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Abstract Introduction: The endoparasite Dendrogaster argentinensis infects the intertidal brooder sea star Anasterias antarctica. This sea-star species is in the highest trophic level in the Beagle Channel. Objective: To study the effects of parasitism by D. argentinensis on the fitness and reproduction of A. antarctica. Methods: Adults from the brooder sea-star were collected from the rocky intertidal of Ensenada Zaratiegui bay (54°51' S & 68°29' W), Argentina. Eight seasonal samplings were performed (four seasons in two years) in the upper and low intertidal. During dissection, parasites were removed, and all organs were extracted and weighed separately. Results: Dendrogaster argentinensis prevalence was the highest for the region (20.4 %). Parasitized individuals were more frequent in the low intertidal in all seasons, with a higher difference in summer, where it is likely that the higher temperatures and strong winds could make the upper intertidal more challenging for a parasitized individual. Five parasitized individuals were castrated. Generally, the gonadal (GI) and somatic (pyloric caeca, PCI; stomach, SI; body wall, WI) indexes were lower in parasitized than non-parasitized individuals. Conclusions: Parasitism by D. argentinensis negatively affects A. antarctica condition. It affects reproduction because it reduces the GI, and can also produce castration. The parasite competes for the sea-stars' energetic resources, also decreasing the individual's capacity for feeding (reduced stomach) and growth (reduced body wall).
Resumen Introducción: El endoparásito Dendrogaster argentinensis infecta a la estrella de mar Anasterias antarctica, especie que se encuentra en el nivel trófico más alto del Canal Beagle. Objetivo: Estudiar los efectos del parasitismo de D. argentinensis en la condición fisiológica y reproducción de A. antarctica. Métodos: Adultos de la estrella de mar incubadora fueron recogidos del intermareal rocoso de la bahía Ensenada Zaratiegui (54°51' S & 68°29' W). Se realizaron ocho muestreos estacionales (cuatro temporadas en dos años) en el intermareal superior y bajo. Durante la disección, se removieron los parásitos, y todos los órganos, los cuales fueron pesados por separado. Resultados: La prevalencia de D. argentinensis fue la más alta de la región (20.4 %). Los individuos parasitados fueron más frecuentes en el intermareal bajo en todas las estaciones, siendo la mayor diferencia en verano, donde es probable que las temperaturas más altas y los fuertes vientos puedan hacer que el intermareal superior sea más desafiante para un individuo parasitado. Se observaron cinco individuos parasitados que estaban castrados. Generalmente, los índices gonadales (GI) y somáticos (ciego pilórico, estómago, y pared del cuerpo) fueron menores en los individuos parasitados que no parasitados. Conclusiones: El parasitismo de D. argentinensis afecta negativamente la condición fisiológica de A. antarctica. Afecta a la reproducción en términos de bajo GI y puede causar castración. El parásito compite por los recursos energéticos de las estrellas de mar, disminuyendo también la capacidad del individuo para alimentarse (reducción del estómago) y crecer (reducción de la pared del cuerpo).
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Animals , Parasites/microbiology , Starfish/parasitologyABSTRACT
Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.
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Objective:To investigate the method of determining oral implantation sites based on an anatomical model of mandibular premolar area of a Beagle dog.Methods:This study was performed in the Second Affiliated Hospital of Zhejiang Chinese Medical University between January 2019 and October 2020. Mandibular anatomical structure and measurement data were compared between before and after removal of premolar teeth to determine safe implantation areas and oral implantation sites.Results:Among all mandibular premolars, the roots of the 1 st to 4 th premolars (P1-P4) gradually increased. The diameter of the mesial roots of the double root teeth P2, P3, and P4 was (2.72 ± 0.45) mm, (3.22 ± 0.32) mm, (4.16 ± 0.34) mm, respectively, which was significantly shorter than those in the distal roots [P2: (2.98 ± 0.29) mm, P3: (3.48 ± 0.27) mm, P4: (4.58 ± 0.22) mm]. The length of distal roots P2, P3 and P4 was (8.79 ± 0.41) mm, (9.21 ± 0.31) mm, (10.12 ± 0.36) mm), respectively, which was significantly shorter than that of mesial root [P2: (8.91 ± 0.69) mm, P3: (9.48 ± 0.27) mm, P4: (11.58 ± 0.24) mm]. Among all mandibles, the distance (H) from the mental foramen to the first molar and the width (W) of the alveolar crest increased successively [H1: (7.24 ± 0.49) mm, H2: (8.28 ± 0.71) mm, H3: (9.52 ± 0.37) mm, W1: (5.71 ± 0.81) mm, W2: (5.82 ± 0.28) mm, W3: (6.72 ± 0.54) mm]. Conclusion:The mental foramen and the distal part outside the canine apical area are safe implantation areas. In the safe implantation area, the length and diameter of the implant prosthesis do not exceed the root length in the implantation area and the maximum diameter in the buccal lingual direction.
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A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine the plasma concentration of progesterone in Beagle dogs, and apply it to the study of the pharmacokinetics of progesterone sustained-release formulation in Beagle dogs. The plasma samples were processed by protein precipitation method and megestrol acetate was used as an internal standard (IS). The quantitation analysis was performed using multiple-reaction monitoring (MRM) mode at the specific ion transitions of m/z 315.2→97.0 for progesterone and m/z 385.2→267.1 for megestrol acetate (IS) under the positive ion condition. Male Beagle dogs were injected intramuscularly with progesterone sustained-release microspheres and the plasma samples were collected at different time points after administration. The relevant pharmacokinetic parameters were calculated by WinNonlin 8.1 software. A good linearity over the range of 0.1-500.0 ng·mL-1 was yielded by this method. The intra- and inter-day precision (RSD) were all less than 13.25% and the accuracy (RE) was within 8.92%. Stability test showed that progesterone in dog plasma was stable at room temperature for 12 h, up to 60 days at -20 ℃ and after three cycles of freeze-thaw. The recovery of it ranged from 71.43%-77.97%. After intramuscular injection of progesterone sustained-release microspheres in Beagle dogs, tmax was 19.00 ± 25.36 h, Cmax was 137.72 ± 11.59 ng·mL-1, t1/2 was 83.83 ± 26.43 h. The drug was released continuously in vivo and in a continuous absorption process for many times with good sustained-release effect. The method developed in this study is sensitive, rapid and stable. It is suitable for the determination of progesterone plasma concentration in Beagle dogs, and can be applied to the preclinical pharmacokinetic study of progesterone-related formulations. The animal experiment scheme of this study was approved by the Animal Ethics Committee of the Academy of Military Medical Sciences.
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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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@#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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The aim of this study was to investigate the influence of enhanced external counterpulsation (EECP) on the cardiac function of beagle dogs after prolonged ventricular fibrillation. Twenty-four adult male beagles were randomly divided into control and EECP groups. Ventricular fibrillation was induced in the animals for 12 min, followed by 2 min of cardiopulmonary resuscitation. They then received EECP therapy for 4 h (EECP group) or not (control group). The hemodynamics was monitored using the PiCCO2 system. Blood gas and hemorheology were assessed at baseline and at 1, 2, and 4 h after return of spontaneous circulation (ROSC). The myocardial blood flow (MBF) was quantified by 18F-flurpiridaz PET myocardial perfusion imaging at baseline and 4 h after ROSC. Survival time of the animals was recorded within 24 h. Ventricular fibrillation was successfully induced in all animals, and they achieved ROSC after cardiopulmonary resuscitation. Survival time of the control group was shorter than that of the EECP group [median of 8 h (min 8 h, max 21 h) vs median of 24 h (min 16 h, max 24 h) (Kaplan Meyer plot analysis, P=0.0152). EECP improved blood gas analysis findings and increased the coronary perfusion pressure and MBF value. EECP also improved the cardiac function of Beagles after ROSC in multiple aspects, significantly increased blood flow velocity, and decreased plasma viscosity, erythrocyte aggregation index, and hematocrit levels. EECP improved the hemodynamics of beagle dogs and increased MBF, subsequently improving cardiac function and ultimately improving the survival time of animals after ROSC.
Subject(s)
Animals , Male , Dogs , Counterpulsation/methods , Cardiopulmonary Resuscitation/methods , Hemodynamics/physiology , Case-Control Studies , Disease Models, Animal , Kaplan-Meier EstimateABSTRACT
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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The goal of the present study was to determine the effectiveness and safety of hemoperfusion (HP) in beagle dogs with chronic kidney disease (CKD). The experimental protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Institute of Pharmaceutical Research New Drug Evaluation Research (IACUC2019071501). Twelve CKD model beagles were randomly divided into two groups: a low-frequency treatment group (n = 6) and a high-frequency treatment group (n = 6). The dogs in the high- and low-frequency groups received HP treatment every 3 days and once per week, respectively, for two treatments, with each session lasting 2 h. The test results showed that high-frequency HP treatment significantly decreased the accumulation of toxins in the CKD beagles. Hematology, coagulation function, electrolytes and liver function indicated that the HP treatment was safe. The body index effects were consistent between the low- and high-frequency treatment groups. Therefore, HP treatment once every 3 days was safe at the animal level. Multiple HP treatments every 3 days were more conducive than weekly treatments to the removal of uremic toxins with better prognosis and had no associated safety hazards.
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Objective: In order to evaluate the reliability and feasibility of pueraria reference extractive substance (RES) used in biological sample, the pharmacokinetics of 3′‑hydroxy puerarin (3′-HP), puerarin, 3′‑methoxy puerarin (3′-MP), and daidzein-8-C-apiosyl-(1-6)-glucoside (DAG) in beagle plasma following oral administration of Yufeng Ningxin Tablet were quantitated. Methods: A reliable and sensitive high-performance liquid chromatography-tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method developed with chromatographic separation was operated on a Merck C18 column, and acetonitrile-5 mmol/L ammonium was used as mobile phase in gradient elution. The plasma samples were deproteinized by acetone, detected by triple quadrupole mass spectrometry with an electrospray ionization interface, and quantified using selected ion monitoring mode. The pharmacokinetic parameters were calculated by Winnonlin 4.1. Results: The calibration curves of the reference extractive substance and standard substance methods were linear over the ranges 0.0417–11.3309 µg/mL and 0.0394–10.0000 µg/mL. The intra-day and inter-day precision of the two methods at three concentrations were less than 13.63%, and the average recoveries of 3′-HP, puerarin, 3′-MP, and DAG were more than 70.67%. The RSD of the mean plasma concentrations of the analytes calculated by the two methods was less than 5%, and cos (ϑ) = =1.000. Among the analytes, puerarin showed the highest blood concentration [(940 ± 185) ng/mL] and the longest retention time [(5 ± 1) h] in the dog's bodies. Conclusion: Pueraria reference extractive substance can be seen as an alternative to the standard substance to overcome the scarcity of standard substance for the analysis of biological samples.
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OBJECTIVE: To study the effect of cimetidine on the histopathology and the expression of SOD2, GPX1 gene and protein in low-dose accumulative irradiated Beagle dogs spleen and to investigate the mechanism of cimetidine′s protective effect on low-dose accumulative irradiation. METHODS: Twenty-four male Beagle dogs were divided into six groups: normal control group,model group,positive drug control group and cimetidine groups at the dose of 5.33, 10.67, 21.33 mg•kg-1 respectively. The dogs were irradiated with 60Co-γ-ray at 0.040 8 mGy•min-1 rate for 23 d. Cimitidine was administered intragastrically during irradiation, once a day. Microscope was adopted to observe the pathologic change of spleen and the expression levels of SOD2,GPX1 gene and protein in the spleen tissue of dogs were detected by qRT-PCR and immunohistochemistry techniques. RESULTS: Compared with the model group,cimetidine ameliorated the pathological changes and ultrastructure lesions in the spleen of dogs. Also compared with the model group, the levels of SOD2 and GPX1 protein in cimetidine groups at the dose of 5.33, 10.67, 21.33 mg•kg-1 were higher(P<0.05) and the levels of SOD2 and GPX1 mRNA of the three cimetidine groups were increased significantly(P<0.01). CONCLUSION: Cimetidine can reduce the histological damage. Cimetidine can upregulate the expressions of SOD2 and GPX1 gene and protein and it has good protective effect on the antioxidant system injury.
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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 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 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 establish a method for the determination of ibrutinib concentration in Beagle dogs， and to compare the pharmacokinetic difference of ibrutinib and its phospholipid complex in Beagle dogs. METHODS： The male Beagle dogs were randomly divided into Ibrutinib suspension group and Ibrutinib phospholipid complex group （using 0.5％ Carboxymethylcellulose sodium solution and water as solvent， mass concentration of 5 mg/mL）， with 3 dogs in each group. All Beagle dogs were given relevant medicine suspension （15 mg/kg） intragastrically， and 2 mL of blood were collected from the forelimb vein before administration and 0.017， 0.083， 0.25， 0.5， 1， 2， 4， 8 and 12 h after administration. Plasma concentration of ibrutinib was were determined by HPLC. Using tolbutamide as internal standard， the determination was performed on Betasil C18 column with mobile phase consisted of acetonitrile-water （contained 0.5％ triethylamine， pH value adjusted to 3.2 with glacial acetic acid）（45 ∶ 55， V/V） at the flow rate of 1.0 mL/min. The detection wavelength was set at 256 nm， and the column temperature was 25 ℃. The sample size was 20 μL. The pharmacokinetic parameters of Beagle dogs in 2 groups were calculated by using DAS 2.1.1 software. The difference of ibrutinib and its phospholipid complex were investigated by t-test. RESULTS： The linear range of ibrutinib was 5-5 000 ng/mL （r＝0.999 8）； lower limit of quantitation was 5 ng/mL； minimum detection limit was 1.3 ng/mL. RSDs of intra-batch and inter-batch were lower than 10％； the accuracy was 98.81％-106.20％； the extraction method did not influence the determination of the substance to be measured. Pharmacokinetic parameters of Ibrutinib suspension and Ibrutinib phospholipid complex with signal intragastric administration were as follows： tmax were（2.00±0.09） and （0.25±0.03）h； cmax were（610.67±21.36） and （2 308.72±100.41）ng/mL； AUC0-12 h were （4 516.67±383.43） and （9 394.16±874.21）ng·h/mL； AUC0-∞ were （6 174.32±525.27） and （10 717.33±897.62）ng·h/mL，with statistical significance （P＜0.05）. The relative bioavailability of Ibrutinib phospholipid complex was 207.99％. CONCLUSIONS： Established HPLC method is simple， specific and sensitive， and can be used for plasma concentration determination and pharmacokinetic study of ibrutinib. The pharmacokinetic parameters of phospholipid complex prepared from ibrutinib changed significantly， drug absorption is accelerated and bioavailability is improved significantly.
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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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SUMMARY: Micro-implant stability has always been the focus of orthodontic clinical research.In the experiment, the morphological changes of bone tissue around the micro-implants in self-tapping and assisting implantation were investigated to explore the effect of different implantation on the osseointegration of micro-implants in order to provide some theoretical basis for clinical practice. Six adult male Beagle dogs were selected,three implants were implanted into the left and right maxillary bone of Beagle dogs at the 0th, 4th and 6th week, respectively. One side to self-tapping implantation, the opposite side to assisting implantation. At the 8th week of the experiment, the animals were sacrificed and the micro-implant-bone tissue specimens with the healing time of 8w, 4w and 2w were obtained.The specimens were stained with Toluidine Blue (TB) and photographed under 100X, 200X microscope. Morphology of microimplant- bone interface cells was observed under light microscope. In self-tapping group, there were some fibrous tissues surrounding the micro-implants at the 2th week, the formation of osteoblasts and osteoid was observed at the 4th week, the wavy and lamellar bone tissues were seen at the 8th week.In assisting group,more collagen fibers were deposited around the micro-implant at the 2th week, there were a large number of osteoid-like cells, and the collagen was gradually replaced by the bone tissue at the 4th week, the osteoblasts were active and the osteoblasts were linear arrange and form a laminate bone at the 8th week.Whether implanted self-tapping or assisted implantation, micro-implant-bone interface reconstruction can occur. If the clinical need for early loading force, micro-implant try to choose selftapping implantation. By appropriately prolonging the healing time, the initial stability of the micro-implant under assistive implantation can be improved.
RESUMEN: La estabilidad del microimplante siempre ha sido el foco de la investigación clínica en ortodoncia. En este trabajo se investigaron los cambios morfológicos del tejido óseo alrededor de los microimplantes autorroscantes y se ayudó a la implantación para explorar el efecto de diferentes implantes en la osteointegración de microimplantes con el fin de proporcionar alguna base teórica para la práctica clínica. Se seleccionaron seis perros Beagle machos adultos, y se colocaron tres implantes en los huesos maxilares izquierdo y derecho en la 0ª, 4ª y 6ª semana, respectivamente. De un lado se colocó el implante autorroscante, y del otro lado el implante asistido. En la octava semana, se sacrificaron los animales y se obtuvieron las muestras de microimplante-hueso con el tiempo de cicatrización de 8, 4 y 2 semanas. Las muestras fueron teñidas con azul de toluidina (TB) y fotografiadas bajo aumento de 100X, y microscopio de 200X. La morfología de las células de la interfaz microimplante-hueso se observó bajo microscopio óptico. En el grupo autorroscante, había tejido fibroso que rodeaba los microimplantes a la 2ª semana, se observó la formación de osteoblastos y osteoide a la 4ª semana y de tejido óseo ondulado y lamelar a la 8ª semana. En el grupo asistido, se depositaron más fibras de colágeno alrededor del microimplante en la 2ª semana, hubo un gran número de células similares a osteoide, y el colágeno fue reemplazado gradualmente por el tejido óseo en la 4ª semana; los osteoblastos estaban activos y se ubicaron linealmente formando un hueso laminado en la 8ª semana. Ya sea que el implante sea con autoasistencia o con implantación asistida, puede ocurrir la reconstrucción de la interfaz microimplante-hueso. Si existe la necesidad clínica de una fuerza de carga temprana, el microimplante de elección sería la implantación autorroscante. Al prolongar apropiadamente el tiempo de curación, se puede mejorar la estabilidad inicial del microimplante bajo implantación asistida.
Subject(s)
Animals , Male , Dogs , Dental Implantation , Orthodontic Anchorage Procedures , Maxilla/anatomy & histology , Maxilla/surgery , OsseointegrationABSTRACT
This study assessed the effects of Weissella cibaria (W. cibaria) CMU on oral health in male and female beagles (n = 18) by measuring oral malodor and periodontal disease-related parameters (calculus, plaque, and gingivitis indices). Oral malodor and indicators of periodontal disease were assessed in five treatment groups: negative control (scaling and 0.24 mg of maltodextrin, n = 3), positive control (0.24 mg of maltodextrin, n = 3), and W. cibaria CMU groups (each n = 4) at low (CMU-L, 2 × 10⁷ colony forming unit [CFU]), medium (CMU-M, 2 × 10⁸ CFU), and high (CMU-H, 2 × 10⁹ CFU) concentrations. After feeding with W. cibaria CMU for 6 weeks, total volatile sulfur compound concentrations in the CMU-L (2.0 ± 1.04 ng/10 mL), CMU-M (2.4 ± 1.05 ng/10 mL), and CMU-H (2.6 ± 1.33 ng/10 mL)groups were significantly lower than in the positive control group (3.2 ± 1.65 ng/10 mL). Also, CMU-L (1.4 ± 0.83 ng/10 mL) and CMU-H (1.9 ± 1.14 ng/10 mL) groups had methyl mercaptan levels lower than that in the positive control group (2.4 ± 1.21 ng/10 mL) at week 2. The plaque index was significantly lower in the CMU-H group (4.5 ± 0.28) than in the positive control group (5.9 ± 1.08) at week 6. W. cibaria CMU could be useful as a novel oral hygiene probiotics for reducing volatile sulfur compounds production and inhibiting plaque growth in companion animals.
Subject(s)
Animals , Dogs , Female , Humans , Male , Gingivitis , Oral Health , Oral Hygiene , Periodontal Diseases , Pets , Probiotics , Stem Cells , Sulfur , Sulfur Compounds , WeissellaABSTRACT
Objective: To evaluate the effect of nickel-titanium three-dimensional memory alloy mesh combined with autologous bone for living model of canine tibial plateau collapse fracture by biomechanical testing. Methods: Sixteen healthy 12-month-old Beagle dogs were randomly divided into 4 group, 4 dogs in each group. The dogs were used to establish the tibial plateau collapse fracture model in groups A, B, and C. Then, the nickel-titanium three-dimensional memory alloy mesh combined with autologous bone (the fibula cortical bone particles), the artificial bone (nano-hydroxyapatite), and autologous fibula cortical bone particles were implanted to repair the bone defects within 4 hours after modeling in groups A, B, and C, respectively; and the plate and screws were fixed outside the bone defects. The dogs were not treated in group D, as normal control. At 5 months after operation, all animals were sacrificed and the tibial specimens were harvested and observed visually. The destructive axial compression experiments were carried out by the biomechanical testing machine. The displacement and the maximum failure load were recorded and the axial stiffness was calculated. Results: All animals stayed alive after operation, and all incisions healed. After 1-3 days of operation, the animals could stand and move, and no obvious limb deformity was found. The articular surfaces of the tibial plateau specimens were completely smooth at 5 months after operation. No obvious articular surface collapse was observed. The displacement and maximum failure load of specimens in groups A and D were significantly higher than those in groups B and C ( P0.05). Conclusion: The nickel-titanium three-dimensional memory alloy mesh combined with autologous bone for subarticular bone defect of tibial plateau in dogs has good biomechanical properties at 5 months after operation, and has better axial stiffness when compared with the artificial bone and autologous bone graft.
ABSTRACT
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.