 ·h - 1 ,(8. 549 ± 3. 250)μmol·mg - 1 ·h - 1 ,(12. 071 ± 2. 820)μmol·mg - 1 ·h - 1 ,respectively. There was no statistically significant difference among the three groups(F =1. 339,P = 0. 290). Conclusions:With aging,the activity of H + -K + -ATPase in rats and beagle dogs does not decline, but even has a tendency to increase.
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OBJECTIVE:To study the pharmacokinetics of the active ingredients of Shenmai injection,including ginsenoside Rg1 and ginsenoside Re,in normal Beagle dogs and those with myocardial ischemia. METHODS:6 Beagle dogs were given isopro-terenol hydrochloride (1.1 mg/kg) sc to establish the model of myocardial ischemia (model group). Another 6 Beagle dogs were given isometric normal saline (2.2 ml/kg) sc as controls group. The two groups of dogs respectively received corresponding drugs sc at 8:00 am and 13:00 pm on day 1 and at 8:00 am on day 2. Each group of dogs were given Shenmai injection(1.6 ml/kg)iv 1 h after administration on day 2,and such intravenous drip lasted for about 1 h. Blood was collected from each group 0,0.25, 0.5,0.75,1(the end of iv),1.5,2,3,4,6,8,12 and 24 h from the start of iv. Liquid chromatography-mass spectrometry was adopted to determine the concentrations of ginsenoside Rg1 and ginsenoside Re in blood,and WinNonlin 6.3 was used to calculate pharmacokinetic parameters for comparison. RESULTS:For ginsenoside Re in the dogs of the model group,t1/2 was(2.69±1.12) h,AUC0-24 h was(2 060.78±812.18)h·μg/L,Vz was(46.16±20.98)ml and CL was(9.02±4.45)ml/h;compared to the normal control group,AUC0-24 h was much greater and Vz and CL were significantly lower,showing a statistically significant difference(P0.05). CON-CLUSIONS:Myocardial ischemia may affect the removal of ginsenoside Re in Beagle dogs,but has no effect on the pharmacoki-netic process of ginsenoside Rg1.
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Objective To establish the normal reference ranges of clinical pathology for Beagle dogs in the Good Laboratory Practice ( GLP ) system.Method Sixteen biochemical indexes , seventeen hematological indexs and three coagulation function indexes of 117 Beagle dogs were detected , and the mean value of each index and the normal reference ranges were calculated and compared .Results Only alkaline phosphatase ( ALP ) from the biochemical items was significantly different between males and females (P<0.01),which was higher among males than among females .Three in-dexes of hematology were significantly different between males and females (P<0.01),with red blood cell(RBC), hemo-globin(HGB)and hematocrit(HCT)lower among males than among females.The coagulation function items were not signif-icantly different between the two sexes .Conclusion Some indexes of clinical pathology were significantly different between males and females , which should be considered during statistic analysis on toxicity .Our study has established the normal reference range of clinical pathology for Beagle dogs in the GLP system , which provides reference for toxicity tests .