Glucocorticoids potentiate kainic acid-induced seizures and wet dog shakes

Glucocorticoid effects on kainic acid-induced motor seizures and wet dog shakes in rats were investigated by adrenalectomy and dexamethasone treatment. One-day adrenalectomy attenuated kainic acid-induced wet dog shakes and seizure activity. These effects were restored by dexamethasone. Administration of dexamethasone to non-adrenalectomized rats potentiated kainic acid-induced wet dog shakes and severity of seizure activity. These results suggest that glucocorticoids may play an important role in modulating the severity of kainic acid-induced seizures and wet dog shakes.     

红霉素对犬幽门括约肌压力影响及其与胃动素,生长抑素的关系

为探讨红霉素对犬幽门括约肌的作用及其机理，及其与血浆胃动素，生长抑素的关系。方法采用胃压力测量仪及放射免疫法，同步监测观察了１０条犬静脉滴ＥＭ前后和使用拮抗剂后的幽门压力、血浆ＭＴＬ，ＳＳ的变化，结论：ＥＭ具有增高犬胃幽门压力的作用，其作用机理除与血浆ＭＴＬ有着密切的关系外，血浆ＳＳ也可能共同参与了其调节机制。     

Homologous testis transplantation in dogs

There is growing interest in the possible use of homologous testis transplantation for the treatment of anorchia and male infertility. In order to test the surgical and immunological feasibility of this therapy, three series of experimental studies of homologous testis transplantation were carried out in dogs. In the first pilot study, four beagles from the same litter were transplanted using microsurgical techniques for end-to-end anastomosis of the testicular vessels and the vas deferens. These dogs received cyclosporin A (CyA) for 3 months after transplantation. The longest functional graft survival in this series was 163 days, strongly suggesting that long-term survival of a homologously transplanted testis graft is possible. A second series of operations was performed on ten mongrel dogs. The same surgical technique was employed and the series was divided into three groups. Group 1 received CyA monotherapy, group 2 a combination of CyA and prednisolone, and group 3 received no immunosuppression. The average graft survival time in this series was 18 days, significantly less than the 71 days in the first series. The dogs in group 2, however, had graft survival times that were three times longer than those in the other two groups, suggesting that CyA in combination with prednisolone yields the best graft survival. In the third series, five littermates received a testis graft after castration. Immunosuppression was achieved by administration of CyA and prednisolone for 3 months. In three out of five animals, the graft survived until the immunosuppressive therapy was suspended. Histological biopsies of the graft 3 months after transplantation showed the same maturation of sperm cells as in the control testis of the same dog. The results of the last series suggest that long-term survival of homologously transplanted testis grafts in dogs is, indeed, possible with the aid of CyA and prednisolone. Received: 14 August 1996 Received after revision: 21 March 1997 Accepted: 24 April 1997     

Comparison of the Permeability Characteristics of a Human Colonic Epithelial (Caco-2) Cell Line to Colon of Rabbit,Monkey, and Dog Intestine and Human Drug Absorption

The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.     

Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi

Abstract Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10^?5M) and K⁺ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 times 10^?7 M) and oxyhaemoglobin (1.6 times 10^?5 M), but not affected by atropine (10^?7 M), propranolol (10^?7 M), phentolamine (10^?7 M), indomethacin (10^?6 M), chole-cystokinin (CCK, 10^?8 M) and vasoactive intestinal polypeptide (VIP, 10^?8 M). The relaxation was also abolished by treatment with N^G-nitro-L-arginine (L-NA, 10^?5 M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10^?5 M) and L-NA, but not affected by atropine and N^G-nitro-D-arginine (D-NA, 10^?5 M). The addition of K⁺ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10^?3 M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K⁺ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.     

Initial healing in the dog of submerged versus non‐submerged porous‐coated endosseous dental implants

It has previously been reported that porous‐coated root form endosseous dental implants, became well integrated when used in the traditional 2‐stage surgical approach. In this study, the placement of the implant in a 1‐stage (non‐submerged)technique was to be explored. Implants were placed in the mandibles of dogs, and 2 designs were used differing only in that one (experimental) had a 3mm transgingival extension, permitting it to be exposed lo the oral cavity from the outset. 12 (3 per animal) non‐submerged implants were placed on I side of 4 beagle dogs and 12 control (submerged) implants were placed contralaterally. All implants were allowed to heal for 6 weeks, after which histological preparations were made. 2 of 12 non‐submerged implants were lost due to post‐operative complications: otherwise, all implants healed uneventfully. Histomorphometric analysis revealed bone‐implant contact, as assessed by absolute bone contact (ABC) and contact length fraction (CLF). to be greater for the submerged design, suggesting that bone healing may be delayed with the non‐submerged approach. As well. at this early stage of healing, for both implant designs, ABC and CLF were significantly greater on proximal than on buccal and lingual aspects.     

EFFECTS OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE IV INHIBITOR, Ro20,1724, ON PANCREATIC EXOCRINE SECRETION IN DOG

1. The effects of the cyclic nucleotide phosphodiesterase (PDE) inhibitors, Ro20,1724, 3-isobutyl-1-methylxanthine (IBMX), trifluoperazine (TFP) and amrinone on pancreatic exocrine secretion were investigated in anaesthetized dogs in comparison with those of secretin and cholecystokinin octapeptide (CCK-8). 2. Ro20,1724 (1–30 nmol/kg), IBMX (3–30 nmol/kg), secretin (0.01–0.1 pmol/kg) or CCK-8 (0.1–1 pmol/kg) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but TFP and amrinone (up to 1 μmol/ kg) did not. 3. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by Ro20,1724, IBMX and secretin. Cholecystokinin octapeptide increased the protein concentration but did not alter the bicarbonate concentration. 4. Ro20,1724 and IBMX elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with Ro20,1724 and IBMX were additive. 5. Ro20,1724 and IBMX increased cyclic AMP concentration but did not affect cyclic GMP concentration. 6. These results suggest that Ro20,1724 and IBMX have secretory properties on pancreatic exocrine glands of the dog, which may be mediated through an increase in cyclic AMP subsequent to inhibition of PDE activity. Furthermore, pancreatic PDE enzymes in the dog may be mainly type IV.     

EFFECTS OF A SYNTHESIZED PHOSPHODIESTERASE INHIBITOR, ZSY-27, ON PANCREATIC EXOCRINE SECRETION OF THE DOG

The effects of a synthesized phosphodiesterase inhibitor, ZSY-27, on the secretion of pancreatic juice were investigated in dog isolated and blood-perfused pancreas, and compared with those of secretin and dopamine. Intravenous administration of ZSY-27 (0.3-1 mg/kg) elicited increases in pancreatic secretion. Intra-arterial (i.a.) administration of ZSY-27 (0.1-1 mg) also elicited increased secretion. The secretory activity of ZSY-27 (1 mg) was approximately equal to that of 0.1 units of secretin and 2.5 micrograms of dopamine. The concentration of bicarbonate in the pancreatic juice induced by ZSY-27 i.a. was increased, but the protein concentration was not increased significantly. These effects are analogous to those of secretin and dopamine. ZSY-27-induced pancreatic secretion was not modified by pretreatment with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced secretion was significantly potentiated by infusion of ZSY-27 (25 micrograms/min) but dopamine-induced one was not. These results suggest that ZSY-27 increases pancreatic secretion acting directly on the ductular cells of the dog pancreas, at least in part, through the increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.     

Effects of PEEP on extra vascular lung water and central blood volume in the dog

Twenty-four mongrel dogs were anaesthetized and ventilated mechanically in the supine position. Extravascular lung water (EVLW) and central blood volume (CBV) were measured with a double indicator (dye/cold) dilution technique. Both indicators were detected intravascularly in the aortic root with a fibreoptic thermistor catheter. Seven dogs ventilated with a positive end-expiratory pressure (PEEP) of 1.0 kPa (10 cmH2O) for a short period of time (less than 20 min) displayed no significant change in EVLW as measured with the indicator dilution technique (= EVLWi), while reductions were seen in both CBV (15%, P less than 0.01) and cardiac output (CO-thermodilution technique) (10%, P less than 0.05). Another seven dogs ventilated with a PEEP of 1.0 kPa for 8 h showed a gradual increase in EVLWi. After 8 h, a mean increase of 34% (P less than 0.01) was recorded, and the increase was also verified by post-mortem gravimetric determination of EVLW (= EVLWg), displaying an increase of 61% (P less than 0.01). In five dogs ventilated with zero end-expiratory pressure (ZEEP) for 8 h, no changes in EVLWi, CO, and CBV were observed, and EVLWg was mean 4.39 g/kg body weight (BW). Five additional dogs were sacrificed after 15 min of anaesthesia without catheterization and EVLWg was found to be 4.24 g/kg BW. It is concluded that EVLWi does not change measurably during ZEEP or short periods of PEEP. However, long periods (8 h) of PEEP result in elevated EVLWi values. Gravimetry supports these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

压力调节容量控制通气对肺损伤犬血流动力学、呼吸力学和呼吸功能的影响

目的 探讨压力调节容量控制(PRVC)通气模式对健康及急性肺损伤(ALI)模型犬的血流动力学、呼吸力学和呼吸功能的影响。方法 PRVC和间歇正压通气(IPPV)两种通气模式在呼气末压为0、0．5、1．0和1．5kPa时，分别测定健康犬及油酸诱发ALI犬的血流动力学、呼吸力学及血气参数。结果 健康犬PRVC较IPPV模式下除了在PEEP为0．5kPa时，气道峰压(PIP)、肺动态顺应性(Cdyn)和肺血管阻力(PVR)的影响差异有显著性，对血流动力学、呼吸力学及呼吸功能的影响差异均无显著性。ALI犬PRVC较IPPV模式下各PEEP水平的PIP、平均气道压(mPaw)、Cdyn、动脉血氧分压[pa(O2)]和氧耗(VO2)的影响均有显著意义，但两种通气模式对血流动力学的影响差异无显著性。结论 与IPPV相比，PRVC通气模式能降低PIP，增加Cdyn和提高pa(O2)，两模式对血流动力学的影响差异无显著性，PRVC更适用于ALI／ARDS的治疗。