Influences of Vitamin B12 Supplementation on Cognition and Homocysteine in Patients with Vitamin B12 Deficiency and Cognitive Impairment.

Vitamin B12 deficiency is associated with cognitive impairment, hyperhomocysteinemia, and hippocampal atrophy. However, the recovery of cognition with vitamin B12 supplementation remains controversial. Of the 1716 patients who visited our outpatient clinic for dementia, 83 had vitamin B12 deficiency. Among these, 39 patients (mean age, 80.1 ± 8.2 years) had undergone Mini-Mental State Examination (MMSE) and laboratory tests for vitamin B12, homocysteine (Hcy), and folic acid levels. The hippocampal volume was estimated using the z-score of the MRI-voxel-based specific regional analysis system for Alzheimer's disease. This is multi-center, open-label, single-arm study. All the 39 patients were administered vitamin B12 and underwent reassessment to measure the retested for MMSE and Hcy after 21−133 days (median = 56 days, interquartile range (IQR) = 43−79 days). After vitamin B12 supplementation, the mean MMSE score improved significantly from 20.5 ± 6.4 to 22.9 ± 5.5 (p < 0.001). Hcy level decreased significantly from 22.9 ± 16.9 nmol/mL to 11.5 ± 3.9 nmol/mL (p < 0.001). Significant correlation was detected between the extent of change in MMSE scores and baseline Hcy values. The degree of MMSE score was not correlated with hippocampal atrophy assessed by the z-score. While several other factors should be considered, vitamin B12 supplementation resulted in improved cognitive function, at least in the short term, in patients with vitamin B12 deficiency.

Effectiveness of a self-reporting yes/no survey for dementia screening-trial in Fukui, Japan.

Background: Early intervention for dementia patients is extremely important for the prevention of dementia. However, so far, it is not clear as to what kind of screening will be useful for the early detection of dementia. Objective: We aimed to investigate the relationship between the results of a short self-reporting yes/no survey selected in Kihon Checklist, developed by the Japanese Ministry of Health, Labor and Welfare to identify older adults who are at risk of requiring support/care, and other original items developed by Dementia Prevention Team, Fukui, Japan, and Mini-Mental State Examination (MMSE) scores, and determine the diagnostic efficacy of the self-reporting yes/no survey. Methods: Self-reporting yes/no surveys were conducted for 87,687 individuals aged ≥65 years, living in Fukui, Japan, and did not have Long-Term Care Insurance, Japan. According to the survey results, selected individuals were advised to visit a local hospital to be assessed with MMSE. Results: Individuals who could not make a call by looking up phone numbers and manage their own deposits and savings at the bank or automatic teller machine (ATM) had an increased risk of low MMSE score (≤23; odds ratio: 2.74 [1.89-3.97]; 95% confidence interval: 2.12 [1.46-3.07]). Conclusions: Self-reporting yes/no survey could effectively screen for dementia. Not being able to make a call by looking up phone numbers and not being able to manage their own deposits and savings at the bank or ATM are signs of dementia.

Influences of Folate Supplementation on Homocysteine and Cognition in Patients with Folate Deficiency and Cognitive Impairment.

Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.

Kidney Disease Associated With Anorexia Nervosa: A Case Series With Kidney Biopsies.

RATIONALE & OBJECTIVE: Anorexia nervosa is often intractable and induces various physical disorders, including kidney disease and mineral disorders, occasionally progressing to kidney failure. No consensus-based clinical practice guidelines have been established for patients with anorexia nervosa referred to a nephrologist. STUDY DESIGN: Patients with anorexia nervosa-associated kidney disease diagnosed were analyzed retrospectively. Kidney outcomes were defined as doubling of serum creatinine level and/or progression to end-stage kidney disease. SETTING & PARTICIPANTS: Patients with a history of anorexia nervosa with kidney disease, including electrolyte abnormalities, who were referred to our hospital between 1992 and 2017 were included. RESULTS: 14 female patients were included. The time from anorexia nervosa onset to the initial visit with a nephrologist was 17.8 years. At the first visit, median body mass index was 13.4 kg/m2, median serum creatinine level was 1.9 mg/dL, and median serum potassium level was 2.7 mmol/L. All patients showed hypokalemia and addictive vomiting or diuretic/laxative abuse. During the median observation period of 3.1 years, kidney outcomes occurred in 9 patients, and 2 died due to their anorexia nervosa. 4 patients underwent kidney biopsy. The kidney biopsy findings of these patients included hypertrophy of the juxtaglomerular apparatus, advanced glomerular collapse, and interstitial fibrosis, consistent with ischemic kidney injury and hypokalemic nephropathy. LIMITATIONS: The sample size was small, and kidney function was assessed based on serum creatinine levels in patients with anorexia nervosa with low muscle mass. CONCLUSIONS: Most patients with anorexia nervosa referred to nephrologists had kidney disease at the time of the first visit. Improving kidney outcomes of patients with anorexia nervosa may require earlier collaboration between psychiatrists and nephrologists.

Enzymatically modified isoquercitrin supplementation intensifies plantaris muscle fiber hypertrophy in functionally overloaded mice.

BACKGROUND: Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. METHODS: In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. RESULTS: In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. CONCLUSION: EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.

Piceatannol exhibits anti-inflammatory effects on macrophages interacting with adipocytes.

Piceatannol (PIC), a natural analog of resveratrol (RES), is a phytochemical found in passion fruit seeds. To clarify the effects of PIC on obesity-induced inflammation in adipose tissue, we investigated the anti-inflammatory activity of PIC-related compounds (PIC, RES, and metabolites from PIC) in culture models of obese adipose tissue. Lipopolysaccharide (LPS) and conditioned medium from 3T3-L1 adipocytes (3T3-L1-CM) enhanced proinflammatory gene expression and synthesis of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in RAW264.7 macrophages. Although each compound inhibited the mRNA expression of iNOS (inducible NO synthase), TNF-α, and IL-6, PIC potently inhibited them, and 30 µmol/L PIC suppressed the LPS- and 3T3-L1-CM-induced mRNA expression of iNOS (70.4% and 69.2% suppression, respectively), TNF-α (42.6% and 47.0% suppression), and IL-6 (27.3% and 42.1% suppression). PIC also significantly suppressed production of NO (80.3% suppression) and inflammatory cytokines (TNF-α; 33.7% suppression, IL-6; 66.5% suppression). Furthermore, PIC was found to rescue the uncoupling protein 1 mRNA expression induced by isoproterenol in 10T1/2 adipocytes, which was suppressed by LPS-activated macrophages. These results suggest that PIC may attenuate the pathologic inflammation triggered by adipose tissues.

Piceatannol is superior to resveratrol in promoting neural stem cell differentiation into astrocytes.

Piceatannol (3,3',4',5-trans-tetrahydroxystilbene) is a polyphenolic compound abundant in the seeds of passion fruit (Passiflora edulis). Piceatannol is an analogue of resveratrol (3,4',5-trans-trihydroxystilbene) and shares the structural motif and biological activities such as activation of SIRT1. Several studies have shown that piceatannol is more potent than resveratrol. In this study, we examined the effects of piceatannol on neural stem cell differentiation into astrocytes compared with those of resveratrol. At a concentration of 2.5 µM, piceatannol promoted astrocyte differentiation, while resveratrol had no effect at this concentration. Furthermore, we found that oral administration of piceatannol increased the number of astrocytes in the brains of adult mice, while resveratrol administration showed no effects. These results suggest that piceatannol has a superior effect to resveratrol in promoting astrocyte differentiation.

Vascular- and hepato-protective effects of passion fruit seed extract containing piceatannol in chronic high-fat diet-fed rats.

The effects of chronic administration of piceatannol-enriched (9.5% w/w) passion fruit seed extract (PFSE) on the cardiovascular damage induced in a high-fat (HF) diet-fed model of Fischer 344 rats were evaluated. Rats were fed the control, HF, or HF diets containing PFSE (0.5% w/w) for 16 weeks, and the effects of the various diets on the tissue weight, serum lipid profile, hepatic fibrosis, hepatic ductular reaction, cardiac function and aortic ring reactivity were examined. HF diet-fed rats developed signs of cardiovascular disease with abnormal serum profiles compared to control diet-fed rats. PFSE supplementation improved the liver hypertrophy and hepatic histology of the HF diet-fed rats. In addition, the triglyceride and cholesterol levels, platelet aggregation, cardiac function, and acetylcholine-mediated relaxation of the aortic ring were improved. These results suggest that the chronic intake of PFSE containing piceatannol prevents HF diet-induced cardiovascular disease in rats.

Administration of Piceatannol Complexed with α-Cyclodextrin Improves Its Absorption in Rats.

Piceatannol is polyphenolic antioxidant found in passion fruit (Passiflora edulis) seeds. The aim of this study was to improve the absorption of piceatannol using α-cyclodextrin (αCD). The solubility of piceatannol in neutral and acidic solutions increased in an αCD concentration-dependent manner. The maximum plasma concentration of intact piceatannol and the time-to-maximum plasma concentration of O-methylated piceatannol metabolites increased in rats administered αCD-piceatannol inclusion complexes (PICs). Administering the αCD inclusion complexes significantly increased the area under the concentration-time curve of total stilbene derivatives (0-3 h) in terms of the total amount of intact piceatannol, O-methylated piceatannol, conjugated piceatannol, and isorhapontigenin. Gastrointestinal ligation experiments demonstrated that substantially higher levels of piceatannol metabolites were present in the lower intestine (the ileum) at 1 h postintragastric αCD-PICs administration as compared to those observed following piceatannol administration only. These results suggested that αCD enhanced piceatannol movement and absorption in the small intestine.

Enhanced glucose tolerance by intravascularly administered piceatannol in freely moving healthy rats.

Piceatannol is a phytochemical in the seeds of passion fruit that has a hypoglycemic effect when orally administered. To elucidate the contribution of intact and metabolites of piceatannol after gastro-intestinal absorption to hypoglycemic effect, we examined the influence of piceatannol and isorhapontigenin on blood glucose concentrations during fasting and glucose tolerance tests by administering them intravascularly to freely moving healthy rats. We found that intravascularly administered piceatannol reduced the blood glucose concentrations during both fasting and glucose tolerance tests, but isorhapontigenin did not during either of them. Furthermore, we found that piceatannol increased the insulinogenic index during glucose tolerance tests and that piceatannol had no influence on insulin sensitivity by performing hyperinsulinemic euglycemic clamping tests. These results suggest that piceatannol orally intaken may enhance glucose tolerance by the effect of intact piceatannol through enhanced early-phase secretion of insulin. Therefore, oral intake of piceatannol might contribute to proper control of postprandial glycemic excursions in healthy subjects.

Piceatannol lowers the blood glucose level in diabetic mice.

We previously found that passion fruit (Passiflora edulis) seeds contained a high amount of piceatannol (3,5,3',4'-trans-tetrahydroxystilbene), a natural analog of resveratrol (3,5,4'-trans-trihydroxystilbene). Resveratrol has been proposed as a potential anti-metabolic disorder compound, by its activation of sirtuin and AMP-activated protein kinase. Many reports show that resveratrol ameliorates diet-induced obesity and insulin resistance. However, it is not known whether piceatannol also affects diet-induced obesity. We explored the effect of piceatannol on high fat diet-fed mice. The results showed that piceatannol did not affect high fat diet-induced body weight gain or visceral fat gain in mice. However, piceatannol did reduce fasting blood glucose levels. Furthermore, to explore the potential of passion fruit seed extract containing piceatannol as a functional food, passion fruit seed extract was administered in a genetic diabetic mouse model (db/db mice). Single administration of passion fruit seed extract, as well as piceatannol reduced the blood glucose levels of these db/db mice. These results suggest that piceatannol and passion fruit seed extract may have potential application in the prevention of diabetes.

Reliability and validity assessment of the Japanese version of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

OBJECTIVE: Delirium may lead to adverse outcomes in patients with serious conditions, but is often under-diagnosed due to inadequate screening. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is an established method for assessing delirium in the ICU. The validity and reliability of the Japanese version of the CAM-ICU has not, however, been verified, and we undertook this study to verify these parameters. RESEARCH METHODOLOGY: CAM-ICU validity and reliability were assessed in two Japanese ICUs. Using the evaluation of the DMS-IV-TR in the psychiatrists group as the standard criteria for delirium diagnosis, we compared the evaluation of the Japanese version of the CAM-ICU between the research nurses group and the staff nurses group. RESULTS: According to DSM-IV-TR criteria, the prevalence of delirium was 22.0%, and according to CAM-ICU delirium was found in 22.0% with Research Nurses and 19.5% with Staff Nurses. CAM-ICU sensitivity ratings were 83% and 78%, while their specificity ratings were 95% and 97%, respectively. The Kappa inter-rater reliability was good (κ=0.85), and Cronbach's alpha coefficient was 0.69 (95% CI: 0.57-0.79). Mean rating time for the CAM-ICU was 2.5-2.8 minutes for Research Nurses and Staff Nurses, respectively. CONCLUSION: The Japanese version of the CAM-ICU has comparable validity and reliability as a delirium assessment tool in surgical patients in two Japanese ICUs. With training, CAM-ICU can be incorporated into daily clinical practice.

Piceatannol and its metabolite, isorhapontigenin, induce SIRT1 expression in THP-1 human monocytic cell line.

Piceatannol is a phytochemical that is present in large amounts in passion fruit (Passiflora edulis) seeds, and is an analog of resveratrol. Recently, the absorption and metabolism of piceatannol were investigated in rats, and isorhapontigenin, O-methyl piceatannol, was detected as a piceatannol metabolite in rat plasma. To elucidate the function of piceatannol and its metabolites, we investigated the expression of sirtuin 1 (SIRT1) in THP-1 monocytic cells after treatment with piceatannol and its metabolites, and compared their effects with those of resveratrol and its metabolites. Piceatannol and resveratrol upregulated the expression levels of SIRT1 mRNA and SIRT1 protein. An extract of passion fruit seeds, which contained high levels of piceatannol, also upregulated SIRT1 mRNA expression. As for the metabolites, isorhapontigenin upregulated SIRT1 mRNA expression, whereas resveratrol glucuronides and sulfate did not affect SIRT1 expression. These findings indicate that after intake of piceatannol, not only piceatannol itself, but also its metabolite, isorhapontigenin, contributed to the upregulation of SIRT1 expression.

Absorption and metabolism of piceatannol in rats.

Piceatannol (trans-3,3',4,5'-tetrahydroxystilbene), a natural analogue of resveratrol, has multiple biological functions. Nevertheless, piceatannol's biological fate is yet to be determined. In this study, we evaluated the absorption and metabolism of piceatannol in rats. Furthermore, the area under the plasma concentration curves (AUC) and metabolic pathway of piceatannol were compared with those of resveratrol. We determined the plasma concentrations of piceatannol, resveratrol, and their respective metabolites following their intragastric administration. Resveratrol metabolites were only conjugates, whereas piceatannol metabolites were piceatannol conjugates, O-methyl piceatannol, and its conjugates. The AUC for piceatannol, resveratrol, and their metabolites increased in a dose-dependent manner (90-360 µmol/kg). The AUC for total piceatannol was less than that for total resveratrol, whereas the AUC for piceatannol (8.6 µmol·h/L) after piceatannol and resveratrol coadministration was 2.1 times greater than that for resveratrol (4.1 µmol·h/L). The greater AUC for piceatannol was a result of its higher metabolic stability.

Comparison of (-)-epigallocatechin-3-O-gallate (EGCG) and O-methyl EGCG bioavailability in rats.

(-)-Epigallocatechin-3-O-(3-O-methyl)gallate (EGCG3″Me) and (-)-epigallocatechin-3-O-(4-O-methyl)gallate (EGCG4″Me) are O-methyl derivatives of (-)-epigallocatechin-3-O-gallate (EGCG) present in tea cultivars such as Benifuuki. Although O-methyl EGCGs have various bioactivities, their bioavailabilities have not been determined. In this study, we compared the bioavailability of EGCG and O-methyl EGCGs in rats, and clarified the pharmacokinetics of O-methyl EGCGs. Following oral administration (100 mg/kg), the areas under the concentration-time curves (AUCs) for EGCG, EGCG3″Me, and EGCG4″Me were 39.6 ± 14.2 µg·h/L, 317.2 ± 43.7 µg·h/L, and 51.9 ± 11.0 µg·h/L, respectively. The AUC after intravenous administration (10 mg/kg) was 2772 ± 480 µg·h/L for EGCG, 8209 ± 549 µg·h/L for EGCG3″Me, and 2465 ± 262 µg·h/L for EGCG4″Me. The bioavailability of EGCG3″Me (0.38%) was the highest (EGCG: 0.14% and EGCG4″Me: 0.21%). The distribution volume of EGCG3″Me (0.26 ± 0.02 L/kg) was the lowest (EGCG: 0.94 ± 0.16 L/kg and EGCG4″Me: 0.93 ± 0.14 L/kg). These results suggested that the higher AUC of EGCG3″Me after oral administration was related to its high bioavailability and low distribution volume. These findings supported the stronger bioactivity of EGCG3″Me in vivo.

The protective effects of piceatannol from passion fruit (Passiflora edulis) seeds in UVB-irradiated keratinocytes.

The use of naturally occurring botanicals with substantial antioxidant activity to prevent photoageing is receiving increasing attention. We have previously identified piceatannol and scirpusin B, which is a dimer of piceatannol, as strong antioxidants that are present in passion fruit (Passiflora edulis) seeds. In the present study, the effects of passion fruit seed extract, piceatannol, and scirpusin B on human keratinocytes were investigated. The passion fruit seed extract and piceatannol upregulated the glutathione (GSH) levels in keratinocytes in a dose-dependent manner, indicating that piceatannol is an active component of the passion fruit seed extract in keratinocytes. The pretreatment with piceatannol also suppressed the UVB-induced generation of reactive oxygen species (ROS) in the keratinocytes. In addition, the transfer of the medium from the UVB-irradiated keratinocytes to non-irradiated fibroblasts enhanced matrix-metalloproteinase (MMP)-1 activity, and this MMP-1 induction was reduced when the keratinocytes were pretreated with piceatannol. These results suggest that piceatannol attenuates the UVB-induced activity of MMP-1 along with a reduction of ROS generation in keratinocytes. Thus, piceatannol and passion fruit seed extract containing high amounts of piceatannol are potential anti-photoageing cosmetic ingredients.

Hydroxylation of (-)-epigallocatechin-3-O-gallate at 3'', but not 4'', is essential for the PI3-kinase/Akt-dependent phosphorylation of endothelial NO synthase in endothelial cells and relaxation of coronary artery rings.

(-)-Epigallocatechin-3-O-gallate (EGCg) has been shown to induce endothelium-dependent nitric oxide (NO)-mediated relaxation via the redox-sensitive Src/PI3-kinase/Akt-dependent phosphorylation of endothelial NO synthase (eNOS). Although the presence of 8 hydroxyl functions, mainly on B and D rings, is essential for the EGCg-induced activation of eNOS, the relative role of each individual hydroxyl function still remains unclear. This study examined the effect of selective replacement of hydroxyl functions by methoxy moieties on either the B or D ring on the EGCg-induced phosphorylation of Akt and eNOS, formation of reactive oxygen species (ROS) and NO in cultured coronary artery endothelial cells, and endothelium-dependent relaxation of coronary artery rings. Replacement of a single hydroxyl by the methoxy group on position 3', 4' or 4'' affected little the EGCg-induced phosphorylation of Akt and eNOS, formation of ROS and NO in endothelial cells, and induction of endothelium-dependent relaxations. In contrast, the single methylation at position 3'' and the double methylation at both positions 3' and 4' reduced markedly the phosphorylation of Akt and eNOS, the formation of ROS and NO in endothelial cells and the relaxation of artery rings. These findings suggest that the hydroxyl group at the 3'' position of the gallate ring is essential and, also, to some extent, the two hydroxyl groups at positions 3' and 4', for the EGCg-induced redox-sensitive activation of eNOS leading to the subsequent NO-mediated vascular relaxation.

Effect of long-term piceatannol treatment on eNOS levels in cultured endothelial cells.

Piceatannol (3, 3', 4, 5'-tetrahydroxy-trans-stilbene) is a naturally occurring phytochemical found in passion fruit (Passiflora edulis) seeds. Previously, we demonstrated that piceatannol has acute vasorelaxant effects in rat thoracic aorta. It was suggested that endothelial NO synthase (eNOS) might be involved in piceatannol-induced acute vasorelaxation. Here, we investigated the expression of eNOS in EA.hy926 human umbilical vein cells after long-term treatment with piceatannol, and compared this effect with that of resveratrol, an analog of piceatannol. Long-term treatment with piceatannol up-regulated eNOS mRNA expression and increased eNOS protein expression in a dose-dependent manner. Moreover, piceatannol increased the levels of phosphorylated eNOS. Treatment with resveratrol also increased eNOS expression, but to a lesser degree than piceatannol. These findings indicate that piceatannol may improve vascular function by up-regulating eNOS expression.

Identification of the strong vasorelaxing substance scirpusin B, a dimer of piceatannol, from passion fruit (Passiflora edulis) seeds.

Piceatannol is present in passion fruit (Passiflora edulis) seeds in high amounts. In this study, we isolated the second major polyphenolic compound of passion fruit seeds and identified it as scirpusin B, which is a dimer of piceatannol. We investigated the antioxidant activities and vasorelaxing effects of these polyphenols. Their antioxidant effects were measured using an in vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and their vasorelaxant effects were determined ex vivo in rat thoracic aorta. Both polyphenolic compounds exhibited potent antioxidant activities and significant vasorelaxant effects in endothelium-intact aortas. More specifically, scirpusin B exerted a greater antioxidant activity and vasorelaxant effect compared with that of piceatannol. Additionally, the vasorelaxation effects of the compounds were induced via the NO derived from the endothelium. This study provides the possibility that polyphenols in passion fruit seeds are effective against cardiovascular diseases (CVDs).

Usefulness of pharmacist-assisted screening and psychiatric referral program for outpatients with cancer undergoing chemotherapy.

OBJECTIVE: Major depressive disorder (MDD) and adjustment disorder (AD) are common psychiatric disorders in cancer patients but are often overlooked in clinical oncology settings. We introduced a clinical screening program utilizing the Distress and Impact Thermometer (DIT) to identify MDD and AD in cancer outpatients receiving chemotherapy. This study assessed the usefulness of the screening program. METHODS: Pharmacists administered the DIT to consecutive patients undergoing chemotherapy at an outpatient clinic. Psychiatric treatment was recommended to all the patients with positive screening results. The proportion of patients referred to the Psychiatric Service during the program period was then compared with that during a usual care period. RESULTS: Of the 520 patients who started chemotherapy during the 6-month program period, 5.0% (26/520) were referred to the Psychiatric Service and 2.7% (15/520) were diagnosed as having MDD or AD. No statistically significant difference in the referral rates was observed between the two periods (2.7 vs 1.0%, p = 0.46). However, the period from the first chemotherapy treatment until the visit to the Psychiatric Service was significantly shorter during the program period than during the period of usual care (12.9±13.2 days vs 55.6±17.6 days, p<0.001). CONCLUSIONS: The proportion of patients referred to the Psychiatric Service for the treatment of MDD or AD during the program period was not different from that during the usual care period. However, the program was useful for introducing psychiatric treatment at an earlier stage. Further modifications to the program to improve the referral rate are necessary.