The Effect of Branched Chain Amino Acids-Enriched Nutritional Supplements on Activities of Daily Living and Muscle Mass in Inpatients with Gait Impairments: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of continuous intervention with branched chain amino acids-enriched nutritional supplements from the acute phase to convalescent rehabilitation wards in inpatients with gait impairments. DESIGN: Open-label, randomized, parallel-group comparison study (UMIN Clinical Trials Registry ID: UMIN000018640). SETTING: Acute care and convalescent rehabilitation wards. PARTICIPANTS: We studied 80 patients undergoing stand/gait training. INTERVENTIONS: Participants in the intervention group (RJ group) received nutritional supplements (jelly foods comprising 2500 mg BCAA and 20 IU vitamin D) twice a day until hospital discharge. MEASUREMENTS: The primary outcome was the motor components of the Functional Independence Measure (FIM-m), and the secondary outcome was skeletal muscle mass index. RESULTS: Analyses were conducted on 55 patients who were able to perform stand/gait training continuously from the acute until the recovery phases. FIM-m was significantly elevated in the RJ group and the control group , but no difference was noted between the two groups. Only the RJ group showed a significant increase in skeletal muscle mass index, and the amount of variation was significantly different between the two groups (the control group decreased an average of 2.2% and the RJ group increased an average of 4.3%; P = 0.014). A significant decrease in body weight was found only in the control group (P = 0.084). CONCLUSIONS: Nutritional interventions using branched chain amino acids (BCAA)-enriched nutritional supplements demonstrated no significant difference in activities of daily living; however, an increase in skeletal muscle mass was noted. Skeletal muscle mass and body weight differed significantly between the two groups, and BCAA-enriched nutritional supplements intake in acute and convalescent rehabilitation wards may be effective for the prevention of malnutrition and sarcopenia.

Effects of Nutrition Therapy in Older Stroke Patients Undergoing Rehabilitation: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review evidence on the effects of nutrition therapy in older stroke patients undergoing rehabilitation and identify its effectiveness using meta-analysis. METHODS: PubMed (MEDLINE), EMBASE (via Dialog), Cochrane Central Register of Controlled Trial, World Health Organization International Clinical Trials Registry Platform and Ichu-shi Web were searched for relevant articles. Randomized controlled trials investigating the effects of nutrition therapy compared to control interventions in older stroke patients undergoing rehabilitation were considered eligible. The primary outcome was activities of daily living (ADL), and secondary outcomes were all-cause mortality, infections, pneumonia incidence, disability level, walking ability, fall, stroke recurrence, and quality of life. The risk of bias of each trial was assessed using the Cochrane Collaboration Tool, and the quality of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Eight randomized controlled trials with a total of 5484 participants were included in the meta-analysis. The meta-analysis for ADL showed no significant effects (mean difference, 4.16; 95% confidence interval [CI], -0.88 to 9.20; I2=53%, low-quality evidence). The meta-analyses for secondary outcomes revealed a significant effect of reduced infections (risk ratio, 0.65; 95% CI, 0.51 to 0.84; I2=0%; low-quality evidence), with no significant effects on the other outcomes. CONCLUSION: Nutrition therapy had no statistically significant effect on ADL. However, it reduced the incidence of infections. More high-quality trials are warranted to clarify the effects of nutrition therapy in older stroke patients undergoing rehabilitation.

Oral administration of bovine lactoferrin attenuates ultraviolet B-induced skin photodamage in hairless mice.

Lactoferrin (LF) is recognized as a host defensive glycoprotein, especially for newborn infants. The aim of this study was to investigate whether orally administered LF had protective activity against UV-induced skin damage in hairless mice. Transepidermal water loss and skin hydration were evaluated in nonirradiated mice, UVB-irradiated mice, and UVB-irradiated and LF-administered mice. Supplementation with LF (1,600 mg/kg per day) effectively suppressed the increase in transepidermal water loss, reduction in skin hydration, aberrant epidermal hyperplasia, and cell apoptosis induced by UV irradiation. Although no significant changes in superoxide dismutase-like activity or malondialdehyde levels were observed in the skin with both UV irradiation and LF administration, UV-stimulated IL-1ß levels in the skin were significantly suppressed by the administration of LF. Oral supplementation with LF has the potential to reduce IL-1ß levels and prevent UV-induced skin damage. Further studies are needed to elucidate the relationships between the antiinflammatory effects and skin protective function of LF.

Do biologics-naïve patients with rheumatoid arthritis respond better to tocilizumab than patients for whom anti-TNF agents have failed? A retrospective study.

OBJECTIVES: To determine responses to tocilizumab between patients with rheumatoid arthritis (RA) who switched to anti-TNF agents and those who are biologics-naïve. METHODS: This retrospective study investigated 107 patients with RA who were treated with tocilizumab. At baseline, 61 of them had already been treated with anti-TNF agents (switched group; 46 for inefficacy and 15 for adverse events), and 46 were biologics-naïve (naïve group). Treatment responses to tocilizumab at week 12 and 24 were compared between the switched and naïve groups using the disease activity score 28 (DAS28). RESULTS: Forty-two (91.3%) and 50 (82.0%) patients in the naïve and switched groups, respectively, completed 24 weeks of tocilizumab treatment. The DAS28-ESR and DAS28-CRP values (means±SD) at weeks 12 and 24 compared to baseline decreased significantly for the naïve and switched groups. The DAS28-ESR and DAS28-CRP values at weeks 12 and 24 were significantly decreased in the naïve group, compared to the switched group. Disease activity was improved in the naïve patients compared to the switched patients. CONCLUSIONS: Tocilizumab was safe, tolerable, and clinically effective for patients with inadequate responses to anti-TNF therapy and for those who were biologics-naïve, and it was more effective among the latter.

Biological activity of a fruit vegetable, "Anastasia green", a species of sweet pepper.

Russian green sweet pepper (Anastasia Green) was successively extracted with hexane, acetone, methanol and 70% methanol and the extracts were further separated into a total of twenty fractions by silica gel or ODS column chromatographies. The biological activities of these extracts and fractions were compared. The extracts and fractions showed higher cytotoxic activity against two human oral tumor cell lines than against normal human gingival fibroblasts, suggesting their tumor-specific action. Several fractions [H3, H4, A4] reversed the multidrug resistant gene (MDR1) against L5178 mouse T-cell lymphoma more effectively than (+/-) verapamil (positive control). All extracts and fractions showed no anti-human immunodeficiency virus (HIV) nor anti-Helicobacter pylori activity. These data suggest the medicinal importance of an Anastasia Green extract.

Value of laparoscopic microwave coagulation therapy for hepatocellular carcinoma in relation to tumor size and location.

BACKGROUND AND STUDY AIMS: The indications for laparoscopic microwave coagulation therapy (LMCT) for hepatocellular carcinoma (HCC) have not yet been adequately evaluated. This study investigated the value of LMCT in the treatment of HCC. PATIENTS AND METHODS: Forty-three patients with liver cirrhosis (including five patients in Child Pugh grade C), with 56 HCC lesions, were enrolled in the study. When dynamic computed tomography (CT) showed a loss in HCC enhancement characteristics and a low concentration area after LMCT, a lesion was judged to have undergone complete necrosis. RESULTS: The rate of complete necrosis for lesions measuring 40 mm or less was significantly higher (P<0.01) than for those measuring 41 mm or more. The rate of complete necrosis for lesions located on the liver surface, excluding those located close to the gallbladder or in contact with the diaphragm, was also significantly higher (P<0.01) than for those situated deep within the liver. The outcome for lesions of 40 mm or less was favorable. Intra-abdominal hemorrhage occurred in two patients, pneumothorax in three, and hepatic infarction in one, all associated with LMCT. However, these patients did not suffer any sequelae of clinical significance. CONCLUSIONS: This study suggests that there is a strong indication for LMCT for HCCs measuring 40 mm or less in diameter and those located on the liver surface even if they are as large as 50 mm, but not for those located close to the gallbladder or in contact with the diaphragm. LMCT appears to be applicable in patients with impaired liver function.

Nutritional therapy of chronic hepatitis by whey protein (non-heated).

In an open study the clinical efficacy of milk serum (whey) protein (Immunocal; cysteine content: 7.6-fold higher than that of casein) isolated from fresh milk and purified without heating was evaluated in 25 patients with chronic hepatitis B or C. Immunocal (12 g as protein) food (mousse) was given twice a day, in the morning and evening, for 12 weeks (test period). Casein (12 g as protein) food (mousse) was similarly given for two weeks prior to the start of the supplement with Immunocal food (induction period) and for four weeks after the end of the supplement with Immunocal food (follow-up period). Serum alanine aminotransferase (ALT) activity was reduced, and plasma glutathione (GSH) levels increased in six and five of eight patients with chronic hepatitis B, respectively, 12 weeks after the start of the supplement with Immunocal food. Serum lipid peroxide levels significantly decreased, and interleukin (IL)-2 levels and natural killer (NK) activity significantly increased. However, there were no significant Immunocal-related changes in 17 patients with chronic hepatitis C. These findings suggest that the long-term supplement with Immunocal alone may be effective for improving liver dysfunctions in patients with chronic hepatitis B.

New ferromagnetic bone cement for local hyperthermia.

We have developed a ferromagnetic bone cement as a thermoseed to generate heat by hysteresis loss under an alternate magnetic field. This material resembles bioactive bone cement in composition, with a portion of the bioactive glass ceramic component replaced by magnetite (Fe3O4) powder. The temperature of this thermoseed rises in proportion to the weight ratio of magnetite powder, the volume of the thermoseed, and the intensity of the magnetic field. The heat-generating ability of this thermoseed implanted into rabbit and human cadaver tibiae was investigated by applying a magnetic field with a maximum of 300 Oe and 100 kHz. In this system, it is very easy to increase the temperature of the thermoseed in bone beyond 50 degrees C by adjusting the above-mentioned control factors. When the temperature of the thermoseed in rabbit tibiae was maintained at 50 to 60 degrees C, the temperature at the interface between the bone and muscle (cortical surface) surrounding the material rose to 43 to 45 degrees C; but at a 10-mm distance from the thermoseed in the medullary canal, the temperature did not exceed 40 degrees C. These results demonstrate that ferromagnetic bone cement may be applicable for the hyperthermic treatment of bone tumors.

Fatty acid composition and arachidonate metabolites in the livers of ethanol-treated rats fed an arachidonate-supplemented diet: effect of dietary fat.

The effects of 1% arachidonic acid ethyl ester (AA) administration on the liver prostanoid metabolites and on serum and liver lipids in 3 g/kg ethanol-administered rats fed 10% lard or corn oil were studied. The rats were divided into 6 groups: lard-sucrose (Lard-Suc); lard-ethanol without AA (Lard-Et); lard-ethanol with AA (Lard-EtAA); corn oil-sucrose (Corn-Suc); corn oil-ethanol without AA (Corn-Et); and corn oil-ethanol with AA (Corn-EtAA). Liver triglyceride increased in Corn-EtAA compared with Corn-Et. Arachidonic acid (20: 4n-6) levels in liver phospholipid were significantly decreased in Corn-Et, but elevated in Lard-Et. The levels of 20:4n-6 were significantly increased with AA administration in both ethanol groups. Liver 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in Corn-Suc (24.7 +/- 5.1 pg/mg protein) was markedly higher than in Lard-Suc (4.5 +/- 1.2 pg/mg protein), and the 6-keto-PGF1 alpha lowered significantly with the addition of ethanol (9.3 +/- 0.9 pg/mg protein), but it increased with AA administration (21.6 +/- 4.9 pg/mg protein). In Lard-EtAA, a significant increase in 6-keto-PGF1 alpha was observed compared with Lard-Suc. The liver leukotriene B4 (LTB4) level in Lard-Suc was significantly lower than that of Corn-Suc. In the corn oil group, ethanol feeding was associated with a significant increase in liver LTB4. AA administration to Corn-Et suppressed the elevated LTB4. Serum thiobarbituric acid-reactive substance (TBARS) concentrations in the corn oil group were higher than in the lard group, and these concentrations were not altered by AA administration. From these results, we concluded that the administration of AA in rats treated with ethanol increased 20:4n-6 in liver phospholipid and liver PGI2 levels, irrespective of dietary fat, and may protect against alcoholic liver injury. AA with a diet rich in linoleic acid (18:2n-6), however, may increase fat in the alcoholic liver.

Four new taxoids from Taxus cuspidata var. nana.

Four new taxoids ( 1- 4), showing cytotoxic activity, have been isolated from the stems of Taxus cuspidata Sieb. et. Zucc. var. nana Rehder. Their structures were elucidated by extensive 2D NMR methods including (1)H- (1)H COSY, TOCSY, HMBC, HMQC, and phase sensitive ROESY spectra.

Effect of arachidonate on lipid metabolism in ethanol-treated rats fed with lard.

Two groups of rats, ethanol-treated and sucrose-administered control rats, were fed diets with different AA content (0, 2 and 3% weight) for 14 days. Ethanol was administered by gavage at a single daily dose of 3 g/kg body weight. The ethanol-treated rats showed significantly higher levels (p < 0.01) of serum ALT activity. The dietary AA supplement lowered the serum ALT activity and liver triglyceride both in control and ethanol-treated rats. Significantly lower levels of 20:4n - 6 and 20:4n - 6/18:2n - 6 ratio and higher levels of 18:1n - 9 in both the serum and liver triglyceride were observed in the ethanol-treated rats. The AA-supplemented diet induced a marked increase of 20:4n - 6 and subsequent significant decrease of 18:2n - 6 both in the liver and serum phospholipid in control and ethanol-treated rats. 18:1n - 9 in the serum and liver triglyceride in both groups was also markedly decreased by AA supplement. No significant difference was observed in the liver 6-keto-PGF(1 alpha) level between the ethanol-treated and control rats. In the ethanol-treated rats, the level of 6-keto-PGF(1 alpha) was elevated in the rats fed the 3% AA-supplemented diet. Though the liver leukotriene B4 levels were increased by ethanol administration in all rats, these levels were not increased by dietary AA.

Protective effects of antithrombin III supplementation on warm ischemia and reperfusion injury in rat liver.

The effect of antithrombin III (AT III) supplementation on energy status, microcirculation, cytoprotection, and prostacyclin (PGI2) production during and after a period of warm ischemia of the rat liver was investigated. AT III supplementation (250 units/kg) stimulate prostaglandin I2 (PGI2) production from 1 hour after administration, with maximal production observed at 3 hours. Ischemia was induced by occluding the hepatoduodenal ligament for 30 minutes, and experiments were continued for 60 minutes after reperfusion. The rats received AT III (250 units/kg IC) 30 minutes before induction of liver ischemia (AT III group). In the AT III group, recovery of the beta-ATP/inorganic phosphate ratio measured by 31P nuclear magnetic resonance showed significant improvement (p < 0.01), and the recovery of tissue blood flow markedly improved (p < 0.01) compared to the saline-treated group (control group). Leakages of aspartame aminotransferase, alanine aminotransferase, and lactate dehydrogenase were mitigated in the AT III group (p < 0. 05). Ultrastructural alterations of sinusoidal endothelial cells were markedly reduced in the AT III group. The PGI2 level at the end of reperfusion was significantly elevated (p < 0.01) in the AT III group compared to the control group. The results of this study indicated that pretreatment with AT III significantly improved the energy status and microcirculation, as well as histologic damage, after liver ischemia and reperfusion. One of the fundamental effects of AT III might be mediated through the production of prostacyclin.

Nutrient-induced thermogenesis and protein-sparing effect by rapid infusion of a branched chain-enriched amino acid solution to cirrhotic patients.

An increase in the resting energy expenditure (REE) on indirect calorimetry was observed by rapid intravenous infusion of a branched chain-enriched amino acid solution into cirrhotic patients. The increases resulted in nutrient-induced thermogenesis (NIT). The percentage of energy expenditure (EE) derived from protein decreased significantly with the infusion of the amino acids. The present pilot study demonstrates that branched chain amino acids can be utilized as energy substrates and a protein-sparing effect occurs in patients with liver cirrhosis.

Evaluation of calcium hydroxide-containing root canal sealers with an improved rabbit ear chamber.

An improved rabbit ear chamber was used to evaluate calcium hydroxide-containing root canal sealers on their potential to induce dystrophic calcification in connective tissue. Four sealers and two control materials were introduced into the chambers and the effects of these materials on the living vascular tissue were observed continuously under a biomicroscope up to 9 weeks. Conventional histopathological investigation and examinations with a scanning electron microscope and an X-ray microanalyzer were done to supplement the results. Sealapex and Calvital (Ca(OH)2 + iodoform) revealed almost the same tissue reaction as calcium hydroxide-saline paste; they rapidly made a precipitate-barrier of calcium phosphate in the connective tissue, inducing calcification. However, Dentalis KEZ (ZnO-Ca(OH)2 + eugenol) caused mild disorders of microcirculation without calcification, as well as Canals (ZnO + eugenol). New A (Ca(OH)2 + fatty acid) had good compatibility with microvessels as well as New B (ZnO + fatty acid), however they induced no calcification and disintegrated rapidly in the tissue. These sealers were reclassified according to what they actually bring about in the tissue, not according to what they include.

[Warm ischemia and reperfusion injury in the regenerating rat liver].

The effect of warm ischemia and reperfusion injury in the regenerating rat liver after portal vein branch ligation (PBL) was examined by monitoring hepatic high energy phosphorous metabolism using in vivo Phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS). On 14 days after 70% occlusion of the portal vein, energy metabolism of non-occluded lobe of the liver was evaluated by measuring the ratio of beta-ATP to Pi obtained using 31P-MRS. During 30min-ischemia, beta-ATP/Pi dropped down similarly below the limit of observation in both of control and regenerating liver. However, after reperfusion, in the regenerating liver, the earlier and better recovery of beta-ATP/Pi was observed compared with the control. In the any examination of m-GOT, GPT, increase in enzyme level was apparently restrained in the PBL group. On the pathological examination, centrilobular necrosis and hepatocyte degeneration were remarkable in the normal liver, while in the regenerating liver, these changes were slight. In conclusion, these results suggest that reperfusion injury observed in the regenerating liver seems to be reduced compared with that in the normal liver. Functional and structural changes in the regenerating liver could be claimed as a course of this observation. However, to understand the mechanism, further study will be needed both in morphological and biochemical aspect.

[Clinical studies on the biliary excretion of mezlocillin, especially in cases with liver dysfunction].

To investigate efficacy of mezlocillin (MZPC) in the treatment of biliary tract infection, the time course concentrations of MZPC in the bile of patients with, in particular, liver dysfunction were measured. MZPC concentrations in the bile decreased with the increase in the severity of liver dysfunction. However, the bile concentration was maintained more than 50 micrograms/ml even in cases of severe cholangitis with obstructive jaundice. These results indicate that MZPC is an useful antibiotic for the treatment of biliary tract infection.