Effects of perioperative exercise therapy combined with nutritional supplementation on functional recovery after fast-track total hip arthroplasty.

BACKGROUND: The combination of exercise therapy combined with nutritional supplementation (Nutr) is widely used for frail or sarcopenic older persons. However, the effects of Nutr in elderly patients after fast-track total hip arthroplasty (THA) are unknown. This study examined the effects of perioperative Nutr on muscle strength, functional performance, and quality of life (QOL) in frail elderly women after fast-track THA. METHODS: A total of 58 frail elderly women aged 65-80 years scheduled for unilateral primary THA were randomly allocated to two groups: the physical exercise (Ex) combined with Nutr (Ex + Nutr; n = 29) group, and the Ex alone (Ex; n = 29) group. Protein and vitamin D supplements were provided daily from 4 weeks preoperatively to 8 weeks postoperatively (12 weeks) to the patients in the Ex + Nutr group, whereas the Ex group did not receive any supplements. Surgery and postoperative rehabilitation programmes during intervention were identical in both groups. Hip abductor and knee extensor muscle strength, functional performance (Timed Up & Go test, Harris Hip Score), and QOL (Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire) were assessed at baseline and at 12 weeks (8 weeks postoperatively). RESULTS: After the intervention, hip abductor muscle strength on the contralateral leg and knee extensor muscle strength on both sides significantly improved in the Ex + Nutr group compared to the Ex group (p = 0.03, 0.01, and 0.01, respectively). However, hip abductor muscle strength on the operated side did not differ significantly between the groups (p = 0.23). There were no significant differences in functional performance and QOL. CONCLUSION: Ex + Nutr does not have an additional effect on the improvement of hip abductor strength, functional performance, and QOL compared to Ex alone after fast-track THA. However, significant improvements were observed in the strength of some muscles after fast-track THA. TRIAL REGISTRATION: UMIN 000042964. THE IRB APPROVAL: This study was approved by the Mirai Iryo Reesearch Center (approval number TGE1602-115).

Relationship between distal radius fracture severity and 25-hydroxyvitamin-D level among perimenopausal and postmenopausal women.

AIMS: Low-energy distal radius fractures (DRFs) are the most common upper arm fractures correlated with bone fragility. Vitamin D deficiency is an important risk factor associated with DRFs. However, the relationship between DRF severity and vitamin D deficiency is not elucidated. Therefore, this study aimed to identify the correlation between DRF severity and serum 25-hydroxyvitamin-D level, which is an indicator of vitamin D deficiency. METHODS: This multicentre retrospective observational study enrolled 122 female patients aged over 45 years with DRFs with extension deformity. DRF severity was assessed by three independent examiners using 3D CT. Moreover, it was categorized based on the AO classification, and the degree of articular and volar cortex comminution was evaluated. Articular comminution was defined as an articular fragment involving three or more fragments, and volar cortex comminution as a fracture in the volar cortex of the distal fragment. Serum 25-hydroxyvitamin-D level, bone metabolic markers, and bone mineral density (BMD) at the lumbar spine, hip, and wrist were evaluated six months after injury. According to DRF severity, serum 25-hydroxyvitamin-D level, parameters correlated with bone metabolism, and BMD was compared. RESULTS: The articular comminuted group (n = 28) had a significantly lower median serum 25-hydroxyvitamin-D level than the non-comminuted group (n = 94; 13.4 ng/ml (interquartile range (IQR) 9.8 to 17.3) vs 16.2 ng/ml (IQR 12.5 to 20.4); p = 0.005). The AO classification and volar cortex comminution were not correlated with the serum 25-hydroxyvitamin-D level. Bone metabolic markers and BMD did not significantly differ in terms of DRF severities. CONCLUSION: Articular comminuted DRF, referred to as AO C3 fracture, is significantly associated with low serum 25-hydroxyvitamin-D levels. Therefore, vitamin D3 supplementation for vitamin D deficiency might prevent articular comminuted DRFs. Nevertheless, further studies must be conducted to validate the results of the current study. Cite this article: Bone Jt Open 2022;3(3):261-267.

Identification of Acrylamide Adducts Generated during Storage of Canned Milk Coffee.

Since coffee is a significant contributor to the consumption of acrylamide, its reduction is required. Acrylamide is produced during the roasting of coffee beans, but the roasting process is an essential step in determining the taste of coffee. Acrylamide content in coffee has been suggested to decrease by reacting with proteins and/or other substances during storage, but details are unknown. Investigation of acrylamide adducts may contribute to a strategy for acrylamide reduction in coffee. In this study, a stable isotope labeling technique, combined with high-resolution mass spectrometry, allows the identification of acrylamide adducts (3-hydroxypyridine-acrylamide and pyridine-acrylamide) in canned milk coffee. Other acrylamide adducts derived from milk coffee proteins, Lys-acrylic acid and CysSO2-acrylic acid, were identified. During a 4-month storage period, the formation of these four adducts was found to reduce the total content of acrylamide by 75.3% in canned milk coffee. Therefore, endogenous proteins can be used in acrylamide reduction.

A highly sensitive determination method for acrylamide in beverages, grains, and confectioneries by supercritical fluid chromatography tandem mass spectrometry.

Acrylamide (AA) analysis is an important topic in food safety. However, it is difficult to rapidly and accurately analyze low concentrations of AA with currently available methods. In the present study, we introduce a highly sensitive method that enables the determination of AA in beverages, grains, and confectioneries by supercritical fluid chromatography tandem mass spectrometry (SFC/MS/MS). The sensitivity of the SFC/MS/MS technique is 11-times higher than that obtained by ultra-high performance liquid chromatography tandem mass spectrometry. We demonstrated that the highly sensitive SFC/MS/MS method was able to quantify low concentrations of AA in beverages (i.e., roasted barley tea and coffee) extracts at less than 10 µg kg-1 level without solid-phase purification. Furthermore, the simplification of the sample preparation procedure provided an improvement in data acquisition time (60 samples per 12 h). In conclusion, the developed analytical system is a potentially useful tool for practical AA determination.

Rhamnan sulfate extracted from Monostroma nitidum attenuates blood coagulation and inflammation of vascular endothelial cells.

Rhamnan sulfate (RS) is a polysaccharide with a rhamnose backbone isolated from Monostroma nitidum. Like heparin, it exerts anticoagulant activity in the presence of antithrombin. Endothelial cells facilitate the crosstalk between blood coagulation and vascular inflammation. In this study, we compared the effect of RS with that of heparin on blood coagulation and vascular endothelial cells in the presence or absence of inflammatory factors, using human umbilical vein endothelial cells. We found that RS significantly enhances inhibition of thrombin and factor Xa in the presence of antithrombin as well as heparin, and that RS inhibits tissue factor expression and von Willebrand factor release from the endothelial cells treated with or without lipopolysaccharide, tumor necrosis factor-α, or thrombin. Heparin did not show any effects on endothelial cell inflammation. Our findings suggest that RS, like heparin, is an antithrombin-dependent anticoagulant and, unlike heparin, is a potent anti-inflammatory agent acting on vascular endothelial cells.

p53 and ki67 as biomarkers in determining response to chemoprevention for oral leukoplakia.

BACKGROUND: We performed a randomized controlled chemoprevention trial of oral leukoplakia by administrating a low dose of beta-carotene and vitamin C supplements. 17% of subjects in the experimental arm (4/23) demonstrated clinical remission (complete or partial response) at completion of the trial. The objective of this study was to determine whether baseline expression of p53 and ki67 demonstrated any differences between those responding or not responding to our intervention. A secondary objective was to elucidate any relationship between dietary factors and clinical responses. METHODS: For this biomarker study, we included all subjects in the experimental group (n = 23) who were non-smokers. Among 16 who completed the trial for 1 year of supplementation, there were four responders and 12 non-responders at 1-year follow-up. Following immuno-staining for p53 and ki67, the percentage of positive cell nuclei were analyzed as labeling index (LI). RESULTS: Expression of p53 was greater in basal layers than in para-basal layers. Mean para-basal LI of p53 was higher in non-responding (26.0) than in responding subjects (11.2) (P = 0.028). ki67 LIs were not significantly different in the two groups. CONCLUSIONS: Expression of p53 was inversely related to clinical response to the supplements. Other biomarkers that may recognize subject's responsiveness to chemoprevention require further study.

Treatment of oral leukoplakia with a low-dose of beta-carotene and vitamin C supplements: a randomized controlled trial.

Management of oral leukoplakia-a potentially malignant disorder-is currently not evidence-based. Of the few randomized trials that have been reported, most have negative data. Therefore, a multi-centre, randomized, double-blind controlled trial (RCT) was undertaken to evaluate the use of low-dose beta-carotene combined with vitamin C supplements for the treatment and to prevent malignant transformation of oral leukoplakia. 46 Japanese participants with oral leukoplakia were allocated randomly either to an experimental arm (10 mg day(-1) of beta-carotene and 500 mg day(-1) of vitamin C) or placebo arm (50 mg day(-1) of vitamin C). Current or ex-smokers within 3 months of cessation were excluded. The supplements were continued over a period of 1 year. The primary endpoint was clinical remission at 1-year and the likelihood of malignant transformation during a 5-year follow-up period as a secondary endpoint. The overall clinical response rate in the experimental arm was 17.4% (4/23) and 4.3% (1/23) in the placebo arm (p = 0.346). During the median 60-month follow-up period, two subjects in the experimental arm and three in the control arm developed oral cancer. Under the intention-to-treat principle, relative risk by supplementing with beta-carotene and vitamin C was 0.77 (95%CI: 0.28-1.89) (p = 0.580) by the Cox proportional hazards model. No unfavorable side-effects were noted. Beta-carotene (10 mg day(-1) ) and vitamin C were neither effective for clinical remission, nor for protection against the development of cancer. Data from this RCT does not support the hypothesis that chemoprevention with this treatment is effective for oral leukoplakia.

Coffee consumption and risk of colorectal cancer: the Japan Collaborative Cohort Study.

BACKGROUND: Epidemiologic studies have reported coffee consumption to be associated with various health conditions. The purpose of this study was to examine the relationship of coffee consumption with colorectal cancer incidence in a large-scale prospective cohort study in Japan. METHODS: We used data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). Here, we analyzed a total of 58 221 persons (23 607 men, 34 614 women) followed from 1988 to the end of 2009. During 738 669 person-years of follow-up for the analysis of colorectal cancer risk with coffee consumption at baseline, we identified 687 cases of colon cancer (355 males and 332 females) and 314 cases of rectal cancer (202 males and 112 females). We used the Cox proportional-hazard regression model to estimate hazard ratio (HR). RESULTS: Compared to those who consumed less than 1 cup of coffee per day, men who consumed 2-3 cups of coffee per day had an HR of 1.26 (95% confidence interval [CI] 0.93-1.70), and men who consumed more than 4 cups of coffee per day had an HR of 1.79 (95% CI 1.01-3.18). A statistically significant increase in the risk of colon cancer was associated with increasing coffee consumption among men (P for trend = 0.03). On the other hand, coffee consumption in women was not associated with incident risk of colon cancer. Coffee consumption was also not associated with rectal cancer incidence in men or women. CONCLUSIONS: This large-scale population-based cohort study showed that coffee consumption increases the risk of colon cancer among Japanese men.

6-Methylsulfinylhexyl isothiocyanate modulates endothelial cell function and suppresses leukocyte adhesion.

6-Methylsulfinylhexyl isothiocyanate (6-MSITC) is an active compound in wasabi (Wasabia japonica Matsum.), which is one of the most popular spices in Japan. 6-MSITC suppresses lipopolysaccharide-induced macrophage activation, arachidonic- or adenosine diphosphate-induced platelet activation, and tumor cell proliferation. These data indicate that 6-MSITC has several biological activities involving anti-inflammatory, anti-coagulant, and anti-apoptosis properties. Endothelial cells (ECs) maintain vascular homeostasis and play crucial roles in crosstalk between blood coagulation and vascular inflammation. In this study, we determined the anti-coagulant and anti-inflammatory effects of 6-MSITC on human umbilical vein endothelial cells (HUVECs). 6-MSITC slightly reduced tissue factor expression, but did not alter von Willebrand factor release in activated HUVECs. 6-MSITC modulated the generation of activated protein C, which is essential for negative regulation of blood coagulation, on normal ECs. In addition, 6-MSITC reduced tumor necrosis factor-α (TNF-α)-induced interleukin-6 and monocyte chemoattractant protein-1 expression. 6-MSITC markedly attenuated TNF-α-induced adhesion of human monoblast U937 cells to HUVECs and reduced vascular cell adhesion molecule-1 and E-selectin mRNA expression in activated ECs. These results showed that 6-MSITC modulates EC function and suppresses cell adhesion. This study provides new insight into the mechanism of the anti-inflammatory effect of 6-MSITC, suggesting that 6-MSITC has therapeutic potential as a treatment for vasculitis and vascular inflammation.

Amla (Emblica officinalis Gaertn.) extract inhibits lipopolysaccharide-induced procoagulant and pro-inflammatory factors in cultured vascular endothelial cells.

Amla (Emblica officinalis Gaertn.) has been used for many centuries in traditional Indian Ayurvedic formulations for the prevention and treatment of many inflammatory diseases. The present study evaluated the anti-inflammatory and anticoagulant properties of amla fruit extract. The amla fruit extract potentially and significantly reduced lipopolysaccharide (LPS)-induced tissue factor expression and von Willebrand factor release in human umbilical vein endothelial cells (HUVEC) in vitro at clinically relevant concentrations (1-100 µg/ml). In a leucocyte adhesion model of inflammation, it also significantly decreased LPS-induced adhesion of human monocytic cells (THP-1) to the HUVEC, as well as reduced the expression of endothelial-leucocyte adhesion molecule-1 (E-selectin) in the target cells. In addition, the in vivo anti-inflammatory effects were evaluated in a LPS-induced endotoxaemia rat model. Oral administration of the amla fruit extract (50 mg/kg body weight) significantly decreased the concentrations of pro-inflammatory cytokines, TNF-α and IL-6 in serum. These results suggest that amla fruit extract may be an effective anticoagulant and anti-inflammatory agent.

Antibacterial activity of phytochemicals isolated from Atractylodes japonica against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide as one of the most important problems in communities and hospitals. Therefore, new agents are needed to treat acute oral infections from MRSA. In this study, antibacterial compounds from the roots of Atractylodes japonica (A. japonica) were isolated and characterized. The compounds were isolated from the root extracts using HPLC-piloted activity-guided fractionations. Four A. japonica compounds were isolated and identified as atractylenolide III (1), atractylenolide I (2), diacetylatractylodiol [(6E,12E)-tetradeca-6,12-diene-8,10-diyne-1,3-diol diacetate, TDEYA, 3). and (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (TDEA, 4), which was obtained by hydrolysis of TDEYA. The minimum inhibitory concentrations (MICs) was determined in the setting of clinical MRSA isolates. Compound 4 showed anti-MRSA activity with a MIC value of 4-32 µg/mL. The overall results provide promising baseline information for the potential use of the extract of A. japonica as well as some of the isolated compounds in the treatment of bacterial infections.

Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons.

Excess administration of glutamate is known to induce Ca(2+) overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg(2+) in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg(2+) in the excitotoxicity, we simultaneously measured intracellular Ca(2+) and Mg(2+), using fluorescent dyes, Fura red, a fluorescent Ca(2+) probe, and KMG-104, a highly selective fluorescent Mg(2+) probe developed by our group, respectively. Administration of 100 µM glutamate supplemented with 10 µM glycine to rat hippocampal neurons induced an increase in intracellular Mg(2+) concentration ([Mg(2+)](i)). Extracellular Mg(2+) was not required for this glutamate-induced increase in [Mg(2+)](i), and no increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) or [Mg(2+)](i) was observed in neurons in nominally Ca(2+)-free medium. Application of 5 µM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca(2+)](i) and [Mg(2+)](i). Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg(2+)](i) but did induce an additive increase in [Ca(2+)](i). Moreover, the glutamate-induced increase in [Mg(2+)](i) was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg(2+) efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca(2+) uniporter, prevented this [Mg(2+)](i) increase. These results indicate that glutamate-induced increases in [Mg(2+)](i) result from the Mg(2+) release from mitochondria and that Ca(2+) accumulation in the mitochondria is required for this Mg(2+) release.

An in vitro method for screening anti-platelet agents using a microchannel array flow analyzer.

New in vitro methods are desirable for the analysis of platelet aggregation and screening novel anti-platelet agents using whole blood. To this end, we examined platelet aggregation and thrombus formation in whole human blood from healthy volunteers using a microchannel array flow analyzer (MC-FAN). Platelet aggregation in whole blood, treated with the activating agents ADP, collagen or ristocetin was detected in the MC-FAN by measuring the decrease in flow rate as a function of agent concentration. The results were compared with aggregation in platelet rich plasma (PRP) in a conventional aggregometer, as measured by the increase in optical density. The MC-FAN detected platelet aggregation in whole blood at two- to four-fold lower concentrations of agonist compared to those in PRP in the aggregometer. Anti-platelet agents attenuated the decrease in blood flow rate in the MC-FAN by inhibiting fibrin formation and platelet aggregation, but anticoagulants only inhibited fibrin formation and did not affect blood flow rates. These findings suggest that the MC-FAN system may be a useful method for the evaluation of platelet activation and facilitate the development of novel anti-platelet agents.

Inhibitions of urinary oxidative stress and renal calcium level by an extract of Quercus salicina Blume/Quercus stenophylla Makino in a rat calcium oxalate urolithiasis model.

OBJECTIVES: To clarify the mechanism of Urocalun, an extract of Quercus salicina Blume/Quercus stenophylla Makino (QS), in the treatment of urolithiasis. METHODS: Rat calcium oxalate urolithiasis was induced by oral administration of ethylene glycol and the vitamin D3 analog alfa-calcidol for 14 days. QS extract was repeatedly given to rats. After the last administration, biochemistries in urine and plasma, renal calcium, and urinary malondialdehyde (an oxidative stress marker) were measured. RESULTS: Ethylene glycol and alfa-calcidol treatment increased urinary malondialdehyde and renal calcium levels. This increase was significantly suppressed by the administration of QS extract, suggesting that the inhibition of renal calcium accumulation by QS extract is due to its antioxidative activity. CONCLUSIONS: These findings suggest that the antioxidative activity of QS extract plays a role in the prevention of stone formation and recurrence in urolithiasis.

Reduction in oxalate-induced renal tubular epithelial cell injury by an extract from Quercus salicina Blume/Quercus stenophylla Makino.

Urocalun, a herbal medicine prepared from an extract of Quercus salicina Blume/Quercus stenophylla Makino (QS extract), has been clinically used for the treatment of urolithiasis in Japan since 1969. In the present study, the effects of QS extract on oxalate-induced cell injury and NADPH-induced superoxide anion (O(2) (-)) production in the injured cells were investigated. Oxalate-induced cell injury was assessed by mitochondrial reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyltetrazolium bromide and leakage of lactate dehydrogenase into the extracellular fluid. When NRK-52E cells were injured by exposure to oxalate for 24 h, QS extract prevented the injury in a dose-dependent manner. In addition, QS extract suppressed the increase in NADPH-induced O(2) (-) production, or NADPH oxidase activity, in the homogenate of cells injured by oxalate exposure. These findings suggest that the reduction in oxalate-induced O(2) (-) production contributes to the cytoprotective effect of QS extract.

Effects of oxalate exposure on Madin-Darby canine kidney cells in culture: renal prothrombin fragment-1 mRNA expression.

It has been suggested that renal tubular cell damage induced by oxalic acid, one of the components of urinary calculi, may be involved in a variety of ways in the development of urolithiasis. During our study on a calculus related protein, renal prothrombin fragment-1 (RPTF-1), we noted that this is an inflammation related substance that mediates an acute inflammatory reaction, one of the original roles of prothrombin. RPTF-1 is a part of prothrombin that is a coagulation factor known to be expressed in the renal tubule. We examined whether oxalic acid may cause cytotoxic effects on tubular epithelial cells and whether such chemical stimulation may promote the translation of RPTF-1 mRNA into RPTF-1 proteins. We used Madin-Darby canine kidney (MDCK) cells derived from the distal tubule of a dog kidney. In this study, the effects of oxalic acid in culture solution at different concentrations on cytotoxicity were assessed using a MTT assay. The location of active oxygen species was identified using dichlorofluorescein diacetate. After the prothrombin sequence of RPTF-1 was confirmed in MDCK cells, RPTF-1 mRNA expression was determined by RT-PCR. The gene sequence of the same promoter area was ligated, and a luciferase sequence was inserted downstream of the vector. The target sequence was transfected into MDCK cells and the relation between oxalic acid and prothrombin promoter was examined. In addition, the variable expression of RPTF-1 mRNA was quantitatively compared depending on oxalic acid concentrations using real-time PCR. When cytotoxicity was investigated, cells were not damaged but, by contrast, were stimulated and activated under oxalic acid below a certain concentration. The relation between cytotoxicity on the cultured MDCK cell membrane and active oxygen species was confirmed. Luminescence in MDCK cells containing the luciferase gene was detected by the addition of oxalic acid, which activated the prothrombin promoter. A part of the prothrombin gene sequence in the MDCK cells was detected and an increase in the expression of RPTF-1 mRNA in MDCK cells by the addition of oxalic acid was confirmed using real-time PCR. Increased expression of prothrombin by adding oxalic acid has already been demonstrated in previous studies. In this study, however, RPTF-1 mRNA was promoted by oxalic acid and a direct association between oxalic acid and RPTF-1 is indicated. This finding shows that increased oxalic acid in urine induces the expression of RPTF-1 in tubular epithelial cells and thereby causes the generation of active oxygen species.

Association of serum phytoestrogen concentration and dietary habits in a sample set of the JACC Study.

BACKGROUND: Phytoestrogens may be associated with a reduced risk of hormone dependent neoplasms such as prostate and breast cancers. We tried to determine the validity of the association between serum phytoestrogen concentrations and dietary habits obtained from a food frequency questionnaire used in the Japan Collaborative Cohort Study (JACC Study) for Evaluation of Cancer Risk sponsored by the Ministry of Education, Science, Sports and Culture of Japan (Monbusho). METHODS: The subjects were 151 male controls who were selected for a nested case-control study for evaluating prostate cancer risk as part of the JACC Study. Dietary habits were determined using a food frequency questionnaire at baseline, and the concentrations of genistein, daidzein, and equol in frozenstored serum samples assayed in 2002 were compared. RESULTS: Tofu intake showed a significant association with the serum concentrations of genistein and daidzein (Spearman's correlation coefficients (rs)=0.30 and 0.27, respectively), and miso soup showed a slight association with serum concentrations of these phytoestrogens. In contrast, serum concentrations of equol were not associated with dietary intake of tofu and miso soup. After adjustment for serum daidzein concentration, serum equol concentration was associated with the intake of foods containing fat, meat, and coffee, but not green tea. CONCLUSIONS: Serum genistein and daidzein concentrations were significantly associated with dietary intake of tofu, and slightly with intake of miso soup. Consumption of fat, meat, and coffee may be associated with equol production by intestinal microflora in this sample set.

Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment.

BACKGROUND: We investigated whether the improvement of cardiac function and remodeling after myocardial infarction (MI) by granulocyte colony-stimulating factor (G-CSF) relates to acceleration of the healing process, in addition to myocardial regeneration. METHODS AND RESULTS: In a 30-minute coronary occlusion and reperfusion rabbit model, saline (S) or 10 microg x kg(-1) x d(-1) of human recombinant G-CSF (G) was injected subcutaneously from 1 to 5 days after MI. Smaller left ventricular (LV) dimension, increased LV ejection fraction, and thicker infarct-LV wall were seen in G at 3 months after MI. At 2, 7, and 14 days and 3 months after MI, necrotic tissue areas were 14.2+/-1.5/13.4+/-1.1, 0.4+/-0.1/1.8+/-0.5*, 0/0, and 0/0 mm2 x slice(-1) x kg(-1), granulation areas 0/0, 4.0+/-0.7/8.5+/-1.0*, 3.9+/-0.8/5.7+/-0.7,* and 0/0 mm2 x slice(-1) x kg(-1), and scar areas 0/0, 0/0, 0/0, and 4.2+/-0.5/7.9+/-0.9* mm2 x slice(-1) x kg(-1) in G and S, respectively (*P<0.05, G versus S). Clear increases of macrophages and of matrix metalloproteinases (MMP) 1 and 9 were seen in G at 7 days after MI. This suggests that G accelerates absorption of necrotic tissues via increase of macrophages and reduces granulation and scar tissues via expression of MMPs. Meanwhile, surviving myocardial tissue areas within the risk areas were significantly increased in G despite there being no difference in LV weight, LV wall area, or cardiomyocyte size between G and S. Confocal microscopy revealed significant increases of cardiomyocytes with positive 3,3,3',3'-tetramethylindocarbocyanine perchlorate and positive troponin I in G, suggesting enhanced myocardial regeneration by G. CONCLUSIONS: The acceleration of the healing process and myocardial regeneration may play an important role for the beneficial effect of post-MI G-CSF treatment.

Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men.

The purpose of this study was to examine whether a high serum concentration of phytoestrogens reduces the risk of prostate cancer in a case-control study nested in a community-based cohort in Japan (Japan Collaborative Cohort (JACC) Study). Information on lifestyles and sera of the subjects were collected in 1988-90, and they were followed up to 1999. Incident and dead cases of prostate cancer and controls were matched for study area and age. Phytoestrogens and sex hormones in sera stored at - 80 degrees C were measured in 2002. Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified. Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after excluding subjects with low testosterone levels who were suspected of having had medical intervention, and 3) 28 cases and 69 controls with prostate specific antigen level of