Probiotics promote rapid-turnover protein production by restoring gut flora in patients with alcoholic liver cirrhosis

Background and aims

Accumulating evidence suggests that deterioration of the gut flora contributes to the pathogenesis of alcoholic liver cirrhosis (ALC). However, the ALC flora profile and its response to probiotic treatment have not been fully examined. This double-blind placebo-controlled study aimed to evaluate whether the probiotic beverage Yakult 400 (Y400), which contains Lactobacillus casei strain Shirota, improves liver function in ALC patients, and to analyze the precise gut flora profile by real-time quantitative PCR (qPCR).

Methods

A total of 37 hospitalized ALC patients were randomly allocated to Y400 (n = 18) and placebo (n = 19) groups. Y400 or placebo was served twice a day during the first half of the four-week study. Serum concentrations of rapid-turnover proteins (i.e., transthyretin and transferrin), hypersensitive C-reactive protein, and interleukin-6 were measured weekly. qPCR analysis of fecal bacteria was performed biweekly; stocked fecal samples from 46 healthy subjects were used as references.

Results

Serum transthyretin levels significantly increased in the Y400 group in week 3; similar—although statistically insignificant—increases were seen for transferrin and albumin. Levels of hypersensitive C-reactive protein, but not interleukin-6, significantly decreased in week 4. Before treatment, populations of obligate anerobic bacteria were significantly smaller and those of Enterobacteriaceae were larger in patients than in healthy subjects examined in a previous study. Y400 corrected this imbalance.

Conclusions

This is the first report describing the unique gut flora of ALC patients. Y400 treatment normalized the gut flora and improved liver function. These promising findings warrant further investigation in larger, multicenter studies.     

Rational surgical operations for advanced cancers located in the middle of the stomach

Before 1982, total gastrectomy with pancreaticosplenectomy was performed for advanced gastric carcinoma which exposed to the serosa and was located in the middle of the stomach (M). The results of that surgical treatment were evaluated, and new surgical approaches were expected to provide a much better prognosis to patients. (1) A radical surgical operation, left upper abdominal evisceration + Appleby's method (LUAE + Apl), was tried for Borrmann type 4 gastric cancers from 1983. The 3-year survival after LUAE + Apl (77.9%) was better than that after total gastrectomy with pancreaticosplenectomy (35.0%) (p less than 0.05). In terms of the postoperative condition, no significant differences were observed between both operations. (2) As a conservative operation, total gastrectomy with resection of the spleen and splenic artery (Group A) was compared with total gastrectomy plus pancreaticosplenectomy (Group B) in patients with advanced gastric carcinoma other than Borrmann type 4. The 5-year survival was similar in both groups. The incidence of postoperative disorders was lower in Group A than in Group B (p less than 0.05). LUAE + Apl for Borrmann type 4 and total gastrectomy with resection of the spleen and splenic artery for the other advanced gastric cancers led to good results. These rational surgical operations will be necessary to achieve a good quality of life for the patients.     

Demonstration of polyclonal origin of giant fibroadenoma of the breast

We have shown that fibroadenoma of the breast is polyclonal and that phyllodes tumour is monoclonal in origin. It is not known whether a giant fibroadenoma which is histologically identical to the more usual type of fibroadenoma but grows to be a huge mass, like a phyllodes tumour, is polyclonal or monoclona. Clonal analysis was conducted on the DNA samples extracted from the paraffin sections of a giant fibroadenoma resected from a 21-year-old woman. The method used was based on trinucleotide repeat polymorphism of the X-chromosome-linked androgen receptor gene and on random inactivation of the gene by methylation. Clonal analysis showed that the giant fibroadenoma and the adjacent normal breast tissue are polyclonal in origin. Although the term giant fibroadenoma has often been used interchangeably with the term benign phyllodes tumour, because of their similarity in clinical appearance, our present results demonstrate that a giant fibroadenoma is a polyclonal fibroadenoma that has attained an immense size and is different from the monoclonal phyllodes tumour.     

Prognostic application of magnetic resonance imaging in patients with endometriomas treated with gonadotrophin-releasing hormone analogue

We evaluated the usefulness of magnetic resonance imaging (MRI)for assessing the response of patients with endometri-omas tomedical therapy. MRI was performed before and after treatmentin 20 consecutive patients with at least one endometrioma witha maximal diameter >10 mm diagnosed by laparoscopy who received900 µg of buserelin acetate daily for 6 months. Patientswere categorized as good responders (group I, n = 13) and poorresponders (group n, n = 7) depending on the results of a third-looklaparoscopy performed 6 months after treatment We determinedthe ratio of the signal intensity (SI) of the endometrioma tothe SI of the gluteus maximus muscle on T2-weighted images [T2SI/M(muscle) SI] and the volume of the endometrioma. The volumedecreased by >50% in 61.5% of the good-response group and57.1% of the poor-response group. There was no significant differencebetween the two groups. The T2SI/MSI decreased in 12 of 13 patientsin group I but in only one of seven patients in group II, asignificant difference (P < 0.05) between the two groups.In the good-response group, there was a positive linear correlationbetween the decrease in the volume of the endometrioma and thedecrease in the T2SI/MSI after treatment (r = 0.561, P <0.05). Therefore, the T2SI/MSI determined from MR images maybe useful in assessing the therapeutic response of patientswith endometriomas.     

Mediation of arachidonic acid metabolite(s) produced by endothelial cytochrome P-450 3A4 in monkey arterial relaxation.

We investigated mechanisms of endothelium-dependent relaxation by acetylcholine resistant to indomethacin and N(G)-nitro-L-arginine and sensitive to cytochrome P-450 (CYP) inhibitors or charybdotoxin + apamin in the monkey lingual artery. Treatment with quinacrine, an inhibitor of phospholipase A2, abolished the relaxation by acetylcholine. However, treatment with alpha-glycyrrhetinic acid, an inhibitor of gap junctions, or catalase, an enzyme which dismutates hydrogen peroxide to form water and oxygen, did not affect the relaxation by acetylcholine. Immunohistochemistry demonstrated the presence of CYP3A4 in endothelial cells of the artery. Anti-CYP3A4 antibody inhibited relaxations by products of arachidonic acid incubated with human liver microsomes rich in CYPs in the endothelium-denuded artery. Purified CYP3A4 produced epoxyeicosatrienoic acids (EETs) from arachidonic acid, and the production was abolished by a selective CYP3A inhibitor, ketoconazole. It may be concluded that endothelium-derived relaxing substance(s) other than nitric oxide and prostanoids in the monkey lingual artery opens charybdotoxin + apamin-sensitive K+ channels in smooth muscle cells, and arachidonic acid metabolite(s) produced by endothelial CYP3A4 is likely to be the major substance.     

Anticancer effect of UFT in intrahepatic recurrence with tumor embolus in the left portal vein after hepatectomy of hepatoma--a case report

A 65-year-old man was diagnosed as having hepatoma (HCC) in the area of S5 and S8. Anterior segmentectomy was performed on September, 1984. TAE (Sandwich therapy) via r. hepatic artery was performed for the intrahepatic recurrence one and half years after hepatectomy. However, the tumor embolus in the l. portal vein with intrahepatic recurrence occurred, and intraarterial infusion chemotherapy (IAC) using CDDP 150 mg was performed via proper hepatic artery. The decrement of AFP value was observed for a short time after IAC therapy. Therefore, UFT 300 mg daily, was administered. For two and half months after UFT administration, the elevation of AFP value continued from 665 ng/ml to 4150 ng/ml, and decreased rapidly below 20 ng/ml in the following 2 months. The tumor embolus in the l. portal vein was remarkably reduced on computed tomogram examination. This case suggests the usefulness of UFT for the intrahepatic recurrence with tumor embolus in the portal vein after hepatectomy for HCC.     

Effects of the plasma concentration of 5-fluorouracil and the duration of continuous venous infusion of 5-fluorouracil with an inhibitor of 5-fluorouracil degradation on Yoshida sarcomas in rats

The correlations of the 5-fluorouracil (5-FU) level in the plasma and the duration of continuous 5-FU infusion with the antitumor activity of 5-FU on Yoshida sarcomas in rats were examined. The circadian variation in the plasma level of 5-FU during continuous infusion was prevented by treatment with 3-cyano-2,6-dihydroxypyridine (CNDP), which strongly inhibits 5-FU degradation. On continuous venous infusion of 2 to 30 mg/kg of 5-FU over 24 h with CNDP at a molar ratio of 1:10 into normal rats, the 5-FU level in the blood was linearly proportional to the dose of 5-FU. The optimum schedule for antitumor activity on Yoshida sarcomas in rats was found to be infusion of 5-FU at 5 mg/kg over 24 h for 6 consecutive days, which gave a plasma 5-FU level of 176 ng/ml. Continuous infusion of 5-FU to give a plasma level of 300 ng/ml for 6 consecutive days from day 5 after implantation of tumor cells, when the tumors weighed about 1.0 g, resulted in complete regression of the tumors in all rats.