Does the control of alanine aminotransferase levels lead to a regression of liver fibrosis in chronic hepatitis C patients?

The aim of this study was to investigate the effect of various medications other than interferon (IFN) on liver fibrosis in chronic hepatitis C (CH-C) patients, and the results were compared with those obtained in CH-C patients without therapy. Fifty CH-C patients (32 men and 18 women; mean age 58.5 years) without previous IFN therapy, who randomly received medicines other than IFN such as Stronger Neo-Minophagen C, Ursodeoxycholic acid and a herbal medicine, Sho-saiko-to (TJ-9) (Group I), and as a control group, 45 CH-C patients (27 men and 18 women; mean age 56.6 years) without therapy (Group II) were examined. All patients had persistent alanine aminotransferase (ALT) elevation more than 6 months before this study and were also subdivided into three subgroups according to different pattern of ALT during the observation period, i.e. (a): persistently ALT<60 IU/l (below about twice the upper limit of normal range); (b): persistently ALT>/=60 IU/l; and (c) other than (a) and (b). All patients were biopsied twice before starting this study and during observation period and the liver fibrosis was compared between them by staging in each case. When the fibrosis stage was the same between two specimens, we determined whether the degree of fibrosis had improved or worsened by computed image analysis. Blood tests for fibrosis marker, serum aminoterminal peptide of type III procollagen (P III P) and liver enzyme such as albumin (Alb) and zinc turbidity test (ZTT) levels, and platelet (Plt) counts were also examined on the two times of liver biopsy. As a result, there were no significant differences in fibrotic improvement rate when assessed by both staging only and staging together with fibrotic ratio, determined by computed image analysis and also in yearly change of P III P (P/Y) and fibrosis (F/Y), the changed rate of Alb, ZTT levels and Plt counts between Group I and Group II, except for P/Y in subgroup (a) which was rather higher in Group I than in Group II. There were also no significant relationship between the changes of histological activity and fibrosis staging in both groups. In conclusion, other medications than IFN could not significantly improve both liver fibrosis and its associated laboratory data irrespective of ALT levels in CH-C patients as compared to the control group during average 3 years' follow-up period.

Changes of liver fibrosis in chronic hepatitis C patients with no response to interferon-alpha therapy: including quantitative assessment by a morphometric method.

The aim of this study was to evaluate the antifibrotic effect of interferon (IFN)-alpha in chronic hepatitis C (CH-C) patients with no response to IFN-alpha therapy. We studied 76 patients (46 men, 30 women; mean age, 55.6 years) who received IFN-alpha intramuscularly, at a total close of 480 to 880MU for 6 months (group A). As a control group, we studied 50 patients (32 men and 18 women; mean age, 58.5 years) with CH-C who received medication other than IFN (ie, Strong-Neo-Minophagen C, ursodeoxycholic acid, and a herbal medicine, Sho-saiko-to [TJ-9]) and who had persistent alanine aminotransferase (ALT) elevation (group B). All patients were subdivided into three subgroups according to different patterns of ALT changes during the observation period, ie, (a) persistent ALT level < 60IU/ 1 (below about twice the upper limit of the normal range), (b) persistent ALT level > or = 60IU/1, (c) ALT levels other than (a) and (b). Liver biopsy was performed within 6 months prior to IFN therapy and more than 6 months after IFN therapy, while two liver biopsies were performed during therapy in group B. Liver fibrosis was compared between two specimens by staging. When the fibrosis stage was the same in the two specimens, we determined whether the fibrosis had improved or worsened by comparing the fibrotic ratio, ie, the ratio of the area of fibrosis to the area of the entire liver tissue specimen, calculated using computed graphic software. Serum aminoterminal peptide of type III procollagen (PIIIP) levels were measured on the day of the liver biopsy and their mean yearly changes were compared between the two groups. Improvement of liver fibrosis was found in 12% to 30% of patients in each ALT subgroup and in 24% of all patients in group A and there were no significant differences in liver fibrosis in comparison with findings in of group B when assessed by staging alone. However, these percentages rose to 59% to 75% and 66%, respectively, when liver fibrosis was assessed by the fibrotic ratio together with staging, resulting in a significant difference in fibrosis between groups A and B in total (P < 0.01). The mean yearly changes in serum PIIIP levels in each subgroup and in all patients in group A were below zero, indicating a tendency to improvement of fibrosis after IFN therapy, while these changes in group B were all above zero, except for subgroup (c). Improvement of fibrosis after IFN therapy was found in 15 of 24 patients (64%) whose ALT changes had the same pattern before and after IFN therapy, although no significant difference was noted between improved and worsened patients. These results suggest that IFN-alpha may have an antifibrotic effect even in CH-C patients with no overt response to IFN-alpha therapy, compared with the effect of medications other than IFN.

The inhibitory effect of funoran and eucalyptus extract-containing chewing gum on plaque formation.

The purpose of this study was to evaluate the inhibitory effect of funoran containing chewing gum (FG) and eucalyptus extract- containing chewing gum (EG) on plaque formation. Fifteen dentists or dental students were assigned a random order of use of either FG, EG or a control gum. All subjects received professional tooth cleanings before the experiment. During the four-day test periods, no oral hygiene measures were allowed other than chewing three pieces of gum for approximately 10 min daily. Chewing gum was used following each morning, noon and evening meal. Plaque formation was evaluated by the Quigley and Hein index. The FG (1.83 +/- 1.1) and EG (1.97 +/- 1.1) significantly reduced plaque compared to the control gum (2.57 +/- 1.2). Our results suggest that FG and EG may be useful in inhibiting dental plaque formation.

Effects of single and repeated administrations of Toki-shakuyaku-san on the concentrations of brain neurotransmitters in mice.

The amounts of monoamine-related substances (NE, MHPG, DA, DOPAC, HVA, 5-HT, and 5-HIAA and acetylcholine (ACh) in the cerebral cortex, corpus striatum and hippocampus of mice treated orally with a powdered extract of Toki-shakuyaku-san (TSS) were measured using the HPLC-ECD method. Single administration of TSS at 50 mg/kg decreased the content of NE in the hippocampus, but increased the contents of DA, DOPAC and HVA. Single administration of TSS at 50 mg/kg increased the contents of DA and HVA in the cerebral cortex and those of DA, DOPAC and HVA in the hippocampus, but decreased the content of NE. Repeated administration (twice a day, for 14 days) of TSS at 50 mg/kg increased the contents of DA, DOPAC and 5-HIAA in the cerebral cortex, while 500 mg/kg increased the contents of NE, MHPG, DOPAC, 5-HT and 5-HIAA in the cerebral cortex, and the NE and DA in the corpus striatum. With regard to ACh content, single and repeated administrations of TSS at 50 and 500 mg/kg had no influence in the three regions of mouse brain. These results suggest that single administration of TSS stimulates the function of the dopaminergic nervous system in the hippocampus in mice and inhabits the function of the adrenergic nervous system, and that repeated administration of TSS stimulates the function of the adrenergic, dopaminergic and serotonergic nervous systems in the cerebral cortex. TSS, however, did not show any influence on the brain ACh content in mice.

Inhibitory effects of acid water prepared by an electrolysis apparatus on early plaque formation on specimens of dentine.

The aim of this study was to compare the effects of acid water prepared by an electrolysis apparatus with placebo treatment on the ultrastructure of early plaque formed on dentine specimens attached to retainers in the oral cavity. Dentine specimens were taken from 12 healthy extracted human 3rd molars. 4 dentine specimens were placed in the both the right and left buccal flanges of retainers fabricated from self-setting acrylic resin. The retainers were placed on both maxillary buccal sites in 6 subjects. The test solution was acid water (AW) prepared by an electrolysis apparatus with a pH of 2.7 and an oxidation-reduction potential of more than 1100 mV. As a positive control, 0.2% chlorhexidine digluconate (CHX) solution was used and normal saline solution as a negative control. 4 specimens placed in the right and left retainers were randomly allocated to 4 treatments as follows: treatment A, washing with AW; treatment B, washing with CHX solution; treatment C, washing with normal saline; treatment D, no washing. Washing was carried out in a plastic beaker containing 30 ml of each solution for 30s 2X daily over a 7-day period. The specimens were then carefully removed from the retainers, the morphology and thickness of the plaque formed examined by SEM, and the developmental condition of the plaque analyzed statistically. The plaque on the specimens in treatments A and B consisted mainly of coccoid forms. Mature plaque formation with complex flora was seen on the specimens in treatments C and D. The mean thickness of the plaque deposits on the dentin specimens as measured on SEM photographs magnified 2000 times was 8.80 mm for treatment. A, while in treatment B it was 3.90 mm. Plaque thickness for treatment C was 24.97 mm, and for treatment D 25.67 mm. The thickness of plaque formed on the sectioned specimens was significantly less for treatments A and B than for treatments C and D. However, there was no statistically significant difference between treatments A and B, and between treatments C and D (p < 0.0001). The results of this short-term study indicate that AW washing has almost the same potential for inhibition of plaque formation as CHX washing, and is more effective for inhibiting plaque formation than washing with sterile saline. It is therefore concluded that AW may be useful as an anti-plaque agent.

Regulatory effect of danggui-shaoyao-san on central cholinergic nervous system dysfunction in mice.

Since administration of a powdered extract (TSS) of Danggui-Shaoyao-San (Toki-shakuyaku-san in Japanese) alone to naive mice had no influence on ACh levels in the brain, the present study examined the effect of TSS on the central cholinergic nervous system using mice treated with scopolamine (0.5 mg/kg) or mecamylamine (0.05 mg/kg), which affects the cholinergic nervous system. TSS was suspended in a 5% carboxymethylcellulose solution and mice were orally given single or repeated (twice a day, for 14 days) administration of TSS at 50 or 500 mg/kg. Results on spontaneous locomotor activity showed that (1) single administration of TSS at 50 or 500 mg/kg to naive mice significantly inhibited vertical and horizontal locomotor activities, while repeated administration of TSS at 50 mg/kg significantly stimulated both activities; (2) in mice treated with scopolamine, repeated administration of TSS at 500 mg/kg significantly inhibited the scopolamine-induced increase in locomotor activities, whereas in mice treated with mecamylamine, single or repeated administration of TSS at 50 and 500 mg/kg did not show any influence on the mecamylamine-induced decrease in locomotor activities. Regarding the step-down passive avoidance responses; single administration, but not repeated administration, of TSS at 50 and 500 mg/kg significantly inhibited scopolamine-induced shortening of step-down latency. In mice treated with mecamylamine, TSS did not exert any influence on the step-down latency. As for ACh contents, single or repeated administration of TSS at 50 or 500 mg/kg to naive mice had no influence on the levels of ACh in the cerebral cortex, corpus striatum or hippocampus. However, the levels of brain ACh in mice treated with scopolamine showed a decrease and a single administration of TSS at 500 mg/kg significantly inhibited this scopolamine-induced decrease in ACh levels. These results indicate that TSS ameliorates dysfunction of the central cholinergic nervous system and scopolamine-induced decrease in ACh levels in mouse brain, but has no influence on ACh levels in naive mice. Thus, it suggests that TSS may be a useful therapeutic agent in Alzheimer's disease and senile dementia.

Effects of chaihu-guizhi-ganjiang-tang on the levels of monoamines and their related substances, and acetylcholine in discrete brain regions of mice.

The effects of the extract powder (CggT) from Chaihu-Guizhi-Ganjiang-Tang (Saiko-keishi-kankyo-to, in Japanese) on the monoamines and their related substances and the acetylcholine in mouse brain were examined. 1) A single administration of CggT significantly increased the levels of HVA and 5-HIAA in the cerebral cortex, hypothalamus, corpus striatum and hippocampus at 75 mg/kg, and those in the hypothalamus, corpus striatum and hippocampus at 750 mg/kg. 2) The repeated administration of CggT significantly increased the level of 5-HT in the hippocampus at 75 mg/kg, and the levels of 5-HT in the corpus striatum and of NE and 5-HT in the hippocampus at 750 mg/kg. 3) The level of ACh was significantly increased in the hypothalamus alone after single administration of CggT. These findings suggest that CggT stimulates function of the dopaminergic and serotonergic nervous systems in mice, but not most of the NEnergic and cholinergic nervous systems.

Rapid HPLC assay with coulometric detection for norepinephrine and 3-methoxy-4-hydroxyphenylglycol in the mouse brain.

For the rapid assay of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) in the mouse brain, we developed a simple method using isocratic HPLC with coulometric detection. This method permits NE and MHPG assay within 5 min in one chromatographic run. Within-run coefficients of variation for NE and MHPG in the working standard solution were 0.8% and 0.6% (n = 50), respectively. The detector responses were linear from 0.025 to 100 pmol for NE and from 0.05 to 100 pmol for MHPG in the working standard solution. Using this method, the NE and MHPG concentrations were measured in discrete brain areas of the mouse prior treatment with or without alpha-methyl-p-tyrosine or N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4).

Effects of Panax ginseng root on the vertical and horizontal motor activities and on brain monoamine-related substances in mice.

Effects of the Panax ginseng root (PGR) on spontaneous motor activity (vertical and horizontal motor activities), and on monoamine-related substances (tyrosine, DA, DOPAC, 3-MT, HVA, NE, MHPG, tryptophan, 5-HT, and 5-HIAA) in discrete brain areas (cerebral cortex, hippocampus, hypothalamus, corpus striatum, limbic lobe, midbrain, cerebellum, and medulla oblongata) of ddY male mice (weighing 18-22 g) were examined using an infrared photo-cell counter and HPLC with electrochemical detection. PGR (100 mg/kg) was orally administered, twice a day, for 2 successive weeks (2W-group) or 7 successive weeks (7W-group). Vertical and horizontal motor activities increased significantly in the 7W-group but not in the 2W-group when compared to those of the control group. As to brain monoamine-related substances, the metabolism of DA and NE in the cerebral cortex and of 5-HT in the corpus striatum and cerebellum in the 2W-group were facilitated, while metabolism of DA in the corpus striatum and of 5-HT in the hypothalamus and midbrain were inhibited. In the 7W-group, except for a facilitated metabolism of 5-HT in the cerebellum, metabolism of DA, NE and 5-HT in all discrete brain areas were inhibited. These results show that PGR exerts an influence on the CNS.

[Clinical effects of chewing gum containing egg-white lysozyme and mace extract].

The purpose of this study was to evaluate the clinical effect of mace extract and egg-white lysozyme in two brands of chewing gum on gingival condition. Ever since mace extract containing dihydroguaiaretic acid was reported to inhibit the growth of Streptococcus mutans, plans were devised to include it in commercially available chewing gum. Before starting this study, two different types of experimental chewing gum containing mace extract or egg-white lysozyme were made up. A control was also prepared containing neither agent. The periodontal condition of 68 patients with gingivitis was determined based on PMA index (PMA), gingival index (GI), gingival bleeding index (GBI) and plaque scoring system (PSS) and randomly classified into three groups. Each group was instructed to use one or the other of the above type chewing gums after every meal. The results were as follows: 1. No clinical changes were observed in the control group during this study. 2. Gingival inflammation (PMA, GI, GBI) significantly improved as a result of using the experimental gums. 3. Plaque reduction was found only in the mece-extract gum group. 4. No clinical side effects were detected during this study.

Rapid determination of norepinephrine, dopamine, serotonin, their precursor amino acids, and related metabolites in discrete brain areas of mice within ten minutes by HPLC with electrochemical detection.

A rapid and simple chromatographic procedure using HPLC with electrochemical detection is described for simultaneous determination of the substrates from precursor amino acids to metabolites related to synthesis and metabolism of three monoamine neurotransmitters--norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin)--in discrete brain areas of the mouse. Under the present instrumental and mobile phase conditions, the procedure permits simultaneous determination of three monoamines (NE, DA, and 5-HT), two precursor amino acids (tyrosine and tryptophan), and four respective metabolites (3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid) within 10 min in one chromatographic run. By varying column temperature, this procedure also permits simultaneous determination of 10-14 monoamine-related substrates including the nine substrates described above within 15-21 min. The validity of the present procedure is demonstrated by analyzing the effect of an alpha 2-adrenergic agonist (clonidine) and an alpha 2-antagonist (yohimbine) in mouse hypothalamus.