Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

The Group Reminiscence Approach Can Increase Self-Awareness of Memory Deficits and Evoke a Life Review in People With Mild Cognitive Impairment: The Kurihara Project Data.

OBJECTIVES: The group reminiscence approach (GRA) and reality orientation (RO) are common psychosocial interventions for patients with dementia. As a qualitative evaluation of the reminiscence approach in patients with dementia, the Patient Report Outcome (PRO) is useful. The purpose of this study was to investigate the effects of GRA-RO for participants with mild cognitive impairment (MCI) using the PRO. DESIGN: A cluster randomized controlled trial. SETTING: Community-based study. PARTICIPANTS: Ninety-four patients with MCI (39 GRA-RO, 23 physical activity, and 32 cognitive training) described their impressions. INTERVENTION: Based on the database of the Kurihara Project, we retrospectively analyzed the participants' descriptions of their impressions as a PRO in the nonpharmacological interventions: GRA-RO, physical activity, and cognitive training. We categorized the descriptions according to the following 2 types: impression with content and reminiscence with life review. We assessed what they wrote regarding memory loss. The content on their life reviews was also a particular focus for the GRA-RO group. MEASUREMENTS: PRO. RESULTS: Compared with the physical activity and the clinical training groups, the GRA-RO patients described their reminiscence with life review and their own memory problems. There was no confusion of the order of events of their autobiographical memories. There was a significant time effect between the 2 family involvement groups in quality-of-life (QOL) scores, and the postintervention QOL scores were significantly better than preintervention. CONCLUSION: This study suggests that the GRA-RO in participants with MCI not only stimulates life review but also increases self-awareness of memory deficits without confusion of the order of events. Thus, the GRA-RO may improve self-esteem and develop self-awareness.

[Evaluation of Gastric Mucosal Injury Model Animals of Rebamipide Formulation--Study of Therapeutic Equivalence].

The introduction of generic drugs is promoted from the perspective of medical economics. In this context, we need to understand not only the bioequivalence of generic drugs specified in "the Guidelines for Bioequivalence Studies of Generic Products", but also formulation properties to consider their effect on pharmacological therapy. We evaluated the pharmaceutical characteristics of rebamipide formulations, a brand-name drug and two generic drugs, and their clinical functionality by using rat models of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Pharmaceutical evaluation showed significant differences in hardness. The inter-lot variation was small in all rebamipide formulations. In the clinical functionality study, biochemistry test values 7 d after the administration of rebamipide showed no differences among formulations. Higher levels of mucosal fluid secretion and antioxidative enzymes were observed in the groups administered rebamipide than in the control group. The levels of lipid peroxide were lower in the groups administered rebamipide than the control group. Multivariate analysis showed slight divergence between the brand-name and generic drugs. In future, it will be necessary to select generic drugs after careful consideration of bioequivalence, clinical functionality, and therapeutic equivalence by reviewing scientific evidence such as indication and formulation design, not to mention stable provision.

Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8.

Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

Novel neurotrophic phenylbutenoids from Indonesian ginger Bangle, Zingiber purpureum.

Two new curcuminoids 1 and 2, and a new phenylbutenoid dimer 3, were isolated from Bangle (Zingiber purpureum). Their structures were determined on the basis of comprehensive spectroscopic data and their biogenetic pathway. Compounds 1 and 2 are the first example of curcumin coupled with phenylbutenoid. Compounds 1 and 2 promoted neurite outgrowth of NGF-mediated PC12 cells at concentrations ranging from 1 to 10 µM. In addition, compound 1 was found to accelerate the prevention of Aß42 aggregation.

Outcome evaluation of an intervention to improve the effective and safe use of meropenem.

BACKGROUND: Pharmacists have been involved in promoting the proper and safe use of antimicrobial drugs in our institution since 2010. Setting Kochi Medical School Hospital, Japan. OBJECTIVE: To design and evaluate a plan of administration of meropenem (MEPM) based on its pharmacokinetics and pharmacodynamics, drug sensitivity, bacterial cultures, patient condition and renal function. METHOD: A total of 547 patients admitted between April 2010 and March 2013 with serious infections who were successfully treated with MEPM for three or more days were analysed. Patients were initially divided into two groups according to renal function: group A consisted of patients with mild renal dysfunction [creatinine clearance (CLcr) > 50 mL/min] while group B consisted of patients with moderate to severe renal dysfunction (CLcr ≤ 50 mL/min). These groups were then subdivided into two groups according to the implementation of pharmacist intervention. MAIN OUTCOME MEASURES: Daily dose, frequency of administration, dose interval, duration of therapy, adverse events and cost reduction. RESULTS: In the non-intervention subgroup within group A, the daily dose was 1,000 mg/day, the frequency of administration was 1.8 ± 0.6 times/day, and the duration of therapy was 9.4 ± 5.4 days. In the intervention subgroup within group A, the daily dose was 1,500 mg/day, the administration frequency was 2.5 ± 0.6 times/day, and the duration of therapy was 7.4 ± 3.7 days. Although the dose was higher (P < 0.05) and the duration of therapy was an average of 2 days shorter (P < 0.05) in the intervention subgroup, there was no significant difference in the rate of adverse events between the two subgroups. In group B, there were no significant differences between the two subgroups in the daily dose, administration frequency, or duration of therapy. However, liver dysfunction was significantly more common in the non-intervention subgroup than in the intervention subgroup (P < 0.05). The total reduction in drug cost in the intervention groups was estimated to be US$17,490 over 3 years. CONCLUSION: Pharmacist intervention was associated with a shorter duration of therapy, lower drug costs, and decreased adverse effect. We believe that our intervention is beneficial in terms of effectiveness and safety, and supports proper antimicrobial use.

Apathy is more severe in vascular than amnestic mild cognitive impairment in a community: the Kurihara Project.

AIM: The aim of this study was to estimate the prevalence of apathy, and to compare vascular mild cognitive impairment (vMCI), amnestic MCI (amMCI), and other type using Clinical Assessment for Spontaneity (CAS). METHODS: Agreement to take part in the study was obtained from 590 community dwellers, aged ≥75 years living in Kurihara, Japan. Of the 590 subjects, 221 had a clinical dementia rating (CDR) of 0 (normal); 295 had CDR 0.5 (mild cognitive impairment; MCI); and 74 had CDR 1+ (dementia). The CDR 0.5 subjects were divided into three groups: 55 with vMCI (Erkinjuntti et al. criteria), 91 with amMCI and 149 with other type. To evaluate the various aspects of apathy, we used the three CAS subscales: clinical interview (CAS1), self-evaluation (CAS2), and caregiver assessment (CAS3). Three analyses were then performed to determine: (i) the validity of CAS; (ii) the prevalence rate of apathy in CDR 0 versus CDR 0.5 versus CDR 1+; and (iii) the prevalence rate of apathy in normal versus vMCI versus amMCI versus other type. RESULTS: CAS was validated with the Apathy Evaluation Scale. There were significant differences among the three CDR groups in CAS1, CAS2 and CAS3 (P < 0.001). The prevalence rate of apathy in each CAS in the CDR 1+ group was higher than the CDR 0.5 group, which was higher than the CDR 0 group. There was a significant difference in CAS3 score between the four groups (the normal and the three subgroups; P < 0.001). Apathy in vMCI was more severe than in the other three groups (P < 0.05) on CAS3 score. CONCLUSIONS: vMCI subjects have more severe apathy compared with amMCI subjects on caregiver assessment.

Phenylbutenoid dimers isolated from Zingiber purpureum exert neurotrophic effects on cultured neurons and enhance hippocampal neurogenesis in olfactory bulbectomized mice.

Trans-3-(3'4'-dimethoxyphenyl)-4-[(E)-3",4"-dimethoxystyryl]cyclohex-1-ene (Comp.1) and cis-3-(3'4'-dimethoxyphenyl)-4-[(E)-3",4"-dimethoxystyryl]cyclohex-1-ene (Comp.2), phenylbutenoid dimers, have been isolated as neurotrophic molecules from an Indonesian medicinal plant, Zingiber purpureum. The aim of this study was to explore the neurotrophic effects of Comp.1 and Comp.2 in vitro and in vivo. Comp.1 (10-30 µM) or Comp.2 (30 µM) significantly induced neurite sprouting in PC12 cells. Comp.1 (0.03-3 µM) or Comp.2 (0.3-3 µM) significantly increased the neurite length and number of neurites in primary cultured rat cortical neurons. Comp.1 (30 µM) and Comp.2 (3-30 µM) also provided significant protection against cell death caused by deprivation of serum. The in vivo effects of both Comp.1 and Comp.2 were evaluated on hippocampal neurogenesis in olfactory bulbectomized (OBX) mice, an experimental depression and dementia animal model. Comp.1 (50mg/kg p.o.), Comp.2 (50mg/kg p.o.), or fluoxetine (10mg/kg i.p.), an antidepressant, were administrated once a day on days 15-28 after OBX. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Immunohistochemical analysis showed that the number of BrdU/NeuN double-labeled cells in the dentate gyrus was significantly decreased 30 days after OBX. Chronic treatment with Comp.1, Comp.2 or fluoxetine significantly increased the number of BrdU/NeuN double-labeled cells. These results indicate that Comp.1 and Comp.2 have neurotrophic effects, and have the potential for disease modification in depression and dementia.

Syntheses of structurally-simplified and fluorescently-labeled neovibsanin derivatives and analysis of their neurite outgrowth activity in PC12 cells.

The syntheses of several neovibsanin derivatives were carried out in order to elucidate the simple structure required for displaying neurite outgrowth activity. In addition, a fluorescent probe molecule was synthesized and the analysis of its behavior in the PC12 cell line showed that the neovibsanins accumulate on the outer edge of the cell at the site of formation of prominences.

Invasion inhibitors of human fibrosarcoma HT 1080 cells from the rhizomes of Zingiber cassumunar: structures of phenylbutanoids, cassumunols.

The methanolic extract and its EtOAc-soluble fraction from the rhizomes of Zingiber cassumunar inhibited invasion of human fibrosarcoma HT 1080 cells. From the EtOAc-soluble fraction, eight new phenylbutanoids, cassumunols A-H, were isolated together with 30 known constituents. The structures of new phenylbutanoids were elucidated on the basis of chemical and physicochemical evidence. Principal constituents were examined the inhibitory effects on the invasion of HT 1080 cells. Among them, phlain I and III, (E)-1-(3,4-dimethoxyphenyl)buta-1,3-diene, (E)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene, and (-)-ß-sesquiphellandrene showed anti-invasion effects. Interestingly, (E)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene [inhibition (%) 46.8 ± 7.2 (p<0.05) at 30 µM] significantly inhibited the invasion, and only a weak cytotoxic effect was observed.