Effectiveness of Repetitive Facilitative Exercise Combined with Electrical Stimulation Therapy to Improve Very Severe Paretic Upper Limbs in with Stroke Patients: A Randomized Controlled Trial.

Background: The difference in the effects of combined therapy with repetitive facilitative exercise (RFE) and neuromuscular electrical stimulation (NMES) on stroke upper limb paralysis was only reported by a pilot study; it has not been investigated in many patients. Objective: We investigated the effect of combined therapy with RFE and NMES on stroke patients with severe upper paresis. Methods: This study included 99 of the very severe paresis stroke patients with scores of zero or 1a in the Finger-Function test of the Stroke Impairment Assessment Set (SIAS). We randomly divided the patients into four groups, namely, NMES, RFE, RFE under NMES, and conventional training (CT) groups. A total of 20 min of group-specific training in addition to 40 min of conventional exercise per day, seven times a week for 4 weeks after admission, was performed. The upper extremity items of the Fugl-Meyer Assessment (FMA) were evaluated before and after the training period. Results: The total score gains of the FMA, FMA wrist item, and FMA finger item were significantly larger in the RFE under NMES group than those in the CT group (p < 0.05). Conclusion: The combination of voluntary movement and electrical stimulation may promote the activation of paralyzed muscles and improve distal function for very severe paralyzed upper limbs.

Factors necessary for independent walking in patients with thalamic hemorrhage.

BACKGROUND: Thalamic hemorrhages cause motor paralysis, sensory impairment, and cognitive dysfunctions, all of which may significantly affect walking independence. We examined the factors related to independent walking in patients with thalamic hemorrhage who were admitted to a rehabilitation hospital. METHODS: We evaluated 128 patients with thalamic hemorrhage (75 men and 53 women; age range, 40-93 years) who were admitted to our rehabilitation hospital. The mean duration from symptom onset to rehabilitation hospital admission was 27.2 ± 10.3 days, and the mean rehabilitation hospital stay was 71.0 ± 31.4 days. Patients' neurological and cognitive functions were examined with the National Institutes of Health Stroke Scale (NIHSS) and Mini-Mental State Examination (MMSE), respectively. The relationship between patients' scores on these scales and their walking ability at discharge from the rehabilitation hospital was analyzed. Additionally, a decision-tree analysis was used to create a model for predicting independent walking upon referral to the rehabilitation hospital. RESULTS: Among the patients, 65 could walk independently and 63 could not. The two patient groups were significantly different in terms of age, duration from symptom onset to rehabilitation hospital admission, hematoma type, hematoma volume, neurological symptoms, and cognitive function. The decision-tree analysis revealed that the patient's age, NIHSS score, MMSE score, hematoma volume, and presence of ventricular bleeding were factors that could predict independent walking. CONCLUSIONS: In patients with thalamic hemorrhage, the neurological symptoms, cognitive function, and neuroimaging factors at onset are useful for predicting independent walking.

Ability of electrical stimulation therapy to improve the effectiveness of robotic training for paretic upper limbs in patients with stroke.

We investigated whether untriggered neuromuscular electrical stimulation (NMES) can increase the effectiveness of shoulder and elbow robotic training in patients with hemiparesis. Thirty subacute stroke patients were randomly equally allocated to robot only (RO) and robot and electrical stimulation (RE) groups. During training, shoulder and elbow movements were trained by operating the robotic arm with the paretic arm, and the robotic device helped to move the arm. In the RE group, the anterior deltoid and triceps brachii muscles were electrically stimulated at sub-motor threshold intensity. Training was performed (approximately 1h/day, 5 days/week for 2 weeks) in addition to regular rehabilitation. Active range of motion (ROM) values of shoulder flexion and abduction, and Fugl-Meyer assessment (FMA) scores were measured before and after training. Active shoulder ROM was significantly better after than before training in the RE group; however, no such improvement was noted in the RO group. FMA scores were significantly better in both groups, and there was no significant difference between the groups. Untriggered NMES might increase the effectiveness of shoulder and elbow robotic training in patients with hemiparesis. Additionally, NMES at a sub-motor threshold during robotic training might facilitate activation of paretic muscles, resulting in paralysis improvement.

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.

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.

Inhibition of 1, 2-dimethylhydrazine-induced mucin-depleted foci and O6-methylguanine DNA adducts in the rat colorectum by boiled garlic powder.

The scavenging capacity of reactive oxygen species, such as hydroxyl radicals, is reported not to decrease in boiled garlic (an odorless garlic preparation). We therefore examined the modifying effect of boiled garlic powder (BGP) on 1,2-dimethylhydrazine-induced mucin-depleted foci (MDF) and aberrant crypt foci (ACF), preneoplastic lesions, in the rat colorectum. Male F344 rats (5 weeks old) were fed a basal diet, or experimental diets containing 5% or 1% BGP for 5 weeks. One week later, all rats were injected s.c. with DMH (40 mg/kg, once weekly for 2 weeks). At 10 weeks of age, all the rats were sacrificed, and the colorectum was evaluated for MDF and ACF. In rats given DMH and the 5% or 1% BGP diets (Groups 2 and 3), the numbers of MDF decreased significantly in a dose-dependent manner, compared with the DMH and basal diet value (Group 1) (p<0.01). The numbers of ACF in Group 2, but not Group 3, showed a non-significant tendency to decrease. Next, the effects of BGP on the formation of DMH-induced O6-methylguanine (O6-MeG) DNA adducts in rats were studied. Male F344 rats (5 weeks old) were fed the basal diet, or 10% BGP diet for 5 weeks. All rats were injected i.p. once with 40 mg/kg DMH at the end of week 5. The animals were sacrificed 6 hours after DMH injection to analyze the O6-MeG DNA adducts in the colorectal mucosa. Dietary administration of BGP significantly inhibited the O6-MeG DNA adduct levels in the colorectal mucosa, compared with the controls (p<0.01). These results suggested that BGP may exert chemopreventive effects against colon carcinogenesis at least in the initiation stage.

Inhibitory effects of high temperature- and pressure-treated garlic on formation of 1,2-dimethylhydrazine-induced mucin-depleted foci and O(6)-methylguanine DNA adducts in the rat colorectum.

High temperature- and pressure-treated garlic (HTPG) has been reported to have enhanced antioxidative and cytotoxic activities. However, there have been no reports on chemopreventive effects using animal cancer models. This study first examined the modifying effects of HTPG on 1,2-dimethylhydrazine (DMH)-induced mucin-depleted foci (MDF) and aberrant crypt foci (ACF), preneoplastic lesions in the rat colorectum. Male F344 rats (5 weeks old) were fed basal diet, or experimental diets containing 1% or 3% HTPG for 5 weeks. One week later, all rats were injected s.c.with DMH (40 mg/kg, once weekly for 2 weeks). At 10 weeks of age, all the rats were sacrificed, and the colorectum was evaluated for MDF and ACF. In rats given DMH and 3% HTPG, the numbers of MDF were decreased significantly as compared with those of rats given DMH alone (p< 0.01), and the numbers of ACF showed a tendency to decrease, although not significantly. Next, the effects of HTPG on the formation of DMH-induced O6-methylguanine (O6-MeG) DNA adducts in rats were studied. Male F344 rats (5 weeks old) were fed the basal diet or 10% HTPG diet for 5 weeks. All rats were injected i.p. once with 40 mg/kg DMH at the end of week 5. The animals were sacrificed 6 hours after DMH injection to analyze the O6-MeG DNA adducts in the colorectal mucosa and liver. Dietary administration of HTPG significantly reduced the adduct levels in the colorectal mucosa and liver, compared with the controls (both p< 0.01). The activities of some detoxification enzymes in the liver of DMH-treated rats were also measured. HTPG significantly reduced the activity of cytochrome P450 (CYP) 2E1, known to be responsible for activation of DMH in rat liver (p< 0.05). In contrast, HTPG significantly enhanced the activities of phase 2 enzymes, quinone reductase (QR) and glutathione S-transferase (GST), in rat liver (both p< 0.05). These results suggested that HTPG might have chemopreventive effects against colon carcinogenesis, at least in the initiation stage.

Antidiabetic effects of dietary administration of Aloe arborescens Miller components on multiple low-dose streptozotocin-induced diabetes in mice: investigation on hypoglycemic action and systemic absorption dynamics of aloe components.

We carried out three experimental trials to determine antidiabetic effects of Aloe arborescens Miller components. Firstly, ICR mice which received frequent injections of streptozotocin (Sz) in small doses (low-dose Sz-induced diabetes mice) were fed ad libitum with basal diets supplemented with components of Aloe arborescens Miller var. natalensis Berger (Kidachi aloe) and Aloe vera Linne from 31 days before to 73 days after the Sz injections. Variation in blood glucose levels, incidence rates of insulitis and blood insulin levels were examined during the trial. As a result, groups receiving diets supplemented at the rate of 2% with whole leaf of Kidachi aloe and 10 KDa fraction powder (a fraction with less than 10 KDa molecular weight derived from Kidachi aloe leaf skin juice by ultra filtration) significantly suppressed the elevation of blood sugar as compared to a control group receiving basal diet. In contrast, there was no significant effect with Aloe vera leaf pulp powder. Insulitis emerged at the rate of 87% in the basal diet group. On the contrary, the whole aloe leaf and 10 KDa fraction groups significantly decreased the incidence of insulitis and incidence rates of whole aloe leaf and 10 KDa fraction powder were 51 and 38%, respectively. While insulin levels in the basal diet group averaged at 0.05 ng, more than four times the insulin level was observed in the 10 KDa group relative to the basal diet group. Secondary, the inhibitory effects of test materials on intestinal glucose absorption were observed using the jejunum of rats. A strong inhibitory action on intestinal glucose absorption was observed in the 10 KDa fraction powder group. Thirdly, phenol compounds derived from aloe in the blood serum and organs were quantitatively measured by a HPLC following forced administration of aloe components to rats to determine absorption kinetics of aloe components inside the body. The primary component of aloe phenol compounds is the same component of the 10 KDa fraction powder and it was found in the pancreas and liver in addition to in the blood serum. The above results indicate that fore and aft when Sz injections could cause selective toxicity to B cells of islets, the dietary administration of 10 KDa fraction powder to mice would lead to the persistence of aloe phenol compound having an antioxidant activity in the pancreas and blood, which could protect islets of Langerhans from the destruction caused by methyl radical derived from Sz. The results also suggested the possibility of the 10 KDa fraction powder to alleviate the burden of insulin secretion as it has an inhibitory action on glucose absorption in the jejunum of rats.

Effects of aloe arborescens ingestion on azoxymethane-induced intestinal carcinogenesis and hematological and biochemical parameters of male F344 rats.

We examined the modifying effect of freeze-dried whole-leaf Aloe arborescens Miller var. natalensis Berger (Kidachi aloe in Japan; designated as 'ALOE') on azoxymethane (AOM)-induced intestinal carcinogenesis in rats. Male F344 rats (4 weeks old) were fed basal diet or experimental diet containing 0.2% or 1% ALOE for 28 weeks. Starting two weeks later, the animals received subcutaneous injections of AOM once weekly for 10 weeks. The incidence of colorectal adenocarcinomas in the 0.2% (but not 1%) ALOE group showed a strong tendency for decrease (p = 0.056) from the control group. Further, the adenocarcinoma incidence in the entire intestine (small and large intestines) in the 0.2% ALOE group was significantly (p = 0.024) decreased compared to the control value. However, there were no significant differences in tumor multiplicities of colorectal or entire intestines among the 3 groups. In addition, we also studied the safety of long-term ingestion of ALOE as a health food or natural thickening stabilizer. Rats were fed the basal diet or 1% ALOE diet for 35 weeks without AOM treatment. Feeding with 1% ALOE did not affect most hematological and serum biochemical parameters in the rats. These results indicate that a low level of ALOE ingestion might have a mild suppressive effect on intestinal tumor growth without harmful side effects.