Visual imagery imitation skills and cognitive functions in patients with Schizophrenia.

Background/Objectives: Visual demonstration by occupational therapists is very common in psychiatric treatment, however, some patients with schizophrenia could not imitate the actions despite the absence of any physical impairments. Therefore, the purpose of this study was to identify how cognitive functions such as attention and cognitive processes in the imitation process is necessary and how these processes were related to the ability to convert this into action (imitation) in patients with schizophrenia. Method: The participants were patients with schizophrenia with mean age 59.2 (± 11.3) years, 23 were men and 10 were women. The participants were tested for imitation ability and cognitive function, working memory, and motor imagery. Results: Three subjects achieved full scores in the visual imitation test. However, the median of the total score was 10.0, with many subjects failing to imitate multiple tasks. Imitation learning is associated with duration of illness(t = -4.09, p = .000), mental health(t = -2.30, p = .029), and cognitive function such as the ability to retain visual information(t = -2.97, p = .006), and that these factors are interrelated. Conclusion: To effectively promote imitation learning in patients with schizophrenia, occupational therapists need to establish teaching methods that make it easier for learners to retain visual information from the early stages of their illness.

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina.

Calcium antagonists are used for coronary spastic angina (CSA) treatment. We previously identified a phospholipase C (PLC) -δ1 gene variant that results in enhanced PLC activity in patients with CSA and developed a CSA animal model by generating vascular smooth muscle cell-specific human variant PLC-δ1 overexpression (PLC-TG) mice. In this study, we investigated the molecular mechanism of CSA using the PLC-TG mice and the inhibitory effect of a calcium antagonist, diltiazem hydrochloride (DL).We treated the PLC-TG and wild-type (WT) mice with oral DL or trichlormethiazide (TM) (control) for 2 weeks. Ergometrine injection-induced coronary spasm was observed on the electrocardiogram in all 5 PLC-TG mice treated with TM, but only in 1 of 5 PLC-TG mice treated with DL. Voltage-dependent calcium channel (Cav1.2) phosphorylation and protein kinase C (PKC) activity were enhanced in the aortas of PLC-TG mice treated with TM. DL treatment significantly inhibited Cav1.2 phosphorylation and PKC activity. Although total Cav1.2 expression was similar between WT and PLC-TG mice treated with TM, DL treatment significantly increased its expression in PLC-TG mice. Furthermore, its expression remained high after DL discontinuation. DL and PKC inhibitor suppressed intracellular calcium response to acetylcholine in cultured rat aortic smooth muscle cells transfected with variant PLC-δ1.These results indicate that enhanced PLC activity causes coronary spasm, presumably via enhanced Cav1.2 phosphorylation and PKC activity, both of which were inhibited by DL. Enhanced total Cav1.2 expression after DL discontinuation and high PKC activity may be an important mechanism underlying the calcium antagonist withdrawal syndrome.

Japan's Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis.

Zinc deficiency is common in Japan, yet awareness on this disorder is lacking. The Japanese Society of Clinical Nutrition recently issued the Japan's Practical Guideline for Zinc Deficiency 2018 setting forth criteria for diagnosing zinc deficiency, i.e., (a) one or more symptoms of zinc deficiency or low serum alkaline phosphatase, (b) ruling out other diseases, (c) low serum zinc, and (d) alleviation of symptoms upon zinc administration. Serum zinc <60 µg/dL and 60-80 µg/dL indicate zinc deficiency and marginal deficiency, respectively. Zinc deficiency symptoms vary and include dermatitis and taste disorders among others. Zinc administration improves taste in 50-82% of patients suffering from taste disorders (a common symptom of zinc deficiency). Effects of zinc administration do not appear immediately, and therapy should be continued for at least three months. Zinc deficiency often accompanies various diseases and conditions. Here, we focus on inflammatory bowel diseases and liver cirrhosis. As zinc deficiency enhances intestinal inflammation via macrophage activation, we discuss the pathological mechanism for inflammation and zinc deficiency in the context of IBD. Zinc deficiency can also lead to a nitrogen metabolic disorder in patients with liver cirrhosis. Zinc supplementation can improve not only the ammonia metabolism, but also the protein metabolism. We also discuss directions for future studies of zinc deficiency.

Ginsenoside Rb1 promotes intestinal epithelial wound healing through extracellular signal-regulated kinase and Rho signaling.

BACKGROUND AND AIM: Daikenchuto, a traditional Japanese herbal medicine, has been reported to exhibit anti-inflammatory effects against intestinal inflammation. However, whether daikenchuto has a therapeutic effect against intestinal mucosal injuries remains unclear. Thus, the aim of this study was to determine the effect of daikenchuto on intestinal mucosal healing. METHODS: Colitis was induced in male Wistar rats by using trinitrobenzenesulfonic acid. Daikenchuto (900 mg/kg/day) was administered for 7 days after the induction of colitis. Thereafter, intestinal mucosal injuries were evaluated by determining the colonic epithelial regeneration ratio ([area of epithelial regeneration/area of ulcer] × 100). Restoration of rat intestinal epithelial cells treated with daikenchuto and its constituent herbs (Zanthoxylum fruit, processed ginger, and ginseng) and ginsenoside Rb1, which is a ginseng ingredient, was evaluated using a wound-healing assay. RESULTS: The colon epithelial regeneration ratio in the daikenchuto-treated rats was significantly higher than that in the control rats. Daikenchuto, ginseng, and ginsenoside Rb1 enhanced wound healing, and the ginsenoside Rb1-induced enhancement was inhibited by extracellular signal-regulated kinase and Rho inhibitors. CONCLUSIONS: Daikenchuto and its constituent, ginsenoside Rb1, promoted wound healing. Because mucosal healing is one of the most important therapeutic targets in patients with inflammatory bowel disease, ginsenoside Rb1 may be a novel therapeutic agent against intestinal mucosal damage such as that occurring in intestinal bowel disease.

Inhibition of catechol-O-methyltransferase in the cynomolgus monkey by opicapone after acute and repeated administration.

INTRODUCTION: The aim of the study was to clarify the dose response for inhibition of catechol-O-methyltransferase (COMT) by opicapone, a third generation COMT inhibitor, after acute and repeated administration to the cynomolgus monkey with pharmacokinetic evaluation at the higher dose. METHODS: Three cynomolgus monkeys were used in the study. In the first experiment, COMT inhibition was evaluated over 24 h after the first and at 24 h after the last of 14 daily oral administrations of vehicle, 1, 10 and 100 mg/kg opicapone using a crossover design. In the second experiment, the effect of the maximally effective dose, 100 mg/kg, was retested under the same conditions with additional monitoring of plasma opicapone levels to explore the relationship between pharmacokinetics and pharmacodynamics. RESULTS: Opicapone dose-dependently inhibited COMT activity, significantly so at 10 and 100 mg/kg. Maximal inhibition was 13.1%, 76.4% and 93.2% at 1, 10 and 100 mg/kg respectively, and COMT remained significantly inhibited at 24 h after 10 and 100 mg/kg (42.6% and 60.2% respectively). Following repeated administration of opicapone residual COMT inhibition at 24 h was 15-25% greater at all doses. In contrast to its pharmacodynamic effect, opicapone was rapidly absorbed and eliminated, with no accumulation in plasma following repeated administration. CONCLUSION: Opicapone showed sustained and dose-dependent COMT inhibition despite being rapidly eliminated from plasma and with no evidence for accumulation in plasma after 14 days administration. Opicapone fills the unmet need for a compound with sustained COMT inhibition which will improve levodopa bioavailability in patients with Parkinson's disease.

Role of Cranial Temperature in Neuroprotection by Sodium Hydrogen Sulfide After Cardiac Arrest in Mice.

The hydrogen sulfide donor sodium hydrogen sulfide (NaHS) is recognized as a neuroprotective agent, which induces a hibernation-like metabolic state and hypothermia. However, it remains unclear whether it is the sulfide itself or the hypothermia induced by the sulfide that mediates treatment outcomes following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). We therefore tested whether NaHS improved outcomes following CA/CPR in mice maintained at 35.0°C by active warming during recovery. Adult male mice were subjected to 8 minutes CA/CPR and randomly treated intraperitoneally with either implantation of miniosmotic pump with NaHS (50 µmol/kg/day) for 3 days or vehicle 30 minutes after CPR. A normothermia group had cranial temperatures kept >35.0°C for 6 hours with a heat pad, and a hypothermia group was allowed to spontaneous hypothermia at room temperature (26.0°C). Behavioral testing and histological evaluation of neurons in the CA1 hippocampal region and striatum were performed on days 4 and 12 after CA/CPR. Both cranial and body temperature decreased following CA/CPR in the hypothermia group, and this was enhanced by NaHS treatment. In the active warming (normothermia) group, NaHS protected striatal neurons and improved long-term survival, which was comparable to the hypothermia groups. No differences were found in the CA1 region. Following CA/CPR, NaHS treatment decreased the heart rate, but not the mean arterial pressure. Our study demonstrated that post-CPR treatment with NaHS exerted neuroprotection in mice while maintaining a normal cranial temperature, indicating that NaHS-related neuroprotection is independent of the known protective effect of spontaneous hypothermia.

Lactobacillus brevis KB290 With Vitamin A Ameliorates Murine Intestinal Inflammation Associated With the Increase of CD11c+ Macrophage/CD103- Dendritic Cell Ratio.

Background: The ratio of colonic anti-inflammatory CD11c+ macrophages (MPs) to inflammatory CD103- dendritic cells (DCs) plays pivotal roles in intestinal inflammation. Little is known about how the ratio is regulated by lactic acid bacteria (LAB) and bifidobacteria (Bif). We investigated the contribution of LAB/Bif to this ratio. Methods: We established an in vitro experimental system using human myeloblastic KG-1 cells, which differentiate into CD11c+ MP-like (CD11c+ MPL) and CD103- DC-like (CD103- DCL) cells, and explored effective LAB/Bif strains. The selected strain's effect on the colonic CD11c+ MP/CD103- DC ratio and intestinal inflammation was examined in mice, and the strain's underlying mechanisms were investigated in vitro. Results: We screened 19 strains of LAB/Bif, and found that Lactobacillus brevis KB290 (KB290) increased the CD11c+ MPL/CD103- DCL cell ratio only in the presence of a vitamin A (VA) metabolite, retinoic acid (RA). Supplementation of KB290 with VA increased the CD11c+ MP/CD103- DC ratio in healthy mouse and prevented the disruption of the ratio during colitis. Supplementation of KB290 with pro-VA (ß-carotene) also increased the ratio in healthy mouse and ameliorated the development of colitis. The ratio was increased by reduction of CD103- DCs (or CD103- DCL cells). Our in vitro data suggested that KB290 induced cell death in CD103- DCL cells in the presence of RA signaling. Conclusions: Supplementation of KB290 with VA increases the colonic CD11c+ MP/CD103- DC ratio associated with the amelioration of murine colitis, suggesting a possible way to control intestinal inflammation by LAB.

Effects of suppressed bone remodeling by minodronic acid and alendronate on bone mass, microdamage accumulation, collagen crosslinks and bone mechanical properties in the lumbar vertebra of ovariectomized cynomolgus monkeys.

Collagen crosslinking is an important determinant of the quality of bone material. We have previously shown that suppressed bone turnover by high doses of minodronic acid and alendronate increases compressive strength of vertebra, but also increases microdamage accumulation, in monkey bone. The aim of this study is to examine the effects of these bisphosphonates on collagen crosslinks and intrinsic material properties, in addition to microdamage accumulation, in vertebral cancellous bone in ovariectomized cynomolgus monkeys. Sixty female monkeys aged 9-17years were divided into five groups: sham and ovariectomized groups were treated daily for 17months with lactose vehicle, and the other three groups were given minodronic acid daily at 0.015 or 0.15mg/kg or alendronate daily at 0.5mg/kg orally. After sacrifice, lumbar vertebrae were subjected to histomorphometry, microdamage measurement, analysis of collagen crosslinking and compressive mechanical tests. Minodronic acid caused dose-dependent suppression of increased bone remodeling due to ovariectomy, and low-dose minodronic acid suppressed remodeling same level as alendronate. However, low-dose minodronic acid did not change microdamage accumulation, collagen maturity and the pentosidine level, whereas high-dose minodronic acid and alendronate increased these parameters. Compressive ultimate load was increased following high-dose minodronic acid and alendronate, but no treatment altered the reduction in intrinsic material properties caused by ovariectomy. These findings suggest that deterioration of bone material and formation of pentosidine and microdamage induced by minodronic acid is less than that expected based on the extent of remodeling suppression, in comparison with alendronate, but this was not reflected in any significant change of mechanical properties.

Difficulties in Performing Mesalazine Enemas and Factors Related to Discontinuation Among Patients With Ulcerative Colitis.

Current first-line treatment of ulcerative colitis consists of a combination of mesalazine enemas and oral mesalazine; however, many patients may discontinue mesalazine enemas. In this single-center, cross-sectional study, 165 outpatients with ulcerative colitis completed a self-administered questionnaire regarding the frequency of mesalazine enemas, difficulties in performing these enemas, and factors possibly associated with their discontinuation, as well as patient clinical and demographic characteristics. Of 165 patients, 34 (20.6%) discontinued mesalazine enemas because of a lack of efficacy. Five of the 13 items assessing difficulties were answered affirmatively by the majority of patients. Discontinuation of enema application was associated with a perceived lack of efficacy, four or more bowel movements per day, and lower scores on measurement of the doctor-patient relationship. Application of mesalazine enemas by patients with ulcerative colitis may be improved by discussions with peers and healthcare professionals and by adjusting the frequency of application or the time of starting the enema based on worsening of ulcerative colitis.

Evaluation of crystallographic orientation of biological apatite in vertebral cortical bone in ovariectomized cynomolgus monkeys treated with minodronic acid and alendronate.

Quantitative analysis of the orientational distribution of biological apatite (BAp) crystals is proposed as a new index of bone quality. This study aimed to analyze BAp c-axis orientation in ovariectomized (OVX) monkeys treated with amino-bisphosphonates minodronic acid and alendronate as reference. Sixty female monkeys aged 9-17 years were divided into five groups: one sham group and four OVX groups. The sham group and one OVX group were treated daily with vehicle for 17 months. The other three groups were treated daily with minodronic acid at doses of 0.015 and 0.15 mg/kg, and alendronate at 0.5 mg/kg orally, respectively. The seventh lumbar vertebrae were subjected to analysis of the preferential BAp c-axis orientation in the ventral cortical bone. The BAp c-axis orientation along the craniocaudal axis was significantly increased in the OVX monkeys. The high dose of minodronic acid suppressed the OVX-induced increase in the BAp c-axis orientation, whereas alendronate showed a non-significant tendency to suppress the increase in the orientation. In analysis with other parameters, the BAp c-axis orientation was positively correlated with bone formation indices in biochemical markers and bone histomorphometry and negatively correlated with the increase in lumbar bone mineral density. On the other hand, the BAp c-axis orientation was not correlated with bone resorption indices, except for the eroded surface. These results indicate that the increase in BAp c-axis orientation was ameliorated by minodronic acid treatment in OVX monkeys, mainly by suppression of bone formation increase.

[A New Teaching Model for Practicing Ultrasound-guided Regional Anesthesia Techniques].

We developed a simulator using "slime" composed of polyvinyl alcohol (PVA) and borax to evaluate this new ultrasound-guided nerve block training model. Seventeen subjects used the training model in the present study. They had no previous experience in performing ultrasound-guided nerve block. A plastic case measuring 25 x 18 x 12 cm was filled with 8 cm of slime. Three pieces of gauze were placed between the slime layers at 2 cm intervals. An in-plane approach was used to visualize the needle for the nerve block, and the amount of time required to stop the needle on the second gauze was measured 5 times for each subject. Significant differences were observed between the times for the first experiment and those for the third experiment to the fifth experiment In the fourth and fifth experiments, all subjects visualized the nerve block needle clearly above the target layer and were able to stop the needle at the target layer. The present simulation using our proposed ultrasound-guided nerve block training model was useful in terms of the amount of time required to perform the procedure and as well as in terms of its safety.

Volume manipulation by phlebotomy for cesarean section in a patient with pulmonary hypertension.

Pulmonary hypertension in a parturient is known for its high perioperative mortality. We describe a successful case of cesarean section performed under general anesthesia in a parturient with pulmonary hypertension. A distinctive feature of our management was active blood volume manipulation by phlebotomy and reinfusion of the blood. Just after the baby was delivered, about 250 ml of blood was phlebotomized to counteract autotransfusion by the contracting uterus. We stopped phlebotomy at this volume because moderate systemic hypotension occurred. The blood was slowly infused, with transesophageal echocardiography used to evaluate right ventricle filling. The patient was hemodynamically stable during the operation and had an uneventful postpartum period. Her baby's perioperative course was also uneventful.

Moderate dietary temperance effectively prevents relapse of Crohn disease: a prospective study of patients in remission.

The authors examined the influence of diet (dietary fat intake and dietary temperance) on relapse of patients with Crohn disease. A 1-year prospective study of 76 patients with Crohn disease was conducted. The criterion for eligibility was a Crohn Disease Activity Index score of 150 or lower for at least 1 month. The primary end point was defined as the relapse-free interval from the baseline until the first relapse. Fat intake was assessed using a validated diet history questionnaire. The degree of dietary temperance was assessed using a single-item nominal scale. The Cox proportional hazards model was used to evaluate the influence of diet. Crohn disease relapse was seen in 25 patients (33%), and 47 patients (62%) remained in continuous remission. A decreased ratio of n-6 polyunsaturated fatty acid (PUFA) to n-3PUFA (odds ratio = .38; p = .005) was associated with a poor prognosis. Dietary temperance also was significantly associated with prognosis (p = .014). More moderate dietary temperance decreased the risk of relapse (odds ratio = .22; p = .006). Effective prevention of relapse for Crohn disease patients might be achieved through moderate dietary temperance, particularly when the disease condition is unstable.

Lignan and neolignan derivatives from Magnolia denudata.

A new tricyclo[4.2.0.0(2,8)]octane-type neolignan, 6-allyl-7-(3,4-dimethoxyphenyl)- 2,3-dimethoxy-8-methyl-tricyclo[4.2.0.0(2,8)]oct-3-en-5-one, together with 15 known lignan and neolignan derivatives have been isolated from the flower buds of Magnolia denudata DESR. and the structures of these compounds have been elucidated based on the 1H- and 13C-NMR spectra and two-dimensional NMR methods such as HMBC, HMQC, and NOESY.

Anti-atherosclerotic effect of soybean isofalvones and soyasaponins in diabetic rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the influence of soybean phytochemical extract containing isoflavones and soyasaponins (SPE) on blood glucose, blood lipids, plasma lipid peroxide and platelet aggregation activity in diabetic rats.</p><p><b>METHODS</b>Diabetic rats were fed with fodder containing 20 g/kg of SPE for 20 weeks. Their plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were separated by sequential ultracentrifugation.</p><p><b>RESULTS</b>Twenty weeks after experiment, level of blood glucose, atherosclerotic index and plasma level of lipid peroxide were (11.9 +/- 0.9) mmol/L, 0.40 +/- 0.14 and (15.7 +/- 0.5) mmol/L, respectively in diabetic rats fed with SPE, significantly lower than those in control rats not fed with it, (14.2 +/- 2.0) mmol/L, 0.58 +/- 0.22 and (20.7 +/- 3.0) mmol/L, respectively. Accordingly, platelet aggregation rates induced by ADP and collagen in the two groups were (54.1 +/- 8.8)% vs (66.6 +/- 12.4)% and (58.0 +/- 7.9)% vs (69.6 +/- 9.4)%, respectively. Changes in all these indices were significantly different between the two groups.</p><p><b>CONCLUSION</b>SPE could significantly decrease blood glucose, improve atherosclerotic index, and inhibit lipid peroxidation and platelet aggregation in diabetic rats, which might be useful in prevention and control of diabetes mellitus and diabetes-associated atherosclerosis.</p>

Physicochemical compatibility of propofol-lidocaine mixture.

UNLABELLED: To examine the physicochemical stability of combinations of propofol-lidocaine mixtures frequently used in clinical practice, we added lidocaine 5, 10, 20, or 40 mg to commercially available 1% propofol 20 mL. To assess chemical stability, propofol concentrations were determined by gas chromatography assay for 24 h after preparation of the mixture. In addition, scanning electron microscopy was used to determine the maximum detectable droplet size in randomly selected fields. Macroscopically, separate, colorless layers were first seen at 3 and 24 h after the addition of 40 and 20 mg of lidocaine to propofol, respectively, whereas the mixture with 5 or 10 mg of lidocaine was macroscopically stable. Propofol concentrations in the mixture with 40 mg of lidocaine decreased linearly and significantly from 4 to 24 h after preparation, whereas those combined with other lidocaine doses were unchanged compared with baseline concentrations. Scanning electron microscopy showed that droplets with diameters >or=5 microm first appeared 30 min after the addition of 40 mg of lidocaine to propofol, and the emulsion droplets were enlarged in a time- and dose-dependent fashion. Our results indicate that the addition of lidocaine to propofol results in a coalescence of oil droplets, which finally proceeds to a visible separate layer. Depending on the dose of lidocaine and the duration between its preparation and administration, this combination may pose the risk of pulmonary embolism. IMPLICATIONS: The addition of lidocaine to propofol results in time- and dose-dependent increases in oil droplet diameters in emulsion. This mixture is physicochemically unstable over time and may cause pulmonary embolism, depending on the dose of lidocaine.

[Postoperative analgesia with morphine with or without diclofenac after shoulder surgery].

Balanced analgesia using a narcotic and a nonsteroidal anti-inflammatory drug has been successfully tested for postoperative analgesia. This study was designed to examine the efficacy of such combination therapy after shoulder surgeries. Twenty ASA physical status I or II patients, scheduled for shoulder surgeries under general anesthesia, were randomly assigned to either morphine (M) group (n = 10), who received IV morphine patient-controlled analgesia (PCA) alone (2 mg as a bolus, lock-out interval of 10-minutes, and 10 mg as 1-hour limit for 48 hours), or morphine + diclofenac (M + D) group (n = 10), who received, in addition to morphine PCA, diclofenac suppositories 50 mg.8 h-1 starting immediately before surgical incision for 48 hours. Postoperative analgesic profiles, such as visual analog scale (VAS) at rest and on movement, and cumulative morphine consumption, the incidence and extent of side effects (nausea, vomiting, and time till the first bowel movement), and other complications were recorded. The two groups were similar demographically. Patients in the M + D group required 15.1 +/- 9.0 mg of morphine within 48 hours after surgery, while those in the M group required 30.5 +/- 21.0 mg of morphine (P < 0.05). No significant differences in VAS at rest and on movement were observed between the two groups. The time till the first bowel movement was significantly shorter in the M + D group. Our data suggest that diclofenac suppositories 50 mg.8 h-1 starting immediately before surgery for 48 h are effective adjuvant in reducing post-shoulder surgery morphine requirement and retardation of bowel movement.