FNDC5/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory.

As a passive motion and non-invasive treatment, theta-shaking exercise is considered an alternative to traditional active exercise for slowing down brain ageing. Here, we studied the influence of theta-shaking exercise on fibronectin type III domain containing 5/irisin (FNDC5/irisin) in the anterior nucleus of the thalamus, hippocampus, and medial prefrontal cortex (ATN-HPC-MPFC). Further, we assessed memory in senescence-accelerated prone mice (SAMP-10 mice) using a behavioural test to confirm the protective effect of theta-shaking exercise against age-related memory decline. SAMP-10 mice were subjected to theta-shaking exercise for 9-30 weeks. Mice then performed the T-maze test and passive avoidance task. Immunohistochemical analysis and ELISA were used to assess FNDC5/irisin, nerve growth factor (NGF), and neurotrophin 4/5 (NT4/5) expression in the ATN-HPC-MPFC. In the shaking group, FNDC5 was locally upregulated within the hippocampus and MPFC area rather than exhibiting even distribution throughout brain tissue. Irisin levels were generally higher in the control group. Meanwhile, hippocampal NGF levels were significantly higher in the shaking group, with no differences noted in neurotrophin levels. Theta-shaking preserved normal neurons in certain sub-regions. However, no beneficial changes in neuronal density were noted in the ATN. Theta-shaking exercise positively affects memory function in SAMP-10 mice. FNDC5 upregulation and higher levels of NGF, along with the potential involvement of irisin, may have contributed to the preservation of normal neuronal density in the hippocampus and MPFC subregions.

Exercise through Shaking Stimuli Suppresses Cancer Growth via the Wnt pathway in ApcMin/+ Mice.

OBJECTIVE: Exercise has been reported to suppress colorectal cancer; however, the mechanism of suppression by exercise and its effect on the Wnt pathway, which is particularly involved in the early stage of carcinogenesis, remain unclear. In this study, we subjected ApcMin/+ mice to exercise by shaking stimuli to investigate the mechanisms of suppressing colorectal cancer, and focused on the Ca2+ pathway, which is one of the ß-catenin-independent Wnt signaling pathways that suppress the accumulation of ß-catenin. METHODS: Mice in the exercise group were subjected to exercise by shaking stimuli for 30 min/session, 6 sessions/ week, for a total of 11 weeks. The number and diameter of intestinal polyps were calculated. Expression analysis of ß-catenin and Pak1 from the intestinal tract and Wnt5a-Pan and Wnt5a-Long from the gastrocnemius muscle was performed by western blotting. The expression of ß-catenin and Wnt5a-Pan was observed by immunohistochemical staining. RESULT: The levels of expression of ß-catenin and Pak1 in the small intestine were low in the exercise group, indicating that exercise suppressed the accumulation of ß-catenin. In the gastrocnemius muscle, the levels of expression of Wnt5a-Pan and Wnt5a-Long were significantly higher in the exercise group (p < 0.05). Histological analysis revealed that the percentage of large polyps was significantly lower in the exercise group than in the control group (p < 0.01), revealing that exercise suppressed the growth of polyps. In addition, the villi/crypt ratio (V/C ratio) was significantly higher in the exercise group, suggesting the suppression of exercise-induced local inflammation in the small intestine. CONCLUSION: We believe that the mechanism of polyp growth suppression is related to the inflammatory and not the Wnt pathway. This study clarified the growth-suppressing effect of a novel exercise method on cancer. We believe that its development and clinical application might open new possibilities for the prevention treatment of colorectal cancer.

Novel shaking exercises for hippocampal and medial prefrontal cortex functioning maintain spatial working memory.

INTRODUCTION: The decline in spatial working memory is one of the earliest signs of normal brain aging. OBJECTIVE: We developed a novel physical exercise method, termed the "shaking exercise," to slow down this process. METHODS: The experimental protocol included administering the shaking exercise for 8-32 weeks in male senescence-accelerated mouse prone 10 (SAMP-10). They were subjected to the T-maze test, followed by immunohistochemical analysis, to assess the influence of the shaking exercise on the M1 muscarinic acetylcholine receptor (CHRM1) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) of the dorsal hippocampus and medial prefrontal cortex (dHC-mPFC). RESULTS: The T-maze test demonstrated that the shaking group had less hesitation in the face of selecting direction at week 24. In the immunohistochemical analysis, more CHRM1s were in the CA3 subregion and more AMPARs were in the subiculum. CHRM1s and AMPARs were maintained in the CA1 region and the mPFC. The CHRM1s seem to have a positive effect on the AMPAR in the dentate gyrus (DG) region and the CA3 region. In the CA1 region, CHRM1s were negatively correlated with AMPARs. In addition, high-density neurons were expressed in the shaking group in the upstream DG, the middle part and the distal part of CA3, the distal part of CA1, and the mPFC. CONCLUSIONS: Our results raise the possibility that maintenance of the spatial working memory effect observed with the shaking exercise is driven in part by the uneven affection of CHRM1s and AMPARs in the dHC-mPFC circuit system and significantly maintains the neuronal expression in the dHC-mPFC.

Exercise by Shaking Alleviates the Decline in Memory due to Aging: A Study in Mice.

INTRODUCTION: Although exercise can prevent cognitive decline due to aging, few elderly individuals are able to exercise for long. Therefore, an exercise method for older adults that is feasible for a long duration without overexertion is necessary. In this study, we focused on exercise by shaking. This study examined the possibility to prevent the decline in memory through regular and long-term shaking exercise using a senescence-accelerated mouse (SAM) model. Behavioral analysis was conducted, and histological changes in the mouse brain were examined to evaluate whether this stimulation method could become a novel exercise method. MATERIALS AND METHODS: The shaking exercise was applied to SAMP10 mice for 30 min 3 times per week for 25 continuous weeks. Behavioral analysis included a step-through passive avoidance test, whereas the histological analysis involved immunohistochemical staining using the anti-glutamate receptor (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors [AMPAR]) antibody in the hippocampus. The number and area of nerve cells in the hippocampal regions were measured and compared between groups. RESULTS: Behavioral analysis revealed that the shaking group retained memory longer than the control group, and memory capacity decline was suppressed. Additionally, histological examination showed that the shaking group had a higher number of AMPAR receptor-positive neurons per area in the hippocampal CA1 and CA3 regions than the control group, suggesting that degeneration and shedding of neurons due to aging was suppressed. DISCUSSION/CONCLUSION: We believe that shaking could become an exercise therapy that can reduce the decline in memory with aging and expect its human application in the future.

A case of planar-type gastrointestinal stromal tumor of the transverse colon with perforation.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the human gastrointestinal tract. They usually develop in the stomach and small intestine, but extremely rarely in the colon. Although most GISTs form a mass, some cases showing a flatly proliferating lesion called planar-type GIST have been reported in the sigmoid colon and small intestine. Those are often associated with diverticular lesion and/or perforation. We present here a case of planar-type GIST of the transverse colon with perforation. A 49-year-old Japanese woman abruptly complained of abdominal pain, and was clinically diagnosed as perforation of the transverse colon. Partial resection of the transverse colon including the perforated site was done, and no apparent mass lesion was present. Histology showed that spindle cells flatly proliferated around the perforated area and replaced the layers from submucosa to subserosa. Immunohistochemistry revealed that the spindle cells were KIT-, DOG1- and CD34-positive. Codons 557 and 558 of exon 11 of the c-kit gene were heterozygously deleted at the lesional tissue but not at the normal mucosal tissue. Planar-type GIST of the transverse colon has not been reported yet, and the literature search for the similar cases was done.

Avoiding the incompatibility of peripheral parenteral nutrition solution and midazolam injection for intravenous sedation.

OBJECTIVES: We have observed white turbidity when a midazolam injection is administered from a lateral tube during the administration of a peripheral parenteral nutrition (PPN) solution. The aim of the current study was to determine how to avoid compound changes when co-administering a midazolam injection and a PPN solution. METHODS: Midazolam solutions were prepared by diluting a midazolam injection with a 5% glucose intravenous infusion. We examined the formulation of the midazolam injection and a PPN solution at the concentrations used in a clinical setting for changes in appearance, pH, and midazolam content in test tubes and during administration conditions. RESULTS: With a 1/4.8 dilution of midazolam in undiluted solution, clouding occurred. A strong correlation was revealed between the midazolam content as measured through high-performance liquid chromatography and the mixture's midazolam concentration (R2=0.9918). The capture rate of midazolam infused with PPN solution was 91.0% at a 1/6 dilution, whereas it decreased to <90% at a 1/4.8 dilution. CONCLUSIONS: Our results suggest that the administration of a midazolam injection solution diluted by ≥6-fold with glucose solution or saline from a side tube during the administration of a PPN solution did not cause changes in composition.

Influence of muscle mass on the estimation of glomerular filtration rate in Japanese terminal cancer patients.

BACKGROUND: Estimated glomerular filtration rate (eGFR) based on serum cystatin C (Scys) is useful for patients with decreased muscle mass, but has been also reported to be affected by cancer. The usefulness of Scys in eGFR in terminal cancer patients with decreased muscle mass is unknown. Therefore, we analyzed appropriate eGFR formulae for terminal cancer patients. METHODS: Study design was a retrospective observational study. Based on creatinine height index (CHI), 184 terminal cancer patients were stratified into CHI ≥ 90% (normal muscle mass, 59 patients); CHI 60-89% (mildly to moderately decreased muscle mass, 64 patients); and CHI < 60% (severely decreased muscle mass, 61 patients) groups. Twenty-four-hour creatinine clearance was measured and converted to the glomerular filtration rate (GFR) as a renal function measure. To estimate GFR, various eGFR formulae for Japanese were used: eGFRScys, eGFRScr5 and eGFRScr3, eGFRaverage and eGFRScys-Scr, and eGFRCG, based on Scys, serum creatinine (Scr), Scys and Scr combined, and Cockcroft-Gault formula (CG), respectively. Errors between measured and estimated values of renal function were verified using mean prediction errors (ME). When a 95% confidence interval (CI) of ME included 0, the accuracy of the eGFR formula was graded as good. RESULTS: eGFRScys ME was 0.2 (95% CI lower limit - 3.7, upper limit 4.0) mL/min/1.73 m2 in CHI 60-89% group and 9.2 (6.1, 12.9) mL/min/1.73 m2 in CHI < 60% group. eGFRScys was most accurate among the eGFR formulae. CONCLUSIONS: eGFR based on Scys was demonstrated as useful in terminal cancer patients with decreased muscle mass.

Interleukin-8 and clinical symptoms can be prognostic indicators for advanced cancer patients with cachexia.

OBJECTIVES: Prognostic prediction is a significant tool for selecting appropriate treatment in advanced cancer patients with cachexia, at a time when it is important to offer high-quality palliative care and improve quality of life until death. In this retrospective study, we investigated the prognostic potential of serum cytokine level and various clinical symptoms by analyzing the pathological conditions and metabolic dynamics of cachexia in advanced cancer patients. METHODS: One hundred and fifty-three advanced cancer patients who underwent palliative care and died at the Department of Surgery and Palliative Medicine, Fujita Health University Nanakuri Memorial Hospital between 1 January 2004 and 30 June 2007 were eligible for the study. We simultaneously assessed their blood factors and clinical symptoms at admission. All patients were divided into two groups according to median survival time to analyze the risk factors for prognosis. RESULTS: Multivariate analysis revealed the following independent prognostic factors: interleukin (IL)-8 (odds ratio [OR]=4.17, 95% confidence interval [CI]=1.52-11.41, p=0.002), general fatigue (OR=1.22, 95%CI=1.03-1.45, p=0.019), anorexia (OR=1.19, 95%CI=1.04-1.37, p=0.008), dyspnea (OR=1.19, 95%CI=1.02-1.38, p=0.024), depression (OR=1.28, 95%CI=1.11-1.47, p<0.001), nausea (OR=1.25, 95%CI=1.05-1.48, p=0.007), dry mouth (OR=1.19, 95%CI=1.01-1.40, p=0.032), and overall assessment score (OR=1.05, 95%CI=1.02-1.09, p<0.001). Patients with low IL-8 (<1.347 pg/ml) and low overall assessment score (<26) had significantly better prognosis (both p<0.0001). CONCLUSIONS: High IL-8 level and clinical symptoms can be prognostic indicators for advanced cancer patients with cachexia.

Effects of Combined Treatment with Branched-Chain Amino Acids, Citric Acid, L-Carnitine, Coenzyme Q10, Zinc, and Various Vitamins in Tumor-Bearing Mice.

A functional dietary supplement (FDS) containing Coenzyme Q10, branched-chain amino acids and L-carnitine was administered to tumor-bearing mice, investigating its effects on tumor and muscle tissues. Experiment (A): B16 melanoma cells were implanted subcutaneously into the right side of the abdomen of 8- to 9-week-old C57BL/6J mice. The mice were divided into two groups: a FDS group that received oral administration of FDS (n=10), and a control group that received oral administration of glucose (n=10). The moribund condition was used as the endpoint, and median survival time was determined. Experiment (B): On day 21 after tumor implantation, tumors, soleus muscle, gastrocnemius muscle, and suprahyoid muscles were collected. Tumor and muscle weight and other aspects were evaluated in each group: FDS group (n=15) and control group (n=15). The median survival time was comparable (21 d in the FDS group vs. 18 d in the control group, p=0.30). However, cumulative food intake was significantly higher in the FDS group than the control group (p=0.011). Metastasis of melanoma to the lung was observed in the control group but not in the FDS group (p=0.043). The weight of the suprahyoid muscles was significantly higher in the FDS group than in the control group (p=0.0045). The weight of the tumor was significantly lower in the FDS group than in the control group (p=0.013). The results possibly suggest oral administration of FDS in tumor-bearing mice enhances the maintenance of suprahyoid muscles, resulting in an extended feeding period and suppression of tumor growth and metastasis.

A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids.

There have been few detailed reports on respiratory depression due to overdoses of opioids in terminal cancer patients. We investigated the situation of treatment with opioid antagonists for respiratory depression that occurred after administration of opioid at optimal doses in terminal cancer patients, to clarify pathological changes as well as causative factors. In 2443 terminal cancer patients receiving opioids, 7 patients (0.3%) received opioid antagonists: 6, morphine (hydrochloride, 5; sulfate, 1); 1, oxycodone. The median dosage of opioids was 13.3 mg/d, as converted to morphine injection. Respiratory depression occurred on this daily dose in 4 patients and after changed dose and route in 3 patients. Opioids were given through the vein in 6 patients and by the enteral route in 1 patient. Concomitant drugs included nonsteroidal anti-inflammatory drugs in 3 patients and zoledronic acid in 2 patients. In morphine-receiving patients, renal functions were significantly worsened at the time of administration of an opioid antagonist than the day before the start of opioid administration. These findings indicate that the proper use of opioids was safe and acceptable in almost all terminal cancer patients. In rare cases, however, a risk toward respiratory depression onset is indicated because morphine and morphine-6-glucuronide become relatively excessive owing to systemic debility due to disease progression, especially respiratory and renal dysfunctions. At the onset of respiratory depression, appropriate administration of an opioid antagonist mitigated the symptoms. Thereafter, opioid switching or continuous administration at reduced dosages of the same opioids prevented the occurrence of serious adverse events.

[A Case of Liver Metastasis from Colorectal Cancer That Showed a Pathological Complete Response to mFOLFOX6 plus Cetuximab].

A 68-year-old man was diagnosed with rectal cancer on colonoscopy and liver metastasis of rectal cancer on abdominal computed tomography(CT). He underwent resection of the primary lesion, and the final diagnosis was A, N1, H1, P0, M0, fStage IV. After resection of the primary lesion, he received chemotherapy with mFOLFOX6 plus cetuximab. After 6 courses of the treatment, CT revealed partial response of the liver metastasis. Then, he underwent resection of the liver metastasis. The pathological finding revealed that the resected specimen had no cancer cells. After resection of the liver metastasis, he received 6 courses of chemotherapy with the same regimen, and relapse-free survival continues until the time of this writing.

Effects of exercise and bryostatin-1 on serotonin dynamics after cerebral infarction.

Although it has been suggested that the combination of exercise and bryostatin-1 administration may induce greater functional recovery than exercise alone, the detailed molecular mechanisms are not well known. Here, we examined the relationship between this combination treatment and monoamine dynamics in the cerebral cortex peri-infarction area to promote our understanding of these molecular mechanisms. Experimental cerebral cortex infarctions were produced by photothrombosis in rats. Voluntary exercise was initiated 2 days after surgery. Motor performance was then measured using the rotarod test. Monoamine concentrations in the perilesional cortex were analyzed by high-performance liquid chromatography. In behavioral evaluations, performance in the rotarod test was significantly increased by exercise. Moreover, performance in the rotarod test after the combination of exercise and bryostatin-1 administration was significantly greater than that after exercise alone. In the analysis of monoamines, serotonin (5-HT) concentrations were significantly higher in the groups treated with exercise and bryostatin-1. In addition, 5-HT turnover was significantly lower in the groups treated with exercise and bryostatin-1. Furthermore, the mean latency in the rotarod test showed a significant positive correlation with 5-HT levels. In immunohistochemical analysis, 5-HT immunoreactivity in the dorsal raphe nucleus was shown to be higher in the groups treated with exercise. In the present study, we detected changes in the levels of monoamines associated with the combined treatment of exercise and bryostatin-1 administration in the perilesional cortex. It has been suggested that this combination of therapies may affect 5-HT turnover and serve to increase local 5-HT concentrations in the perilesional area.

Inhibition of Azoxymethane-induced Colorectal Aberrant Crypt Foci in Mice Fed a High-fat Diet by Pleurotus eryngii (Eringi) and Hypsizygus marmoreus (Bunashimeji).

Obesity markedly increases the risk of colorectal cancer. Recently, the preventive effects of edible mushrooms on triglyceride elevation and visceral fat accumulation have been reported. Here, the effects of Pleurotus eryngii (Eringi) and Hypsizygus marmoreus (Bunashimeji) on azoxymethane (AOM)-induced aberrant crypt foci (ACF; precancerous lesions) in the colorectums of mice fed a high-fat diet were examined. Eringi (ER) and Bunashimeji (BU) mushroom powder samples were used. Six-week-old male C57BL/6J mice received an intraperitoneal injection of AOM (10 mg/kg) once a week for two weeks, and were sacrificed and dissected at 6 weeks after the start of the experiment. After the initiation of the experiment, they received a normal diet (ND), high-fat diet (HFD), HFD + ER (1 or 5% of diet), or HFD + BU (1 or 5% of diet). As a result, body and fat weights were significantly lower in the 5% ER and BU groups than in the HFD group. Liver triglyceride levels were also significantly lower in the 5% ER and BU groups. Total liver cholesterol levels were significantly lower in the 5% ER group. The numbers of ACF (especially large ACF) showed strong inhibitory effects in both ER and BU groups. Measurement of the cell proliferation marker Ki-67 labeling index in the colonic mucosa demonstrated more significant suppression in both ER and BU groups than in the HFD group. These results suggest that the simultaneous intake of ER and BU may inhibit colorectal tumorigenesis in HFD-fed mice.

Effects of Aloe-emodin and Emodin on Proliferation of the MKN45 Human Gastric Cancer Cell Line.

Aloe-emodin (1, 8-dihydroxy-3-hydroxyl-methylanthraquinone; AE) and emodin (1,3,8-trihydroxy-6- methylanthraquinone; EM) are anthraquinone derivatives that have been detected in some medical plants and share similar anthraquinone structures. AE and EM have been shown to exhibit anticancer activities in various cancer cell lines; however, the inhibitory effects of these derivatives on the growth of cancer cells were previously reported to be different. Gastric cancer is the second most common cause of cancer cell death worldwide. In the present study, we examined the inhibitory effects of 0.05 mM AE and 0.05 mM EM on the proliferation of the MKN45 human gastric cancer cell line. The proliferation of MKN45 cells was significantly inhibited in AE- and EM-treated groups 24 h and 48 h after treatment. Furthermore, the inhibitory effects of EM were stronger than those of AE. The cell cycle of MKN45 cells were arrested in G0/G1 phase or G0/G1 and G2/M phases by AE and EM, respectively. However, an analysis of intracellular polyamine levels and DNA fragmentation revealed that the mechanisms underlying cell death following cell arrest induced by AE and EM differed.

Dietary aloe vera gel powder and extract inhibit azoxymethane- induced colorectal aberrant crypt foci in mice fed a high- fat diet.

Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

Inhibitory effects of low-dose aloe-emodin on the development of colorectal tumors in min mice.

Aloe-emodin (AE), a natural anthraquinone compound, has been reported to exhibit anticancer activity in various cancer cell lines and anti-inflammatory effects in murine macrophages. In the present study, we investigated the cancer chemopreventive effects of AE in an Apc-deficient Min mouse model. In the first experiment, male Min mice were fed a basal diet or diets containing 5 ppm AE and 10 ppm AE for 12 weeks. The dietary administration of 5 ppm AE significantly reduced the number of colorectal tumors. In a second experiment, we investigated the effects of AE on colitis-related colon carcinogenesis in Min mouse treated with dextran sodium sulfate (DSS). Female Min mice were administered 1% DSS in their drinking water for 7 days. AE was given to mice in their diet at a dose of 5 or 50 ppm for 5 weeks. Feeding with AE significantly reduced the number of colorectal tumors. When proliferation of cells in normal-appearing colonic mucosa was assessed by monoclonal anti-rat Ki-67 antibody (MIB-5) immunohistochemistry in experiments 1 and 2, the AE treatment significantly decreased the mean MIB-5-labeling index. These results suggest that the dietary administration of low-dose AE may have chemopreventive effects against development of colorectal tumors in Min mice, possibly in part by reducing cell proliferation in colorectal mucosa.

Reduction of intestinal polyp formation in min mice fed a high-fat diet with aloe vera gel extract.

Aloe vera gel supercritical CO2 extract (AVGE) has been shown to contain five phytosterols, reduce visceral fat accumulation, and influence the metabolism of glucose and lipids in animal model experiments. Recent epidemiologic studies have shown that obesity is an established risk factor for several cancers including colorectal cancer. Therefore, we examined the effects of AVGE on intestinal polyp formation in Apc-deficient Min mice fed a high-fat diet. Male Min mice were divided into normal diet (ND), high fat diet (HFD), low dose AVGE (HFD+LAVGE) and high dose AVGE (HFD+HAVGE) groups. The ND group received AIN-93G diet and the latter 3 groups were given modified high-fat AIN-93G diet (HFD) for 7 weeks. AVGE was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally to mice in HFD+LAVGE and HFD+HAVGE groups every day (except on Sunday) for 7 weeks at a dose of 3.75 and 12.5 mg/kg body weight, respectively. ND and HFD groups received 0.5% CMC alone. Between weeks 4 and 7, body weights in the HFD and HFD+LAVGE groups were reduced more than those in the ND group. However, body weights were not reduced in the HFD+HAVGE group. Mice were sacrificed at the end of the experiment and their intestines were scored for polyps. No significant differences were observed in either the incidence and multiplicity of intestinal polyps (≥0.5 mm in a diameter) among the three groups fed HFD. However, when intestinal polyps were categorized by their size into 0.5-1.4, 1.5-2.4, or ≥2.5 mm, the incidence and multiplicity of large polyps (≥2.5 mm) in the intestine in the HFD+HAVGE group were significantly lower than those in the HFD group. We measured plasma lipid (triglycerides and total cholesterol) and adipocytokine [interleukin-6 and high molecular weight (HMW) adiponectin] levels as possible indicators of mechanisms of inhibition. The results showed that HMW adiponectin levels in the HFD group were significantly lower than those in the ND group. However, the levels in the HFD+HAVGE group were significantly higher than those in the HFD group. These results indicate that HAVGE reduced large-sized intestinal polyps and ameliorated reduction in plasma HMW adiponectin levels in Min mice fed HFD.

Effects of exercise after focal cerebral cortex infarction on basal ganglion.

Identification of functional molecules in the brain related to improvement of motor dysfunction after stroke will contribute to establish a new treatment strategy for stroke rehabilitation. Hence, monoamine changes in basal ganglion related to motor control were examined in groups with/without voluntary exercise after cerebral infarction. Cerebral infarction was produced by photothrombosis in rats. Voluntary exercise using a running wheel was initiated from 2 days after surgery. Motor performance was measured by the accelerated rotarod test. Monoamine concentrations in striatum were analyzed using HPLC and immunohistochemical staining performed with anti-tyrosine hydroxylase antibody. In behavioral evaluation, the mean latency until falling from the rotating rod in the group with exercise (infarction-EX group) was significantly longer than that in the group without exercise (infarction-CNT group). When concerning the alteration of monoamine concentration between before and 2 days after infarction, dopamine level showed a significant increase 2 days after infarction. Subsequently, dopamine level was significantly decreased in the infarction-EX group at 10 days after infarction; in contrast, both norepinephrine and 5-HT concentrations were significantly higher in the infarction-EX group than in the infarction-CNT group. Furthermore, duration of rotarod test showed a significant inverse correlation with dopamine levels and a significant positive correlation with 5-HT levels. In immunohistochemical analysis, tyrosine hydroxylase immunoreactivity in substantia nigra pars compacta was shown to increase in the infarction-CNT group. In the present study, at least some of the alterations of monoamines associated with the improvement of paralysis in the basal ganglion related to motor control might have been detected.

Experimental Research on Stimulation of Wound Healing by n-3 Fatty Acids.

UNLABELLED: Objexctive. The objective of this study was to investigate the wound healing effects of n-3 fatty acids and to identify factors that stimulate wound healing. MATERIALS AND METHODS: Four-week-old male Wistar rats were subjected to full-thickness skin wounds and assigned to 3 experimental diet groups (an n-3 fatty acid-fortified diet, a diet with a 1:3 ratio of n-3 to n-6 fatty acids, and an n-6 fatty acid-fortified diet). Intergroup comparisons were conducted for the changes in wound areas, the number of days to wound healing, and blood cytokines, blood hydroxyproline, and blood chemistry test values on the day before and after wound healing. RESULTS: The number of days to wound healing in the n-3/n-6 fatty acid group (18.4 ± 1.8 days) was significantly shorter than in the n-3 fatty acid-fortified diet (21.6 ± 1.6 days) and n-6 fatty acid-fortified diet groups (21.9 ± 1.8 days). This suggests that the n-3/n-6 fatty acid diet stimulates wound healing (P < 0.05). Changes in wound area, however, were not significantly different. The n-3 fatty acid-fortified diet was found to have potent immunopotentiating and anti-inflammatory effects in the group receiving this diet, as evidenced by total blood lymphocyte count and plasma levels of interleukin-1 beta (IL-1ß) and sialic acid on day 1 after wounding. The plasma hydroxyproline concentrations noted in the groups with a diet containing n-3 fatty acids indicate that this fatty acid type stimulates wound healing. CONCLUSIONS: Findings suggest that n-3 fatty acids have anti-inflammatory and immunopotentiating effects, and are beneficial in the wound healing process, particularly during early inflammation. .

Inhibition of ENNG-induced pyloric stomach and small intestinal carcinogenesis in mice by high temperature- and pressure-treated garlic.

High temperature- and pressure-treated garlic (HTPG) has been shown to have enhanced antioxidative activity and polyphenol contents. Previously, we reported that HTPG inhibited 1,2-dimethylhydrazine-induced mucin depleted foci (premalignant lesions) and O6-methylguanine DNA adduct formation in the rat colorectum. In the present study, we investigated the modifying effects of HTPG on N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)- induced pyloric stomach and small intestinal carcinogenesis in mice. Male C57BL/6 mice were given ENNG (100 mg/l) in drinking water for the first 4 weeks, then a basal diet or diet containing 2% or 5% HTPG for 30 weeks. The incidence and multiplicity of pyloric stomach and small intestinal (duodenal and jejunal) tumors in the 2% HTPG group (but not in the 5% HTPG group) were significantly lower than those in the control group. Cell proliferation of normal-appearing duodenal mucosa was assessed by MIB-5 immunohistochemistry and shown to be significantly lower with 2% HTPG (but again not 5% HTPG) than in controls. These results in dicate that HTPG, at 2% in the diet, inhibited ENNG-induced pyloric stomach and small intestinal (especially duodenal) tumorigenesis in mice, associated with suppression of cell proliferation.