Controlled Gastric Emptying. II. In Vitro Erosion and Gastric Residence Times of an Erodible Device in Beagle Dogs

An erodible gastric retention device fabricated from various polymeric blends was examined in vitro for its dissolution properties and in vivo in fasting dogs for assessment of its gastric retention potential. Dissolution studies were conducted with extruded rods of polymer blends to assess their potential as candidates for the erodible component of a gastrically retained device. Based on results from dissolution studies, rods of poly(ortho ester)/polyethylene blends (POE/PE) (45% erosion at pH 1.5 and 24 hr) were used to fabricate arms for tetrahedron-shaped devices. Corners for the tetrahedral device were fabricated from Silastic 382 loaded with 15% barium sulfate for X-ray visualization. Beagle dogs were dosed with tetrahedron-shaped test devices administered in gelatin capsules and gastric retention monitored by X ray over a 24-hr period. A comparison of in vitro erosion rates and in vivo performance of various polymer blends indicated a definite trend for increased gastric retention of devices made from the more slowly eroding blends. The results indicate that the blending of erodible and nonerodible polymers is a valid approach for obtaining materials that will provide the necessary structural properties to achieve gastric retention yet lose integrity within a desired time.     

冲顶式上颌窦底提升植骨同期牙种植的实验研究

[目的]探讨用Summer's骨凿冲顶提升上颌窦底后窦底骨质和黏骨膜改变情况以及种植体与周围组织结合生物学变化,为临床应用该项技术提供进一步可靠的实验依据.[方法]16只狗随机分为提升高度不同(2 mm、4 mm)2组,每只狗植入种植体4枚,一侧植骨,一侧不植骨,在不同时间(3、6、12、24周)取材.标本经大体观察,放射检查,组织学检查,四环素荧光检查,抗BMP-2免疫组化检测.[结果]移植骨愈合良好,种植体形成骨结合,提升4 mm不植骨种植体顶端无骨形成.[结论]上颌窦提升2 mm种植体顶端有骨存在,提升4 mm时,植入种植体顶端多数情况下无骨存在.     

Acute Circulatory Effects of Doxorubicin in the Conscious Dog

Experimental work on the mechanisms of acute doxorubicin-induced cardiotoxicity may contribute to a better understanding of the clinical problem of cardiac failure after treatment with anthracycline derivatives. We studied aortic pressure and heart rate continuously for 1 h following a bolus injection of doxorubicin (1 mg/kg) in 7 dogs. In contrast with previous studies in intact animals, no anesthesia was used in order to eliminate possible interactions of doxorubicin with other drugs. One minute after doxorubicin injection a severe hypotension was observed, the average nadir in systolic and diastolic pressure being 62% and 42% of initial values. Surprisingly, the decrease in arterial blood pressure was not accompanied by cardiac acceleration. Doxorubicin, apparently interferes with the normal regulation of heart rate through the baroreceptor control system. Although several theories have been put forward regarding the mechanisms governing acute anthracycline cardiotoxicity, our knowledge of the phenomenon is still incomplete.     

山莨菪碱对失血性休克狗红细胞变形能力的作用—抗休克机制的研究

为探讨山良菪碱抗休克的机制,将15只失血性休克狗分为两组进行实验。山莨菪碱组:动物失血后静滴山莨菪碱(10mg/kg)20分钟;对照组则静滴同量生理盐水。实验过程中,在失血前、休克期和回输血液后分别从股动脉采血检查红细胞形态及其变形能力。结果:对照组在休克一小时和二小时,红细胞有部分皱缩并且变形能力降低,与休克前比较有显著性差异(P<0.05)。山茛菪碱组的红细胞形态和变形能力在失血前后则无明显差异,甚至在失血后第一小时其变形能力有所提高。以上说明山茛菪碱有维持正常红细胞形态和变形能力的作用。     

Withania somnifera extract. Its effect on arterial blood pressure in anaesthetized dogs

The effect of Withania somnifera extract on arterial blood pressure in ‘normotensive’ pentobarbital anaesthetized dogs was studied. Also a possible effect of Withania somnifera on blood pressure in dogs administered either with adrenaline and acetylcholine was investigated. Thirty mongrel dogs of both sexes were distributed randomly in three series of ten animals each. Each animal was adminstered at intervals of 4 min with either a neurotransmitter, saline or the extract until a cycle of 32 minutes was completed. It is concluded that the Withania somnifera extract induced a significant decrease (p < 0.05) in the arterial and diastolic blood pressure in ‘normotensive’ pentobarbital anaesthetized dogs. Withania also significantly prevented the hypotensive effect of acetyltholine and increased the hypertensive effect of adrenaline.     

Blood-CSF barrier to CCK and effect of centrally administered bombesin on release of brain CCK

The purpose of this study, in part, was to determine the ability of cholecystokinin (CCK-33/39 and CCK-8) to penetrate the blood cerebrospinal fluid (CSF) barrier in dogs by measuring these forms of CCK in plasma and in CSF. In addition, the effectiveness of centrally administered bombesin in releasing brain CCK-33/39 and CCK-8 was evaluated. Six groups of five dogs each were studied. Each group received one of the following: (1) intravenous infusion of CCK-33/39 (1.3 micrograms/kg/hr); (2) intravenous infusion of CCK-8 (0.4 micrograms/kg/hr); (3) intrathecal infusion of CCK-33/39 (1.3 micrograms/kg/hr); (4) intrathecal infusion of CCK-8 (0.5 micrograms/kg/hr); (5) intravenous infusion of bombesin (1 micrograms/kg/hr); and (6) intrathecal infusion of bombesin (1 microgram/kg/hr). Plasma concentrations of CCK-33/39 significantly increased during intravenous infusion of CCK-33/39 (from basal of 84 +/- 8 to 142 +/- 2 pg/ml) or bombesin (from basal of 78 +/- 13 to 325 +/- 87 pg/ml); however, CSF perfusate concentrations of CCK-33/39 did not increase. CCK-33/39 levels of the CSF perfusate increased significantly (P less than .05) from 211 +/- 84 to 9,873 +/- 3,368 pg/ml during intrathecal infusion of CCK-33/39, but failed to rise simultaneously in the systemic circulation. Similarly, intravenous infusion of CCK-8 caused a fivefold elevation in plasma CCK-8 levels and no change in CSF perfusate levels of CCK-8; moreover, intrathecal infusion of CCK-8 failed to elevate peripheral CCK-8 levels, despite CSF perfusate CCK-8 levels of 92,300 +/- 18,598 pg/ml. Intrathecal concentrations of neither CCK-33 nor CCK-8 were affected by intravenous or intrathecal administration of bombesin. We conclude that CCK-33/39 and CCK-8 do not penetrate the blood-cerebrospinal fluid barrier in dogs, and centrally administered bombesin is ineffective in causing release of cholecystokinin from brain tissue into the CSF.     

Intracarotid infusion of PCNU (NSC: 95466): Preclinical toxicological study in dogs

The prognosis of patients with unresectable intracerebral primary and metastatic tumours that recur following cranial irradiation is poor. Chemotherapy agents have been of limited value. PCNU — a new nitrosourea, has been shown to have the optimum log P for treatment of murine intracerebral tumours. We conducted a preclinical toxicological study of intracarotid injection of PCNU in dogs. Our results show that there was no major neurological or retinal toxicity from the drug, suggesting that PCNU may be less toxic than the presently available BCNU.     

Methicillin-Resistant and -Susceptible Staphylococcus aureus Infections in Dogs

Methicillin-resistant Staphylococcus aureus (MRSA) has become a pathogen of animals. To compare types of infections, clinical outcomes, and risk factors associated with MRSA in dogs with those associated with methicillin-susceptible Staphylococcus aureus (MSSA) infections, we conducted a case–control study at 3 veterinary referral hospitals in the United States and Canada during 2001–2007. Risk factors analyzed were signalment, medical and surgical history, and infection site. Among 40 dogs with MRSA and 80 with MSSA infections, highest prevalence of both infections was found in skin and ears. Although most (92.3%) dogs with MRSA infections were discharged from the hospital, we found that significant risk factors for MRSA infection were receipt of antimicrobial drugs (odds ratio [OR] 3.84, p = 0.02), β-lactams (OR 3.58, p = 0.04), or fluoroquinolones (OR 5.34, p = 0.01), and intravenous catheterization (OR 3.72, p = 0.02). Prudent use of antimicrobial drugs in veterinary hospitals is advised.     

失血性休克狗微循环和血液流变学的变化

在9只失血性休克狗(平均血压维持在40mmHg)观察其球结膜微循环,并定期从股动脉采血检查血液和血浆比粘度、红细胞比容、血小板聚集和红细胞变形能力。结果:一、微循环反应非常敏感,放血后数分钟球结膜微动收缩,血流速度变慢,红细胞出现聚集;休克期镜下可见毛细血管数目减少,血流停滞,红细胞重度聚集。二、血液流变学检查:放血停止后,血液和血浆比粘度,红细胞比容均明显下降;血小板聚集加强;红细胞变形能力的变化发生较晚,休克后一小时开始降低。三、回输失去的血液和生理盐水后,微循环和血液流变学诸指标都趋向恢复。作者分析了失血性休克狗微循环和血液流变学的关系。