Ghrelin enhancer, rikkunshito, improves postprandial gastric motor dysfunction in an experimental stress model.

BACKGROUND: Functional dyspepsia (FD) is one of the most common disorders of gastrointestinal (GI) diseases. However, no curable treatment is available for FD because the detailed mechanism of GI dysfunction in stressed conditions remains unclear. We aimed to clarify the association between endogenous acylated ghrelin signaling and gastric motor dysfunction and explore the possibility of a drug with ghrelin signal-enhancing action for FD treatment. METHODS: Solid gastric emptying (GE) and plasma acylated ghrelin levels were evaluated in an urocortin1 (UCN1) -induced stress model. To clarify the role of acylated ghrelin on GI dysfunction in the model, exogenous acylated ghrelin, an endogenous ghrelin enhancer, rikkunshito, or an α2 -adrenergic receptor (AR) antagonist was administered. Postprandial motor function was investigated using a strain gauge force transducer in a free-moving condition. KEY RESULTS: Exogenous acylated ghrelin supplementation restored UCN1-induced delayed GE. Alpha2 -AR antagonist and rikkunshito inhibited the reduction in plasma acylated ghrelin and GE in the stress model. The action of rikkunshito on delayed GE was blocked by co-administration of the ghrelin receptor antagonist. UCN1 decreased the amplitude of contraction in the antrum while increasing it in the duodenum. The motility index of the antrum but not the duodenum was significantly reduced by UCN1 treatment, which was improved by acylated ghrelin or rikkunshito. CONCLUSIONS & INFERENCES: The UCN1-induced gastric motility dysfunction was mediated by abnormal acylated ghrelin dynamics. Supplementation of exogenous acylated ghrelin or enhancement of endogenous acylated ghrelin secretion by rikkunshito may be effective in treating functional GI disorders.

Variations in survival and perioperative complications between hospitals based on data from two phase III clinical trials for oesophageal cancer.

BACKGROUND: Variations in institutional practice may contribute to different outcomes of cancer treatment. The impact of interinstitutional heterogeneity on outcomes between hospitals after oesophagectomy has not been examined previously using data from surgical clinical trials. METHODS: The data from two phase III trials for oesophageal cancer were used. Japan Clinical Oncology Group (JCOG) 9204 involved oesophagectomy (92-OP) versus oesophagectomy plus postoperative chemotherapy (92-POST), with accrual from 1992 to 1997. JCOG9907 involved postoperative chemotherapy (99-POST) versus preoperative chemotherapy (99-PRE), with accrual from 2000 to 2006. Hospitals contributing fewer than three patients were excluded. The influence of time and preoperative chemotherapy on interinstitutional heterogeneity related to postoperative complications and 5-year overall survival were evaluated by comparisons within and between these trial groups. Heterogeneity was estimated by a mixed-effects model after adjusting for age, sex, performance status, location of the primary tumour and clinical stage. RESULTS: Twelve hospitals in 92-OP (114 patients), 13 in 92-POST (114), 19 in 99-POST (158) and 18 in 99-PRE (154) were eligible. There was considerable heterogeneity in predicted postoperative complications in both groups in JCOG9204 (median 31.3 (range 15.0-68.2) per cent), and in 99-PRE (35.2 (22.6-46.6) per cent) but not in 99-POST (27.7 (27.7-27.7) per cent) from JCOG9907. A similar pattern was seen for predicted overall survival (92-POST: 66.4 (range 64.1-68.9) per cent; 99-PRE: 55.9 (54.0-59.7) per cent; 99-POST: 44.4 (44.4-44.4) per cent). CONCLUSION: Interinstitutional heterogeneity regarding complications and survival after oesophagectomy is a problem that merits wider consideration.

Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium.

OBJECTIVE: Spinal cord tumours are highly malignant and often lead to paralysis and death due to their infiltrative nature, high recurrence rate and limited treatment options. In this study, we measured antitumour efficacy of the Salmonella typhimurium A1-R tumour-targeting bacterium strain, administered systemically or intrathecally, to spinal cord cancer in orthotopic mouse models. MATERIALS AND METHODS: Tumour fragments of U87-RFP were implanted by surgical orthotopic implantation into the dorsal site of the spinal cord. Five and 10 days after transplantation, eight mice in each group were treated with A1-R (2 x 10(7) CFU/200 microL i.v. injection or 2 x 10(6) CFU/10 microL intrathecal injection). RESULTS: Untreated mice showed progressive paralysis beginning at day 6 after tumour transplantation and developed complete paralysis between 18 and 25 days. Mice treated i.v. with A1-R had onset of paralysis at approximately 11 days and at 30 days; five mice developed complete paralysis, while the other three mice had partial paralysis. Mice treated by intrathecal injection of A1-R had onset of paralysis at approximately 18 days and one mouse was still not paralysed at day 30. Only one mouse developed complete paralysis at day 30 in this group. Intrathecally treated animals had a significantly better survival than the i.v. treated group as well as over the control group. CONCLUSIONS: These results suggest that S. typhimurium A1-R monotherapy can effectively treat spinal cord glioma.

O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) uptake in mouse thymoma cells, and its biodistribution in mice and human volunteers.

PURPOSE: To evaluate O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) uptake in mouse malignant thymoma (EL4), and its biodistribution in mice and humans. MATERIAL AND METHODS: First, 18F-FET uptake in EL4 cells was examined in an in vitro study. Second, the kinetics of 18F-FET uptake and its biodistribution were examined in mice after subcutaneous injection of EL4 cells and complete Freund's adjuvant. Finally, the kinetics of 18F-FET uptake and its biodistribution in healthy human volunteers were examined. RESULTS: In an in vitro study, 18F-FET was extensively incorporated in EL4 cells. In an animal study, 18F-FET accumulation in normal organs peaked within 30 min postinjection. The mean ratios of 18F-FET uptake in tumors and in inflammatory lesions to that in muscle tissue at 60 min postadministration were 2.18 (range 2.00-2.29) and 1.04 (range 0.95-1.14), respectively. In a human study, static images were taken 60 min after 18F-FET administration. Mean standardized uptake values (SUVs) of the liver (1.52, range 1.38-1.71) and kidneys (1.90, range 1.74-2.24) were nearly equal or slightly higher than that of muscle tissue (1.19, range 0.99-1.33). CONCLUSION: This study demonstrates that 18F-FET accumulation in thymoma is significantly higher than in normal organs. 18F-FET could be a useful tracer for tumor imaging.

A mixture of pure cellulase, hemicellulase and pectinase improves broiler performance.

1. The effects of a mixture of pure enzymes (cellulase, hemicellulase and pectinase) and a commercial enzyme, Energex, were examined on performance and metabolisabilities in broiler chicks given a maize-soybean meal diet. Composition of the mixed enzyme was similar to Energex except that protease was not present. 2. Chicks were divided into three groups: control, mixed enzyme and Energex with 7 replicates per group. Male broiler chicks were raised at 25 degrees C in wire-floored cages for 12 d from 15 d of age. Feed and water were offered ad libitum. 3. The Energex group gained significantly more weight and the mixed enzyme group tended to gain more than the control. Feed intakes were similar and thus the feed conversion ratio of Energex was significantly improved while it tended to be improved by the mixed enzyme. 4. The mixed enzyme group showed significant improvement in carcase and muscle weight when compared with the control group. The mixed enzyme group also showed significant improvement in organic matter and crude protein metabolisabilities. In the groups given enzyme, abdominal fat weight tended to decrease. 5. It is concluded that a combination of cellulase, hemicellulase and pectinase is effective in improving organic matter and crude protein metabolisabilities and carcase yield of broilers on a maize-soybean meal diet.

Tea polyphenols reduce glucocorticoid-induced growth inhibition and oxidative stress in broiler chickens.

1. The effects of dietary polyphenols (PP) on growth and oxidative stress in the corticosterone (CTC) treated broiler chickens model were studied. 2. Chicks (Cobb strain) were divided into 3 (CTC) x 3 (PP) blocks and given diets containing CTC at concentrations of 0, 10 and 20 mg/kg. 3. The body weight gain was lower when the birds were treated with CTC. However, the high dose of PP tended to reduce the effect of CTC. 4. The abdominal fat content, plasma triglyceride concentration and liver weight were increased by CTC and reduced by PP. 5. Muscle and liver thiobarbituric acid reactive substance (TBARS) were elevated by CTC and these effects were reduced by PP. Plasma CTC concentration was increased by dietary CTC treatment and decreased by PP. 6. In conclusion, our results indicate that PP can minimise growth inhibition, hyperlipidemia and oxidative stress induced by CTC treatment in broiler chickens.

Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407).

BACKGROUND: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted. METHODS: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible. RESULTS: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity. CONCLUSION: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.

A newly established strain of spontaneously hypertensive rat with a defect of ascorbic acid biosynthesis.

To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, we established a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis. The od gene (L-gulono-gamma-lactone oxidase gene) of the ODS (Osteogenic Disorder Shionogi) rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR), and a novel congenic strain, SHR-od, was established. SHR-od showed scurvy when fed an ascorbic acid-free diet. Systolic blood pressure of male SHR-od began to increase at 9 weeks of age and reached 190-200 mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed an ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure to lower than 110 mmHg. The wall to lumen ratio of the testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When rats were fed a diet supplemented with ascorbic acid (300 mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than that in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. We believe that SHR-od will be a useful model for experimental studies on hypertension and its complications, since all of them suffer from hypertension spontaneously and the level of ascorbic acid deficiency in these rats could be controlled at will both in concentration and duration.

Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray.

To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and systematically analyzed the expression pattern of the human NK/T cell line (NK-YS) genome by cDNA expression array and tissue microarray. We detected significant changes in the gene expression of NK-YS cell line: an increase in 18 and a decrease in 20 genes compared to normal NK cells or peripheral blood mononuclear cells. Among these genes, we found a strong decrease in hematopoietic cell specific protein-tyrosine-phosphatase SH-PTP1 (SHP1) mRNA by cDNA expression array and reverse transcriptase-polymerase chain reaction. Further analysis with standard immunohistochemistry and tissue microarray, which used 207 paraffin-embedded specimens of various kinds of malignant lymphomas, showed that 100% of NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma were negative for SHP1 protein expression. On the other hand, SHP1 protein was strongly expressed in the mantle zone and interfollicular zone lymphocytes in reactive lymphoid hyperplasia specimens. In addition, various kinds of hematopoietic cell lines, particularly the highly aggressive lymphoma/leukemia lines, lacked SHP1 expression in vitro, suggesting that loss of SHP1 expression may be related to not only malignant transformation, but also tumor cell aggressiveness. SHP1 expression could not be induced in either of two NK/T cell lines by phorbol ester, suggesting that genetic impairment or modification with methylation of SHP1 DNA could be one of the critical events in the pathogenesis of NK/T lymphoma. This evidence strongly suggests that loss of SHP1 gene expression plays an important role in multistep tumorigenesis, possibly as an anti-oncogene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.

Effects of baicalein isolated from Scutellaria baicalensis Radix on adhesion molecule expression induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells.

We examined the effects of various flavonoids isolated from the roots of Scutellaria baicalensis Georgi on adhesion molecule expression induced by thrombin and thrombin receptor agonist peptide (SFLLRNPNDKYEPF, TRAP) in cultured human umbilical vein endothelial cells. Thrombin and thrombin receptor agonist peptide induced endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Intercellular adhesion molecule-1 (ICAM-1) expression was also induced by thrombin, but not by TRAP. Baicalein isolated from Scutellariae Radix inhibited ELAM-1 expression induced by thrombin and thrombin receptor agonist peptide dose-dependently, with 50% inhibitory concentrations (IC50) of 5.53 +/- 1.68 microM and 2.44 +/- 1.08 microM, respectively. Furthermore, baicalein inhibited thrombin-induced ICAM-1 expression with an IC50 of 9.67 +/- 1.28 microM. In addition, baicalein inhibited the expressions of ELAM-1 and ICAM-1 stimulated by protein kinase C (PKC) activator phorbol myristate acetate (PMA).

A high dose of vitamin E inhibits adrenal corticosterone synthesis in chickens treated with ACTH.

The present experiment was conducted to study the effects of dietary vitamin E on plasma corticosterone (CTC) concentration and adrenal steroid syntheses in chickens treated with adrenocorticotropic hormone (ACTH). Chickens were divided into ACTH(-) and ACTH(+) groups, and each group was further divided into three subgroups administered with vitamin E (500 or 5,000 mg/kg diet) and without the vitamin. Vitamin E (DL-alpha-tocopheryl acetate) was mixed with the basal diet at levels of 500 and 5,000 mg/kg and fed for 6 d. ACTH (20 IU/kg body weight) was given daily by intraperitoneal injection for 5 d. alpha-Tocopherol levels in the plasma and adrenal gland were markedly elevated by vitamin E feeding, and the level of adrenal free cholesterol (CHOL), which is used for steroid synthesis, was significantly decreased by vitamin E feeding in a dose-dependent manner. However, the level of adrenal CHOL ester was unchanged by any treatment. The elevations of pregnenolone, progesterone and CTC levels in the adrenal gland of chickens with ACTH treatment were decreased by vitamin E administration. The elevation of plasma CTC concentration in the ACTH(+) group was dramatically decreased by vitamin E administration, while that concentration was not influenced by the vitamin administration in the ACTH(-) group. These findings indicate that vitamin E suppresses the elevation of the plasma CTC concentration due to ACTH in chickens, possibly by inhibiting the conversion of CHOL ester to free CHOL in the adrenal gland.

Activity of anthocyanins from fruit extract of Ribes nigrum L. against influenza A and B viruses.

Earlier, we have detected antiviral activity in an extract from Ribes nigrum L. fruits ("Kurokarin", name of the one species of black currant in Japanese) against influenza A and B viruses, and herpes simplex virus 1 (Knox et al., Food Processing 33, 21-23, 1998). In the present study, the antiviral activity of constituents of a Kurokarin extract and the mechanism of its antiviral action were examined. Kurokarin extracts were separated to fractions A to D by column chromatography. The major constituents of the fraction D were estimated as anthocyanins. The fraction D was further fractionated by thin-layer chromatography (TLC) to fractions A' to G'. The fraction E' consisted of 3-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranosyl-cyanidin and 3-O-beta-D-glucopyranosyl-cyanidin, and the fraction F' consisted of 3-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranosyl-delphinidin and 3-O-beta-D-glucopyranosyl-delphinidin, identified by high performance liquid chromatography (HPLC) with standards and by high resolution mass spectrometry. The fractions D' to G' showed potent antiviral activity against influenza viruses A and B. The additive antiviral effect of a combination of the fractions E' and F' was assessed. Anthocyanins in the fraction F' did not directly inactivate influenza viruses A and B, but they inhibited virus adsorption to cells and also virus release from infected cells.

Substrate specificity of beta-primeverosidase, a key enzyme in aroma formation during oolong tea and black tea manufacturing.

We synthesized nine kinds of diglycosides and a monoglycoside of 2-phenylethanol to investigate the substrate specificity of the purified beta-primeverosidase from fresh leaves of a tea cultivar (Camellia sinensis var. sinensis cv. Yabukita) in comparison with the apparent substrate specificity of the crude enzyme extract from tea leaves. The crude enzyme extract mainly showed beta-primeverosidase activity, although monoglycosidases activity was present to some extent. The purified beta-primeverosidase showed very narrow substrate specificity with respect to the glycon moiety, and especially prominent specificity for the beta-primeverosyl (6-O-beta-D-xylopyranosyl-beta-D-glucopyranosyl) moiety. The enzymes hydrolyzed naturally occurring diglycosides such as beta-primeveroside, beta-vicianoside, beta-acuminoside, beta-gentiobioside and 6-O-alpha-L-arabinofuranosyl-beta-D-glucopyranoside, but were unable to hydrolyze synthetic unnatural diglycosides. The purified enzyme was inactive toward 2-phenylethyl beta-D-glucopyranoside. The enzyme hydrolyzed each of the diglycosides into the corresponding disaccharide and 2-phenylethanol. These results indicate the beta-primeverosidase, a diglycosidase, to be a key enzyme involved in aroma formation during the tea manufacturing process.

Vatanidipine hydrochloride: a new long-lasting antihypertensive agent.

Vatanidipine is a novel dihydropyridine (DHP)-type calcium channel blocker with slow-onset pharmacological actions, which are probably due to both its slow uptake into vascular tissues and resistance in its approach to the calcium channel binding site. Vatanidipine once incorporated into vascular tissues is not easily released, even by repeated washing, thus resulting in a long-lasting action of the agent. A slow-onset and long-lasting hypotensive action was observed in various experimental hypertensive models. Clinical trials using human subjects with essential hypertension indicated that vatanidipine exerts an antihypertensive effect with a slow onset and long duration. In spite of its potent hypotensive effect, the incidence of adverse effects by vatanidipine administration has been reported to be lower than that in cases of nitrendipine. In addition to its vasodilatory effects, vatanidipine efficiently suppressed noradrenaline release from sympathetic nerve endings, thus suggesting this agent exhibits a beneficial effect in the treatment of hypertensive patients, in which the reflex activation of peripheral sympathetic nerves is unfavourable to antihypertensive therapy. In a double-blind study, vatanidipine did not show reflex tachycardia, despite producing a potent and long-lasting hypotensive effect, in contrast to the administration of nitrendipine. In an animal study, vatanidipine exhibited a protective effect against cerebrovascular lesions, through a mechanism independent of its hypotensive effect. In addition, a renoprotective effect was also observed in experimental hypertensive models. In cholesterol-fed rabbits, vatanidipine exerted an anti-atherosclerotic action, which is probably attributable to the inhibitory action of the agent on low-density lipoprotein oxidation. In essential hypertensive patients, the plasma levels of cholesterol and triglyceride decreased after vatanidipine treatment, thus suggesting that this agent may have a therapeutic potential in preventing such vascular diseases as atherosclerosis. Taken together, vatanidipine appears to be a novel and useful antihypertensive agent, which can both prevent target-organ damage and reduce cardiovascular morbidity and mortality.

The effect of monopolar radiofrequency treatment pattern on joint capsular healing. In vitro and in vivo studies using an ovine model.

The purpose of this study was to compare joint capsular healing after two delivery patterns of monopolar radiofrequency energy: 1) uniform treatment of the joint capsule (paintbrush pattern) and 2) multiple single linear passes (grid pattern). First, an in vitro study was performed to compare the percent shrinkage of these two treatment patterns using the femoropatellar joints (stifles) of six sheep. Monopolar radiofrequency energy (settings, 70 degrees C/15W) was applied to the lateral joint capsule; the treated area was approximately 10 x 10 mm. There was no significant difference in shrinkage between the grid (27% +/- 8.7%) and paintbrush (29% +/- 7.9%) patterns. In the in vivo study, stifles of 24 sheep were randomly assigned to the paintbrush or the grid pattern groups and treatment was performed arthroscopically. Sheep were sacrificed immediately after surgery, or at 2, 6, or 12 weeks after surgery. At 6 weeks after surgery, confocal microscopy demonstrated that treated areas had almost completely repaired in the grid group; some nonviable areas were still present in the paintbrush group. Mechanical testing at 6 weeks indicated that joint capsule in the grid group had better mechanical properties than capsule in the paintbrush group. This study revealed that radiofrequency treatment of joint capsule in a grid pattern allowed faster healing than tissue treated in a paintbrush pattern.

Midgut malrotation in adulthood.

A 29-year-old man was admitted to our hospital with a history of recurrent right upper quadrant abdominal pain and vomiting. These symptoms appeared intermittently for 7 years. Various examinations revealed a diagnosis of midgut malrotation. Laparotomy was performed and revealed reverse rotation of the duodenum with paraduodenal hernia and a normal rotating colon. This case suggests that recurrent abdominal complaints in an adult should arouse suspicion of midgut malrotation.

Inactivation of human type A and B influenza viruses by tea-seed saponins.

The effects of a mixture of tea-seed saponins obtained from the seeds of Camellia sinensis var. sinesis on human influenza viruses types A and B were investigated. At the concentrations of 60, 80, and 100 micrograms/ml, respectively, the mixture inactivated viruses A/Memphis/1/71 (H3N2), B/Lee/40, and A/PR/8/34 (H1N1) almost completely. The mixture also inactivated type A virus A/PR/8/34 after inoculation at concentrations of 1-30 micrograms/ml dose-dependently.

Selenium influences growth via thyroid hormone status in broiler chickens.

As there is a possibility that Se influences the growth of animals via thyroid hormone metabolism, the following three experiments were undertaken in order to determine the effects of dietary Se on growth, skeletal muscle protein turnover and thyroid hormone status in broiler chickens. Broiler chickens were raised on a Se-deficient diet until 12 d of age and then used for the experiments. In Experiment 1, twenty-eight birds were randomly assigned to four groups and fed purified diets with the following amounts of Se supplementation: 0.0, 0.1, 0.3 and 0.5 mg Se/kg diet. Dietary Se supplementation significantly increased plasma 3,5,3'-triiodothyronine (T3) concentration and improved growth, while plasma thyroxine (T4) concentration was decreased. In Experiment 2, twenty-eight birds were assigned to four groups and fed either a Se-deficient diet or a Se-supplemented diet (0.3 mg Se/kg diet) with or without the supplementation of iopanoic acid, a specific inhibitor of 5'-deiodinase (5 mg/kg diet). The growth was promoted and feed efficiency was improved by dietary Se supplementation as was also observed in Experiment 1. However, this effect of Se was halted by iopanoic acid supplementation. Hepatic 5'-deiodinase activity was elevated by Se and inhibited by iopanoic acid. In Experiment 3, birds were fed on the following diets to show that Se influences growth of birds via thyroid hormone metabolism: Se-deficient diet, Se-supplemented diets (0.1 and 0.3 mg/kg) and T3 supplemented diets (0.1 and 0.3 mg/kg diet). Lower dietary T3 supplementation (0.1 mg/kg diet) resulted in growth promotion similar to Se supplementation, while higher level of T3 caused growth depression. Furthermore, it was observed that the rate of skeletal muscle protein breakdown tended to be increased by Se similarly to the effect of T3. In conclusion, it was shown in the present study that Se deficiency depresses growth of broilers by inhibiting hepatic 5'-deiodinase activity which causes lower plasma T3 concentration.