The effect of sho-saiko-to on concentration of vitamin E in serum and on granuloma formation in carrageenin cotton pellet-induced granuloma rats.

The effect of Sho-saiko-to on the concentration of vitamin E in serum and on the granuloma formation in Carrageenin cotton pellet-induced rats was investigated. As a result, in the granuloma rats of Sho-saiko-to group, a significantly improved inhibitory effect on granuloma formation and a higher concentration of vitamin E in serum, cholesterol and phospholipid were observed compared to the control group. Despite this lipid-increasing action by Sho-saiko-to, the concentration of serum lipid peroxide was significantly lower than in the control group. Furthermore, a significant negative correlation between the concentration of vitamin E and granuloma weight was observed. These results suggest that vitamin E plays an important role in promoting the anti-inflammatory effect of Sho-saiko-to.

Analgesic effect of Ga-Al-As diode laser irradiation on hyperalgesia in carrageenin-induced inflammation.

This study concerned the effect of Ga-Al-As diode laser irradiation (780 nm, continuous wave, 31.8 J/s/cm2, spot size od 0.2 mm, 3 minutes/dose) on hyperalgesia induced in the hind paw of rats by injecting carrageenin. The pressure-pain thresholds of hind paws were measured by the Randall-Selitto test for evaluation of hyperalgesia. Two doses of laser irradiation, given to the inflamed region immediately before and after the injection of carrageenin, partially (approximately 50%) inhibited the occurrence of hyperalgesia accompanied with a progression of inflammation. This analgesic effect was equal to that of indomethacin (4 mg/kg, i.o.). In another group, the hyperalgesia was removed almost completely for at least 24 hours by one dose of laser irradiation, which was given 3 hours after the carrageenin injection, whereas the edema was not inhibited. This analgesic effect, however, was partially (approximately 50%) antagonized with a dose of 10 mg/kg (i.p.) of naloxone and totally inhibited with 30 mg/kg. These results suggest that low-power laser irradiation on inflamed regions of carrageenin-treated rats has a marked analgesic effect and that certain mechanisms that are not related to endogenous opioids are involved in a part of the mechanisms of the analgesic effects.

The effect of orengedokuto on experimentally-inflamed rats.

The inhibitory effect of Orengedokuto on lipid peroxide and sialidase was investigated using rats affected with carrageenin cotton pellet-induced granuloma and adjuvant arthritis. As a result, in the case of rats with carrageenin cotton pellet-induced granuloma, a significant inhibitory effect on granuloma formation was observed in the Orengedokuto treated rats (150 mg/kg/day) which showed a decrease in serum lipid peroxide (p < 0.001) and an increase in acid soluble glycoprotein (p < 0.001). In the case of adjuvant-induced arthritic rats, however, the condition of the arthritis was not improved at all, and was even aggravated in spite of the decrease in serum lipid peroxide.

The effect of sho-saiko-to on the concentration of acid soluble glycoprotein in serum and on granuloma formation in carrageenin cotton pellet-induced granuloma rats.

The effect of sho-saiko-to on the concentration of acid soluble glycoprotein in serum and on the granuloma formation in carrageenin cotton pellet-induced rats was investigated. As a result, a significant negative correlation between the concentration of acid soluble glycoprotein and granuloma weight was observed. Furthermore, both the concentration of acid soluble glycoprotein and the inhibition rate of the granuloma formation were significantly higher in the sho-saiko-to group than in the control group. These results suggest that acid soluble glycoprotein plays an important role in promoting the anti-inflammatory effect of sho-saiko-to.

Effect of intrahypothalamic injection of neostigmine on the secretion of epinephrine and norepinephrine and on plasma glucose level.

We previously reported that the injection of neostigmine, an inhibitor of acetylcholinesterase, into the third cerebral ventricle of fasted rats produced hyperglycemia associated with the secretion of epinephrine and norepinephrine. However, the central nervous system site of action of neostigmine by which the plasma catecholamine and glucose concentrations were increased is not known. In this study we injected neostigmine into the ventromedial hypothalamus, lateral hypothalamus, paraventricular hypothalamus, median site of the lateral-preoptic area, lateral site of the lateral-preoptic area, anterior site of the anterior hypothalamic area, mammillary body (posterior mamillary nucleus), and cortex of anesthetized fasted rats and measured the plasma levels of glucose, epinephrine, and norepinephrine. It was found that the ventromedial hypothalamus, lateral hypothalamus, paraventricular hypothalamus, and median site of the lateral-preoptic area were involved in increasing the plasma levels of glucose and epinephrine. From this evidence we conclude that neostigmine acts on selected regions known to be involved in glucoregulation in the hypothalamus to increase the plasma levels of epinephrine and glucose.

Therapeutic effect of Ga-Al-As diode laser irradiation on experimentally induced inflammation in rats.

We produced experimental inflammation models in rats by carrageenin and studied the effect of Ga-Al-As diode laser irradiation (780 nm, continuous wave, 31.8 j/sec/cm2, spot size of 0.2 mm) on inflamed regions compared with those of indomethacin, a potent anti-inflammatory agent. We found that a low-power infrared laser has an anti-inflammatory effect on carrageenin inflammation. A low-power laser inhibits: (1) the increase of vascular permeability during the occurrence of an acute inflammation in the carrageenin-air-pouch model, (2) edema in the acute stage in the carrageenin-paw-edema model, and (3) the granuloma formation in the carrageenin-granuloma model after receiving laser irradiation once daily. In all cases, irradiation for less than 10 min was sufficient to inhibit the inflammation by 20-30%. The inhibitory effect of laser irradiation was not comparable to that of indomethacin (4 mg/kg, i.o.) in the air-pouch model and the paw-edema model, whereas laser irradiation was more potent than that of daily administration of indomethacin (1 mg/kg, i.o.) in the granuloma model. In future studies of the mechanism of laser effect, it should be noted that irradiating a rat twice, before and after the provocation of inflammation, was essential in order to achieve an effective inhibition of paw-edema.

Involvement of the hippocampus in central nervous system-mediated glucoregulation in rats.

To find out whether the hippocampus is involved in central nervous system-mediated glucoregulation, we injected saline, neostigmine, dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, and prostaglandin F2 alpha into the dorsal hippocampus in anesthetized fed rats. After injection of dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, or prostaglandin F2 alpha, the level of hepatic venous plasma glucose did not differ from that in saline-treated control rats. However, neostigmine, an inhibitor of acetylcholine esterase, caused a dose-dependent increase in the hepatic venous plasma glucose concentration. This neostigmine-induced hyperglycemia was dose-dependently suppressed by coadministration of atropine, but not by hexamethonium. Injection of neostigmine (5 X 10(-8) mol) resulted in an increase not only in glucose but also in glucagon, epinephrine, and norepinephrine in hepatic venous plasma. In bilateral adrenalectomized rats, neostigmine-induced hyperglycemia was suppressed, but the hepatic venous plasma glucose concentration still increased significantly. These results indicate that the hippocampus is involved in central nervous system-mediated glucoregulation through cholinergic muscarinic activation, partly via epinephrine secretion.

Influence of electrical stimulation of the limbic structure on adrenocortical steroidogenesis in hypophysectomized rats.

The effects of electrical stimulation of the medial amygdala (AMYG) and dorsal hippocampus (DHPC) on the rates of 14C transfer from 14C-1-acetate into adrenocortical steroids in adrenal slices of hypophysectomized rats were investigated. The 14C transfer rates into corticosterone were increased by stimulation of the AMYG and DHPC. The 14C transfer rates into cortisol were increased by the AMYG stimulation but were not altered by the DHPC stimulation. From these results, it might be suggested that these limbic structures were involved in the regulation of adrenocortical steroidogenesis without participation of the pituitary.

Nerve growth factor-mediated sexual differentiation of the rat hypothalamus.

Injection of antibody to nerve growth factor into the cerebral lateral ventricle blocked testosterone-induced behavioral defeminization of neonatal female rats. When tested as adults following ovariectomy and combined estrogen-progesterone treatment, the injected animals showed a significantly higher lordosis quotient than the testosterone-treated, normal rabbit serum-infused controls. Failure of vaginal opening and clitoral enlargement manifested the well-documented masculinizing effect of testosterone on the genitalia in the experimental as well as the control animals. Estrogen sensitivity of hypothalamic neurons which are responsible for the induction of lordosis was retained in the experimental animals. Recordings of the antidromic action potentials from neurons in the ventromedial nucleus of the hypothalamus following stimulation of the midbrain central gray revealed that estrogen decreased the antidromic activation threshold and shortened the absolute refractory period of the hypothalamic efferents along with the estrogen-induced behavioral activation in the experimental animals. In the control group, the estrogen-induced neuronal activation was lost altogether with the behavioral activation.

Relative contributions of the nervous system and hormones to CNS-mediated hyperglycemia.

We quantitatively determined the relative contributions of hormonal factors and the nervous system to the total glucose response after stimulation of the cholinergic neurons in the central nervous system of fed rats. Hepatic venous plasma glucose, glucagon, insulin, epinephrine, and norepinephrine were measured during 120 min after injection of neostigmine (5 X 10(-8) mol) into the third cerebral ventricle in rats subjected to bilateral adrenodemedullation (ADMX) to prevent epinephrine secretion (observed insulin secretion), with and without intravenous infusion of somatostatin to prevent glucagon and insulin secretion. Injection of neostigmine in intact rats resulted in increases in glucose, glucagon, epinephrine, and norepinephrine. Comparison of glucose areas suggests that 22% of the hyperglycemic response is due to the glucagon effect, that 29% is due to the epinephrine effect, and that an unknown factor other than epinephrine or glucagon, which may include activation through direct neural innervation of the liver via alpha-adrenergic receptor, contributes 49%. The suppressive effect of epinephrine on insulin secretion, which is potentially stimulated by direct neural activation of the pancreas, contributes 18% of the net hyperglycemia.

Influence of electrical stimulation of the limbic structure on ovarian steroidogenesis in hypophysectomized and adrenalectomized rats.

The effects of electrical stimulation of the medial amygdala (AMYG) and dorsal hippocampus (DHPC) on the rates of 14C transfer from 14C-1-acetate into ovarian steroids in hypophysectomized and adrenalectomized rats (H-A rats) were investigated. The 14C transfer rates into estrogen were increased by stimulation of AMYG and DHPC. The 14C transfer rates into progesterone and 20 alpha-hydroxy-pregn-4-en-3-one (20 alpha-OH-P) were increased by the AMYG stimulation but decreased by the DHPC stimulation. From these results, it might be suggested that these limbic structures were involved in the regulation of ovarian steroidogenesis without participation of pituitary and adrenal.

Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats.

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.