Relation between the expression of vascular endothelial growth factor in synovial tissues and the extent of joint effusion seen on magnetic resonance imaging in patients with internal derangement of the temporomandibular joint.

The aim of this study is to elucidate the relation between the expression of vascular endothelial growth factor (VEGF) in synovial tissues and the extent of joint effusion seen on magnetic resonance imaging (MRI) in patients with internal derangement of the temporomandibular joint (TMJ). Using an immunohistochemical technique, we examined specimens of synovial tissues from 41 joints in 40 patients with internal derangement. Specimens from 36 of the 41 joints stained for VEGF. There was a significant correlation between the percentage of the VEGF-stained cells and the grade of joint effusion seen on MRI (P=0.0002, r=0.62). The correlation between the two was also significant on multiple logistic regression analysis (P=0.003, odds ratio=1.75). These results suggest that VEGF may have an important role in the genesis of joint effusion.

Expression of interleukin 6 in synovial tissues in patients with internal derangement of the temporomandibular joint.

Using an immunohistochemical technique, we examined synovial tissue from 46 temporomandibular joints (TMJ) with internal derangement in 44 patients. As controls, we examined synovial tissue specimens from 7 joints with habitual dislocation without pain. In synovial tissues from 21 of the 46 joints with internal derangement, interleukin 6 (IL-6) was expressed in the synovial lining cells and in the mononuclear cells infiltrating the periphery of the blood vessels. The density of IL-6-stained cells in specimens with internal derangement correlated significantly with the grade of joint effusion shown by magnetic resonance imaging (P=0.01, r=0.32).

SDZ ENA 713 facilitates central cholinergic function and ameliorates spatial memory impairment in rats.

We have clarified the effects of SDZ ENA 713 (ENA), a new phenyl-carbamate derivative, on the spatial learning impairment and neurochemical indices of central cholinergic neurons in rats. Basal forebrain (BF) lesioning with ibotenic acid markedly impaired acquisition ability in the water maze task without changing swimming rates and decreased choline acetyltransferase (ChAT) activity in the frontal cortex of rats. ENA (0.1, 0.2 mg/kg, p.o.) significantly ameliorated the impairment in acquisition ability in a dose-dependent manner. At 0.2 mg/kg, ENA prevented the reduction in ChAT activity. In normal rats, ENA (1 mg/kg, p.o.) increased extracellular ACh concentration of the prefrontal cortex. On the other hand, tissue concentrations of norepinephrine, serotonin, dopamine and their metabolites were not changed in the frontal cortex, hippocampus and striatum of normal rats. These results suggest that ENA ameliorates spatial learning disability by not only facilitating the cholinergic transmission, but normalizing impaired ChAT activity in the learning-impaired rat model.

Effects of continual intravenous posttreatment with D-CPP-ene, a potent competitive N-methyl-D-aspartate receptor antagonist, on rat brain edema induced by injection of triethyltin into the cerebral hemisphere.

Brain edema was produced by injecting triethyltin (TET) into the right cerebral hemisphere via the internal carotid artery in rats. TET induced a dose-related increase in mortality rate and brain water content. Immediately after TET-injection (2 mg/head), saline, glycerol (125 mg/ml) or the N-methyl-D-aspartate receptor antagonist (R)-4-(3-Phosphono-2-propenyl)-2-piperazine carboxylic acid (D-CPP-ene; 0.083 and 0.25 mg/ml) was continually infused via the right internal jugular vein at 20 microliters/min for 6 h. The mortality rate and brain water content were significantly decreased after infusion of 0.25 mg/ml D-CPP-ene, but only somewhat reduced after glycerol infusion when compared with the saline group. The results suggest that continual intravenous posttreatment with D-CPP-ene is useful for treatment of brain edema.

A cerebral ischemia model produced by injection of microspheres via the external carotid artery in freely moving rats.

We produced an improved microembolism model of cerebral focal ischemia by injection of 1000-2000 microspheres (50 +/- 5 microns diameter) via a tube retrogradely inserted into the right external carotid artery in freely moving rats. The group injected with 2000 spheres showed a much more severe mortality rate as well as neurological signs than did the 1000-sphere group. Brain water content of the 2000-sphere group was examined and found to show an increase from 4 to 24 h after embolization in the right hemisphere, indicating serious brain edema. Severe neurological signs and individual deaths by embolization were most likely related to the extent of development of brain edema. Examination of learning behavior by shuttle-box avoidance revealed partial but significant impairment of learning in the 1000-sphere group. Autoradiographic studies for muscarinic acetylcholine receptors and protein kinase C binding sites were conducted. Both these binding sites decreased in number, but protein kinase C seems to be more susceptible to ischemic injury than muscarinic acetylcholine receptors. The observation was considered to be closely related with an impairment of learning. The present study suggests that our microembolism model in freely moving rats is useful for investigations of the early phase and late phase of cerebral ischemia.

[Pharmacological comparison of the CNS effects of propentofylline and caffeine].

The CNS effects of propentofylline and caffeine, methylxanthine derivatives, were compared. In mice, caffeine antagonized diazepam-induced muscle relaxation and the inhibitory effect of diazepam against pentylenetetrazole-induced convulsions, but propentofylline did not. In spinal cats, the dorsal root reflex potentials were inhibited by caffeine but not affected by propentofylline, and the monosynaptic reflex potentials were increased by propentofylline but not influenced by caffeine. The results indicate that propentofylline differs from caffeine in that it neither antagonizes diazepam nor affects the GABA system.

Effects of propentofylline on disorder of learning and memory in rodents.

Effects of a newly synthesized xanthine derivative propentofylline (3,7-dihydro-3-methyl-1-(5-oxohexyl)-7-propyl-1H-purine-2,6-dione) on learning and memory of rodents were examined in the two different paradigms. In a shuttle box active avoidance paradigm, propentofylline (25 mg/kg/day, p.o.) improved the decreased learning ability of 12-month-old spontaneously hypertensive rats. Normotensive Wistar-Kyoto rats at a comparable age showed rapid acquisition of avoidance learning, which was not influenced by propentofylline. Step-down passive avoidance task was carried out as the other paradigm. The protein synthesis inhibitor cycloheximide (CXM) induced amnesia in young adult mice. Propentofylline improved the memory deficit when intraperitoneally administered 30 min before the retention test, and it also prevented the development of amnesia when injected 15 min before CXM. These results suggest that propentofylline ameliorates the disturbed learning and memory.

Role of extracellular calcium and calcium efflux in the activation of hepatic glycogenolysis by calcium-dependent hormones.

The role of extracellular calcium in the glycogenolytic effects of calcium-dependent hormones was examined in a rat liver perfusion system. Decreasing the perfusate CaCl2 concentration resulted in a concentration-dependent inhibition of glucose output by maximal concentrations of vasopressin (20 nM) and angiotensin II (10 nM), but not of glucagon (1.4 nM), cyclic AMP (100 microM), dibutyryl cyclic AMP (10 microM) or phenylephrine (5 microM). However, the effect of phenylephrine was inhibited when livers were perfused with CaCl2-free perfusate containing 0.5 mM EGTA in a duration-dependent manner. These effects were exerted through the inhibition of the maximal response of each hormone, and were associated with a parallel decrease in phosphorylase activation but not with changes in tissue cyclic AMP concentrations. When livers were preloaded with 45Ca for 45 min and then washed for either 15 min or 45 min, these hormones elicited a rapid and transient 45Ca efflux regardless of the perfusate calcium concentration. The sequential perfusion of two hormones resulted in the loss of 45Ca efflux by the second hormone. These results suggest that the glycogenolytic effects of vasopressin and angiotensin II depend on the extracellular calcium and that of phenylephrine primarily on the cellular calcium. It was also demonstrated that these calcium-dependent hormones mobilize calcium from the same pools. However, the mobilization of cellular calcium does not necessarily correlate directly with the glycogenolytic actions of vasopressin and angiotensin II.

Difference in the mechanism of action of alpha-adrenergic agonists and vasopressin or angiotensin II in stimulating hepatic glycogenolysis; a role of extracellular calcium concentration.

The role of extracellular calcium in hormone-induced glycogenolysis was examined in a rat liver perfusion system by manipulating the perfusate calcium concentration and by using calcium antagonistic drugs. When the perfusate contained 1 mM CaCl2, 5 microM phenylephrine, 20 nM vasopressin, and 10 nM angiotensin II caused a persistent increase in glucose output and phosphorylase activity as well as a transient increase in 45Ca efflux from 45Ca preloaded liver. Verapamil hydrochloride (20-100 microM) inhibited the activation of glucose output by these hormones in a dose-dependent manner. This inhibitory effect was also associated with the inhibition of hormone-induced activation of phosphorylase and 45Ca efflux. In the absence of CaCl2 in the perfusate, the glycogenolytic effect of phenylephrine and its inhibition by verapamil were obtained equally as in the presence of CaCl2. However, the effects of vasopressin and angiotensin II were markedly attenuated and were not inhibited any further by verapamil. The substitution of diltiazem hydrochloride for verapamil produced essentially identical results. Cyclic AMP concentrations in the tissue did not change under any of these test conditions. The results indicate that the glycogenolytic effect of alpha-adrenergic agonists depends on intracellular calcium but those of vasopressin and angiotensin II on extracellular calcium, and support the concept that calcium antagonistic drugs inhibit the glycogenolytic effects of calcium-dependent hormones at least by inhibiting the mobilization of calcium ion from cellular pools.