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The aim of this study was to investigate the effect of A-3922, a dihydrobenzofuran derivative, on linoleic acid hydroperoxide (LHP)-induced corneal neovascularization (NV) in a rabbit model. Male New Zealand rabbits Received intraperitoneal (i.p.) injections of 10 or 30 mg/kg per day A-3922 or its vehicle as control for 3 days. One day after i.p. injections, LHP was injected with a 30-gauge needle into the corneal stroma of the superior quadrant 4.5-mm below the limbus. Photographs of the vessels were taken for digital analysis with a surgical microscope. Vascular endothelial growth factor (VEGF) was measured using an immunoassay kit, and matrix metalloproteinase (MMP)-9 was measured by gelatin zymography in corneal samples. At 7 days post-LHP injection, the total vessel length was 26.7 ± 3.8 mm in the control animals (n = 8), 16.1 ± 0.8 mm in the A-3922 (10 mg/kg)-treated group (n = 5), and 11.4 ± 2.1 mm in the 30 mg/kg group (n = 8, P

The effects of formaldehyde (F), m-cresol (C), guaiacol (G), ethanol (E) and their mixture (FC, FCE, FG, FGE) on erythrocytes and isolated hepatocytes from rats and surface tension in water were examined. Hypotonic hemolysis of erythrocytes was inhibited by m-cresol, while guaiacol, formaldehyde and ethanol accelerated the hemolysis. Lower concentrations of the mixture inhibited hypotonic hemolysis, but higher concentrations accelerated hemolysis. Formaldehyde caused a decrease of transaminase (GOT, GPT) in the medium and hepatocytes. GOT and GPT in the medium were increased by m-cresol, but those in the hepatocyte were decreased by this agent. FC and FCE at 10 mM increased GOT in the medium, but FG and FGE decreased GOT. All mixtures decreased GOT and GPT in hepatocytes and GPT in the medium. All mixtures and formaldehyde inhibited GOT and GPT activity. Formaldehyde and m-cresol decreased hepatocyte viability. In the all mixtures-added hepatocytes, the viability was markedly lowered. Formaldehyde, m-cresol, guaiacol and ethanol caused a depression of surface tension, but the depressive effects of FG and FGE were weaker than that of guaiacol. These results suggest that the observed effects of the drug mixtures on erythrocytes and hepatocytes were the additive effects of the component drugs.

The effects of hot water extracts (HWEs) from 15 kinds of Compositae herbs and distanninized fractions (DTFs) from 9 of these herbs on rat hepatic lipid peroxidation (LPO) and the activities of aminopyrine N-demethylase (APD) and aniline hydroxylase (ANH) were examined in vitro. The APD activity was inhibited by HWEs from 12 herbs, of which the effect of HWE from Inchinko was remarkable. Inhibitory effects of DTFs from Inchinko, Gaiyo, Kantoka, Sojustu and Byakujutsu on the APD activity were smaller, if any, than those of the corresponding HWEs, whereas DTF from Koka enhanced the activity of APD. The ANH activity was inhibited by HWEs from 11 herbs. HWEs from Inchinko, Gaiyo and Senpukuka increased the ANH activity, whereas the DTFs from them caused inhibition. The inhibitory effect of DTF from Shion on the ANH activity was smaller than that of the corresponding HWE, but the effects of DTFs from Koka, Byakujutsu, Sojutsu and Mokko were larger than those of the respective HWEs. LPO was inhibited by HWEs from 14 herbs, of which the HWEs from Inchinko, Gaiyo, Kantoka, Koka and Mokko caused marked inhibitions. Except in the case of Shion, the inhibitory effects of DTFs on LPO were smaller than those of the corresponding HWEs, whereas DTF from Koka still showed a marked inhibition. In the present experiments, it is suggested that Inchinko, Gaiyo, Koka, Kikuka, Senpukuka, Byakujutsu, Sojutsu and Mokko, which showed remarkable effects on LPO and the activities of APD and ANH, might also exert their effects in vivo.

The anti-atherogenic effect of NIP-200 3,5-dimethyl-4,6-diphenyl-tetrahydro-2H-1,3,5-thiadiazine-2-thione ) was studied in experimental models of 1% cholesterol diet (HCD)-fed rabbits. Interference with growth of the animals did not occur in NIP-200-treated rabbits. NIP-200 had no effect on plasma total cholesterol (TC), triglyceride, free cholesterol and phospholipid during the entire experimental period. However, NIP-200 increased high density lipoprotein-cholesterol (HDL-C) at 1, 2, 4 and 6 weeks, although the average rate of increase was not statistically significant. Percentage surface areas of atherosclerotic lesions on the aorta in NIP-200-treated rabbits (26 +/- 6%) was significantly lower than those in HCD-fed rabbits (48 +/- 8%) (P less than 0.05). Histological studies indicated that NIP-200 prevented intimal thickening, proliferation of elastic fibers and fatty necrosis. Thus, NIP-200 prevented the progression of atherosclerosis without affecting the serum TC. The above results suggest that the improvement of lipoprotein metabolism on the arterial wall and the prevention of migration and proliferation of arterial smooth muscle cells may also be important factors in the progression of atherosclerosis.

Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration were investigated. We confirmed that reverse tolerance in stereotyped behavior was constructed up to the 28th day after repeated intermittent pretreatment with increasing doses of MAP (2.5, 5, and 7.5 mg/kg x 3 and 10 mg/kg x 2, every other day). During acoustic stimulation, locomotor activity in the saline group was significantly increased, but the activity after the stimulation was completely suppressed. In contrast to the saline group, locomotor activity was not influenced by the acoustic stimulation in the MAP group, suggesting that behavioral hyporesponsiveness to acoustic stimulation was induced by MAP treatment. Two days after the last injection, the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyphenylacetic acid (5-HIAA) in the cerebral cortex, midbrain + thalamus, hypothalamus and striatum were significantly decreased. These changes were maintained up to the 28th day after the drug withdrawal in the cerebral cortex and the midbrain + thalamus. From these results, the persistence of behavioral hyporesponsiveness to acoustic stimulation might be associated with long-lasting reduction of 5-HT synthesis.

The effect of human placenta hydrolysate (Laennec) on residual liver regeneration after about 70% partial hepatectomy (PH) in normal and CCl4-induced cirrhosis rats was examined. Both intravenous or subcutaneous injections of Laennec increased the regeneration rate of the residual liver after PH in normal rats. Intravenous injection of Laennec inhibited the decrease of liver total protein, and it decreased the level of serum transaminase (GOT, GPT). The regeneration rate of the residual liver after PH in CCl4-induced cirrhosis (CCl4-PH) rats increased by intravenous or subcutaneous injection of Laennec. Laennec also inhibited the increase of serum GOT caused by CCl4-PH. In the pathological examination of the regenerating liver, intravenous injection of Laennec minimized the pathological changes caused by PH or CCl4-PH such as vacuolation and necrosis in the hepatocytes. The enhancement of cytoplasma regeneration in hepatocytes was noticed by intravenous injection of Laennec, but that by subcutaneous Laennec was slight. Intravenous injection of Laennec also minimized the lipid deposition in liver caused by CCl4-PH. Laennec had no effect on the pseudolobule formation caused by CCl4. Thus, the effect of intravenous injection of Laennec on the liver regeneration in PH rats was much more potent than that by the subcutaneous injection.