Periradicular healing in response to Diaket root-end filling material with and without tricalcium phosphate

The healing of the periradicular tissues was evaluated when the polyvinyl resin Diaket with and without tricalcium phosphate was used as surgical root-end filling material. Non-surgical root canal treatment was performed on 56 mandibular premolar roots in mongrel dogs. Following root-end resection, root-end cavity preparations were filled with Diaket, the comparative material, or Diaket in combination with tricalcium phosphate, the experimental material. Postsurgically, healing of the tissues adjacent to the filling materials and in the surrounding surgical site were evaluated at 30 and 60 days. There was virtually no statistically significant difference between the experimental and comparative group at or within the 30- or 60-day period with regard to inflammation, connective tissue formation, root-end encapsulation, cementum formation, or bone apposition. Findings suggest that cementogenesis occurred over both materials. The overall healing of the periradicular tissues was favourable.     

EFFECT OF CROSS-FOSTERING ON NEONATAL SODIUM BALANCE AND ADULT BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams’ milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 ± 2.0 to 15.2 ± 1.2 mmol/L; SHR 31.9 ± 2.5 to 18.2 ± 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P< 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P<0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4–15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 ± 3.6 vs 59.7 ± 2.6 μmol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 ± 7.0 μmol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 ± 6.4 vs 200.1 ± 9.5p, mol/g bodyweight, respectively; P<0.05) or SHRX pups (200.0 ± 18.0 μmol/g bodyweight; P<0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure.     

DIFFERENCES IN ENDOTHELIUM-DEPENDENT RELAXATION IN VARIOUS ARTERIES FROM WATANABE HERITABLE HYPERLIPIDAEMIC RABBITS WITH INCREASING AGE

1. Endothelium-dependent relaxation in response to acetylcholine (ACh) and the calcium ionophore A 23187 was examined in aorta, coronary, basilar and renal arteries isolated from Watanabe heritable hyperlipidaemic (WHHL) rabbits of 2, 6 and 12 months of age, with normolipidaemic heterozygous WHHL rabbits as controls. 2. In the rings of WHHL rabbit aortae and coronary arteries preconstricted with vasoconstrictors, endothelium-dependent relaxation in response to ACh was attenuated with age compared to the heterozygous WHHL rabbits. A significant negative correlation was found between the total cholesterol content and the relaxation response to ACh in the aortae or coronary arteries from 6 and 12 month old WHHL rabbits. 3. In the rings of basilar arteries, endothelium-dependent relaxations to ACh were not modified with age. Similarly, in the rings of renal arteries, the relaxation response to ACh was not changed with age, but in the 6 and 12 month preparations, after the age of 6 months, a contraction following the relaxation appeared at higher concentrations of ACh (10^?7 to 10^?6 mol/L). The contraction was endothelium-dependent and inhibited by indomethacin. 4. A 23187-induced endothelium-dependent relaxations were also markedly attenuated in the aorta and significantly in the coronary artery with age. 5. Endothelium-independent relaxation to sodium nitroprusside was not changed in all arteries from WHHL rabbits of different ages. 6. These findings indicate that in the aorta and coronary artery of the WHHL rabbit, the endothelium-dependent relaxation to ACh and A 23187 becomes impaired with increasing age (i.e., with the progression of cholesterol deposition in the arterial wall) but is preserved in the basilar and renal artery.     

Na+ currents near and away from endplates on human fast and slow twitch muscle fibers

Fast and slow twitch muscle fibers have distinct contractile properties. Here we determined that membrane excitability also varies with fiber type. Na⁺ currents (I_NA) were studied with the loose-patch voltage clamp technique on 29 histochemically classified human intercostal skeletal muscle fibers at the endplate border and <200 μm from the endplate (extrajunctional). Fast and slow twitch fibers showed slow inactivation of endplate border and extrajunctional I_NA and had increased I_NA at the endplate border compared to extrajunctional membrane. The voltage dependencies of I_NA were similar on the endplate border and extrajunctional membrane, which suggests thatboth regions have physiclogically similar channels. Fast twitch fibers had larger I_NA on the endplate border and extrajunctional membrane and manifest fast and slow inactivation of I_NA at more negative potentials than slow twitch fibers. For normal muscle, the differences between I_NA on fast and slow twitch fibers might: (1) enable fast twitch fibers to operate at high firing frequencies for brief periods; and (2) enable slow twitch fibers to operate at low firing frequencies for prolonged times. Disorders of skeletal membrane excitability, such as the periodic paralyses and myotonias, may impact fast and slow twitch fibers differently due to the distinctive Na⁺ channel properties of each fiber type. © 1993 John Wiley & Sons, Inc.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.     

Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate

Summary Prophylactic treatment with alkaline citrate in patients with recurrent calcium oxalate (CaOx) stone disease results in reduced CaOx supersaturation and increased urinary citrate. The effects of a single evening dose were compared with those of two and three daily doses in six recurrent CaOx stone formers with hypercalciuria, hypocitraturia or raised calcium/citrate quotients. While on a standardized hospital diet the patients were given 7.5 g (28 mmol) of sodium potassium citrate (URALYT-U) in one, two, and three doses. Fractional urine collections during 24 hours were analyzed for pH, composition, and crystallization risk (CR). All dosage regimens had favourable effects on urinary calcium, citrate, calcium/citrate quotients, and CaOx-CR. The most sustained effect was recorded with three divided doses. Single evening doses resulted in the most pronounced effects between 22.00–06.00 h, thereby counteracting the increased risk of CaOx crystallization during that period. In terms of 24 h urine composition the best effect was recorded with alkaline citrate administered three times daily, but because of the favourable response by a single evening dose between 22.00–06.00 h the assumption was made that this dosage regimen might be sufficient to reduce the risk of CaOx crystallization and stone formation. However, the validity of such an assumption can only be established by long-term clinical studies.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

钠摄入量对心力衰竭大鼠心脏肾素-血管紧张素系统与心钠素的影响

目的　观察钠摄入量对心力衰竭大鼠心脏局部肾素-血管紧张素系统与心钠素的影响 .方法　经动 -静脉分流术造成大鼠充血性心衰模型 ,分为心衰组、心衰限钠组、心衰补钠组 ,假手术大鼠为对照组 ,用放射免疫分析法和原位杂交技术分别测定各组血浆和心肌血管紧张素 、心钠素含量及心肌血管紧张素原 m RNA表达水平 (吸光度 A值 ) ,同时检测心功能 .结果　心衰限钠组心房和心室血管紧张素 含量(2 0 .1± 4 .5 )和 (2 7.3± 5 .9) ng· g- 1、血管紧张素原 m RNA表达 (6 .4± 1.2 )和 (12 .6± 2 .3)显著高于心衰组 (17.5± 3.6 )和 (2 0 .1± 3.7) ng· g- 1 ,(6 .2± 1.9)和 (8.6± 1.7) (P<0 .0 5 ,P<0 .0 1) ,心室心钠素 (42 3± 6 8) ng· g- 1 也显著高于心衰组 (337± 86 ) ng· g- 1 (P<0 .0 5 ) ,心房心钠素 (6 7± 19)μg· g- 1显著低于心衰组 (85± 15 ) μg· g- 1 (P<0 .0 5 ) ;心衰补钠组心房和心室血管紧张素原 m RNA表达水平、心室血管紧张素 和心钠素与心衰组无显著差别 ,心房血管紧张素 与对照组无显著差别 ,心房心钠素 (10 1± 17) μg· g- 1 显著高于心衰组 (P<0 .0 1) .结论　心衰时不同钠摄入量可通过改变心脏局部肾素 -血管紧张素系统与心钠素的平衡状态在心衰发展进程中发挥作用     

Zero-Order Release Formulation of Oxprenolol Hydrochloride with Swelling and Erosion Control

Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower C _max, higher values of t _max, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.