[Correlation of semiquantitative analysis of the distribution of pulmonary perfusion with pulmonary function in chronic obstructive pulmonary disease].

We carried out ventilation-perfusion scintigraphy and pulmonary function tests in 56 patients with chronic obstructive pulmonary disease (COPD) and 19 healthy volunteers. We used 99mTc-macroaggregated albumin for the perfusion scintigraphy and 33Xe gas for the ventilation scintigraphy. The lung volume image was created by computerized summation of the radioactivity in the rebreathing phase. Regions of interest (ROIs) were set automatically on lung volume image, which included each whole lung, and on perfusion image, including areas with relatively high radioactivity, with cut-off levels of 50%, 70%, and 90%. The number of pixels in each RO1 was used as an index of lung volume (L) or perfusion (P). Perfusion per unit of lung volume (P/L) was also used as an index of perfusion. P70 and P70/L showed the better correlations than the other parameters, including significant correlations with vital capacity, FEV1.0, peak flow rate, RV/ TLC, diffusing capacity and arterial oxygen partial pressure. The significant difference in P70 and P70/L between patients with hypoxemia and those without hypoxemia suggested that P70 and P70/L are useful indicators of the severity of COPD. We conclude that semiquantified values of pulmonary perfusion scintigraphy are significantly correlated with pulmonary function and the severity of COPD.

[Evaluation of pontine visualization with single photon emission computed tomography using N-isopropyl-p-(I-123)iodoamphetamine in normal and pathological cases].

Pontine visualization with single photon emission computed tomography (SPECT) using N-isopropyl-p-[I-123]iodoamphetamine (I-123 IMP) was evaluated in 99 cases including 46 cases of brain infarction, 25 of other cerebrovascular disorders and 28 of brain tumor and in 19 normal subjects. In each case, SPECT using a rotating gamma camera was started at 30 minutes after intravenous administration of 111 MBq of I-123 IMP. Transverse images were reconstructed parallel to the cantho-meatal line and displayed on films. Pontine visualization was visually classified into three grades: high radioactive accumulation confined to the pons with clear contour (Grade 3), faint accumulation with indistinct contour in the pontine region (Grade 1), the pontine accumulation was identified but its activity was less significant (Grade 2). The results showed that grade of the pontine accumulation was lower in pathological cases compared to normal subjects. Six cases with brain stem lesion demonstrated pontine accumulation of grade 1 in 4 case and of grade 2 in 2 cases. Lower grade was also revealed in 29 cases with crossed cerebellar diaschisis (CCD). No significant correlation was observed between classified grade of pontine accumulation and maximum counts of reconstructed images. We concluded that SPECT could detect brain stem lesions and that lower accumulation in pons with CCD positive cases was thought to partially reflect the reduced blood flow and metabolism in the pontine nuclei.

Comparison of the calcium entry and calcium overload blocking properties of R71811 and flunarizine.

The effects of several calcium antagonists on cell death induced by A23187 were studied. Furthermore, R71811, 1-[Bis(4-fluorophenyl)methyl-4-[(4-methoxyphenyl)- carbamoylmethyl-trans-2,5-dimethyl-piperazine has been evaluated as a calcium overload blocker and compared to flunarizine. The viability of cultured glial cells was decreased by incubation with the calcium ionophore, A23187. The cytotoxicity of A23187 was reduced by flunarizine and cinnarizine at 10 mumol/l; nicardipine, nifedipine, and verapamil, but not diltiazem, reduced cytotoxicity at 100 mumol/l. N-(6-aminohexyl)-5-chloro-1- naphthalenesulfonamide (W-7) and trifluoperazine did not reduce cytotoxicity and trifluoperazine enhanced cytotoxicity at 100 mumol/l. Leupeptin reduced cytotoxicity at 100 mumol/l. [8-(N,N-dimethylamino)-octyl-3,4,5- trimethoxybenzoate] (TMB-8) showed no effect. The results indicate that flunarizine, a recognized calcium overload blocker, was most effective in inhibiting the A23187-induced cytotoxicity and that calcium entry blockade does not appear to be implicated in the cytoprotective effect. R71811 inhibited A23187 cytotoxicity at similar concentrations to flunarizine. R71811, as well as flunarizine, also inhibited erythrocyte crenation induced by A23187. Although R71811 showed a relaxant effect in isolated rat aorta contracted by high potassium, its activity was less than that of flunarizine (IC50 values, 4.1 and 0.045 mumol/l, respectively). On the other hand, R71811 and flunarizine showed similar inhibitory effects on A23187-induced contractions (IC50 values, 14 and 11 mumol/l, respectively). The results indicate that R71811 has a similar protective effect against A23187-induced cytotoxicity but only weak calcium entry blocking action in comparison to flunarizine.

[A case of subacute cerebral infarction demonstrating hyperemia and crossed cerebellar diaschisis in I-123 IMP SPECT].

SPECT with N-isopropyl-p-[I-123]iodoamphetamine were performed in a 81-year-old man with cerebral infarction. In the subacute phase, the radioactivity was increased in the infarct area where fogging effect and remarkable contrast enhancement was demonstrated in X-ray CT. The contralateral cerebellar hemisphere showed reduced activity due to crossed cerebellar diaschisis (CCD). In the chronic phase, the decrement of the activity in the infarct was observed. Increased activity in the subacute phase was thought to reflect the hyperemia in the infarct, while CCD suggested the decreased metabolic activity in the lesion. The coexistence of the hyperemia and the CCD indicates flow and metabolic uncoupling, which means "luxury perfusion". This case was also thought to demonstrate atypical findings of CCD in SPECT imaging.

S-adenosyl-L-methionine improves the changes of calcium content and glucose metabolism after transient ischemia in the rat.

Effects of S-adenosyl-L-methionine on Ca accumulation as well as the changes of electrolytes contents and glucose metabolism after transient ischemia were investigated. In the 4-vessel occlusion model of rats, brain Ca content increased to 200-250% of that in sham operated rats 1 day after 60 min transient ischemia. The change in the striatum was more severe than that in the cortex or hippocampus. Na content increased and K content decreased, and glucose, pyruvate and lactate contents increased significantly in the striatum 1 day after transient ischemia. SAM (100 mg/kg, i.p.) was injected at the end of occlusion and every hour for 5 hr thereafter. Treatment with SAM reduced Ca accumulation, decrease of K, and increase of lactate and pyruvate in the striatum significantly. The present results suggest that the inhibition of Ca accumulation might partly explain the beneficial effects of SAM on the cerebral dysfunction following ischemia.

[Pharmacological studies on diuretics (8). Diuretic activity and mechanism of action of a new hypotensive diuretic, SE-1520 (author's transl)].

Effects of SE-1520 were compared with those of thiazide diuretics, hydrochlorothiazide (HCT) and trichlormethiazide (TCM) in rats and dogs. SE-1520 in an oral dose of 0.1 approximately 10.0 mg/kg resulted in a strong and dose-dependent increase in urine volume as well as in the urinary excretion of Na+ and Cl-, while that of K+ significantly increased with an oral dose over 3.0 mg/kg. In experimental acidotic, alkalotic, nephritic and spontaneously hypertensive rats, almost the same strong natriuretic activity seen in normal rats was observed with SE-1520. The diuretic potency of these three diuretics in rats was MCT greater than or equal to SE-1520 greater than HCT. SE-1520 also exhibited a strong diuretic activity in dogs. In the renal clearance test of dogs, SE-1520 0.1 approximately 1.0 mg/kg i.v. did not influence the renal plasma flow (RPF) or glomerular filtration rate (GFR). The renal tubular Na+ reabsorption rate decreased by a maximum of 2.11% and the urinary Na+ excretion increased by 15.3 times the normal level 20 min after the injection of SE-1520 in a dose of 1.0 mg/kg i.v. From the results of clearance test and stop flow test in dogs, the site of action of SE-1520 was observed to be mainly in the distal tubules.

Anti-ulcer effects of 4'-(2-carboxyetyl) phenyl trans-4-aminomethyl cyclohexanecarboxylate hydrochloride (cetraxate) on various experimental gastric ulcers in rats.

Anti-ulcer effects of cetraxate, a new compound possessing anti-plasmin, anti-casein and anti-trypsin actions were investigated by using experimental gastric ulcer models in rats. Cetraxate, 300 mg/kg p.o. showed significant inhibitory effects of 65.3%, 70.0%, 30.2%, and 67.1% against aucte types of ulcers producing by aspirin, phenylbutazone, indomethacin, and pyloric ligature (Shay's ulcer), respectively. These effects were greater than those obtained by gefarnate and aluminum sucrose sulfate may be mainly attributed to the protecting action of this drug on gastric mucosa. Ctraxate further revealed remarkable inhibitory effects on chronic types of ulcers produced by acetic acid, clamping, and clamping-cortisone. In acetic acid ulcer in particular, cetraxate was found to have a dose-dependent inhibitory effect at doses over 50 mg/kg. Of test drugs including L-glutamine and methylmethionine sulfonium chloride, cetraxate showed the most remarkable inhibitory effect on beta-glucuronidase activity in ulcer tissue of these three types of ulcers. These findings suggest that cetraxate may prevent the connective tissue in the ulcer location from decomposition due to lysosomal enzymes such as beta-glucuronidase, thereby accelerating the recovery from ulcer.

Mechanism of action of a new anti-inflammatory agent, naproxen (II). Effects of naproxen on activities of mucopolysaccharase, acid protease and collagenolytic enzymes in inflamed tissues.

In order to elucidate the biochemical anti-inflammatory properties of naproxen, the effects of this compound on activities of mucopolysaccharase [beta-glucuronidase (beta-Gase) and lysozyme (LZ)], acid protease (APase) and collagenolytic enzyme (CL) in inflamed tissues were investigated by means of a proliferative inflammatory model in filter-paper-implanted rats. In the preventive test, naproxen strongly inhibited granuloma formation and exudate accumulation as did indomethacin and prednisolone. Although the inhibitory effects of naproxen on all these enzymes were quite evident, indomethacin failed to inhibit APase activity. Prednisolone did not significantly inhibit LZ and APase activities in granuloma. In the curative test, prednisolone caused a marked decrease in the weight of the granuloma already formed and in the volume of the exudate, but with naproxen and indomethacin there was only a slight decrease. Naproxen and indomethacin induced slight but significant inhibition of LZ and CL activities, while prednisolone showing a weak inhibition of CL activity only. From these results, it may be concluded that anti-inflammatory and anti-rheumatic effects of naproxen are partly attributable to its inhibitory actions on these lysosomal enzymes.