Perilla frutescens seed oil combined with Anredera cordifolia leaf powder attenuates age-related cognitive decline by reducing serum triglyceride and glucose levels in healthy elderly Japanese individuals: a possible supplement for brain health.

We have shown that Anredera cordifolia extract improves learning and memory in a senescence-accelerated mouse model, and that α-linolenic acid (ALA)-rich Perilla frutescens seed oil (PO) improves brain function in healthy Japanese adults and elderly individuals. Herein, we present a 12-month, randomised, double-blind, parallel-armed intervention trial examining the effects of PO supplementation alone or in combination with A. cordifolia leaf powder on brain function in healthy elderly Japanese individuals. Participants were randomly divided into two groups: the PO group received 1.47 mL PO (0.88 g ALA) daily via soft gelatine capsules, and the POAC group received 1.47 mL PO and 1.12 g A. cordifolia leaf powder (1.46 mg vitexin and 1.12 mg adenosine) daily. After 12 months of intervention, the POAC group showed generally higher cognitive index scores than the PO group. The beneficial effects of combined supplementation on cognitive function were associated with increased ALA and eicosapentaenoic acid levels in red blood cell plasma membranes, increased serum biological antioxidant potential, and decreased serum triglyceride, glucose, and N-(epsilon)-carboxymethyl-lysine (CML), an advanced glycation end-product and biochemical marker of oxidative stress levels. The effects of combined supplementation on cognitive function also showed a significant negative correlation with serum CML levels after 12 months of intervention. Our findings suggest that combined long-term supplementation with PO and A. cordifolia more effectively ameliorates age-related cognitive decline than PO alone. These findings may serve as a basis for the development of new supplements for brain health. Clinical Trial Registry, UMIN000040863.

Complement Activation in Patients With Heat-Related Illnesses: Soluble CD59 Is a Novel Biomarker Indicating Severity of Heat-Related Illnesses.

OBJECTIVES: Although multiple organ dysfunction syndrome (MODS) is the main cause of death in patients with heat-related illnesses, its underlying pathophysiological mechanism remains elusive. Complement activation is considered one of the main causes of MODS in patients with sepsis and trauma. Considering the pathophysiological similarity of heat related-illnesses with sepsis and trauma, the complement system might be activated in patients with heat-related illnesses as well. Our aim was to investigate whether excessive complement activation occurs in patients with heat-related illnesses. DESIGN: Prospective observational study. SETTING: Emergency department in the university hospital. PATIENTS: Thirty-two patients with heat-related illnesses and 15 age-matched healthy controls were enrolled in this study. INTERVENTIONS: Blood samples were collected from the study subjects for the measurement of complement factors. MEASUREMENTS AND MAIN RESULTS: Complement component 3a (C3a), complement component 5a (C5a), C5b-9, complement factor B (Ba), Factor H, and soluble CD59 in plasma were measured. The levels of C3a, C5a, C5b-9, and Ba significantly increased in patients with heat-related illnesses on day 0 compared with those in the healthy controls. Soluble CD59 was significantly high in patients with heat-related illnesses on day 0 and showed a correlation with the severity of the condition (Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and staging scores), Japanese Association for Acute Medicine disseminated intravascular coagulation scores, and the coagulation system (prothrombin time and fibrin degradation products). CONCLUSIONS: The complement system was activated in patients with heat-related illnesses, suggesting that it is one of the causes of MODS. Soluble CD59 may be a potent biomarker for the severity of heat-related illnesses.

Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly.

Perilla (Perilla frutescens) seed oil (PO), rich in α-linolenic acid (ALA), can improve cognitive function in healthy elderly Japanese people. Here, supplements containing either PO alone or PO with nobiletin-rich air-dried immature ponkan powder were examined for their effects on cognitive function in 49 healthy elderly Japanese individuals. Patients were enrolled in a 12-month randomized, double-blind, parallel-armed study. Randomized participants in the PO group received soft gelatin capsules containing 1.47 mL (0.88 g of ALA) of PO daily, and those in the PO + ponkan powder (POPP) group received soft gelatin capsules containing both 1.47 mL of PO and 1.12 g ponkan powder (2.91 mg of nobiletin) daily. At the end of intervention, the POPP group showed significantly higher cognitive index scores than the PO group. The pro-cognitive effects of POPP treatment were accompanied by increases in ALA and docosahexaenoic acid levels in red blood cell plasma membranes, serum brain-derived neurotropic factor (BDNF) levels, and biological antioxidant potential. We demonstrate that 12-month intervention with POPP enhances serum BDNF and antioxidant potential, and may improve age-related cognitive impairment in healthy elderly people by increasing red blood cell ω-3 fatty acid levels. Clinical Trial Registry, UMIN000040863.

Influence of Ultra-High Hydrostatic Pressurizing Brown Rice on Cognitive Functions and Mental Health of Elderly Japanese Individuals: A 2-Year Randomized and Controlled Trial.

Brown rice contains many ingredients that might protect against cognitive decline and Alzheimer's disease. However, brown rice is very hard, difficult to cook, and is poorly digested; thus, it is difficult to eat long-term. To solve these problems, ultra-high hydrostatic pressurizing brown rice (UHHPBR) was prepared. We investigated the effects of dietary UHHPBR administration for 24 mo on cognitive function and mental health in the elderly. Healthy elderly participants (n=52) were randomized into UHHPBR and polished white rice (WR) groups. The UHHPBR group consumed 100 g of UHHPBR per day for 24 mo and the WR group consumed white rice. At baseline, and after 12 and 24 mo, cognitive functions were assessed using the Revised Hasegawa's Dementia Scale, Mini-Mental State Examination, Frontal Assessment Battery (FAB), and the Cognitive Assessment for Dementia, iPad version (CADi). Mental health condition was also assessed using the Apathy Scale and the Zung Self-Rating Depression Scale, and serum biochemical parameters were determined. From baseline to month 24, the mean change in the FAB-sub item 1 scores was higher in the UHHPBR group compared to the WR group. Furthermore, apathy scores decreased, as well as the time required to answer all questions of the CADi, and plasma epinephrine levels increased. These results indicate that a 2-y oral consumption of UHHPBR increases information processing speed (as a measure of cognitive function) and improves apathy in the elderly, suggesting a protective effect of UHHPBR administration against age-related decline in brain cognition and motivation.

Fluorescence imaging of ATP in neutrophils from patients with sepsis using organelle-localizable fluorescent chemosensors.

BACKGROUND: The activation of polymorphonuclear neutrophils (PMNs) plays an important role in sepsis. Previously, we showed that ATP release and feedback via ATP receptors are essential for PMN activation; however, the dynamics remain poorly understood. Two new fluorescent chemosensors, PMAP-1 and MitoAP-1, were developed to detect ATP in the plasma membrane and mitochondria of living cells, respectively. In this study, we aimed to evaluate ATP localization using these chemosensors in PMNs of sepsis patients. METHODS: Live PMNs isolated from 16 sepsis patients and healthy controls (HCs) were stained with these chemosensors and observed by confocal microscopy, and their mean fluorescence intensities (MFIs) were evaluated using flow cytometry. CD11b expression in PMNs was also evaluated. RESULTS: The MFIs of PMAP-1 and MitoAP-1 and CD11b expression in PMNs from sepsis patients on days 0-1 were significantly higher than those of HCs. The MFI of PMAP-1 and CD11b expression on days 3-4 decreased significantly compared to those observed at days 0-1, whereas MitoAP-1 MFI was maintained at a high level. The PMAP-1 MFI was significantly positively correlated with CD11b expression, white blood cell counts, neutrophil counts, and C-reactive protein levels in patients. CONCLUSIONS: The higher MFIs of PMAP-1 and MitoAP-1 in sepsis patients suggest a pivotal role of ATP for PMN activation. The temporal difference in ATP levels suggests that ATP plays different roles in the mitochondria and on the cell surface. These data should contribute to the understanding of the dynamics of ATP in PMNs and help to develop a novel therapy for sepsis.

Leukocyte deformability is a novel biomarker to reflect sepsis-induced disseminated intravascular coagulation.

Aim: Sepsis-induced disseminated intravascular coagulopathy is associated with a high mortality rate. The function and deformability of polymorphonuclear leukocytes change in patients with sepsis. The goal of this study was to characterize the changes in polymorphonuclear leukocyte deformability in patients with sepsis-induced disseminated intravascular coagulopathy and to evaluate the relationship between the severity of disseminated intravascular coagulopathy and the deformability of polymorphonuclear leukocytes. Methods: Thirty-five patients with sepsis-induced disseminated intravascular coagulopathy at our department were enrolled in this study. These patients were diagnosed with severe sepsis and an acute disseminated intravascular coagulopathy score ≥ 4. Blood samples were obtained from these patients on days 1, 3, and 7. Polymorphonuclear leukocyte deformability was measured with a microchannel flow analyzer, and polymorphonuclear leukocyte activity, represented as CD11b, was measured by flow cytometry. In contrast, 14 patients who fulfilled with sepsis criteria but without complicated disseminated intravascular coagulopathy were also entered in this study. Results: In patients with sepsis-induced disseminated intravascular coagulopathy, there was a significant correlation between their Japanese Association for Acute Medicine disseminated intravascular coagulopathy score and polymorphonuclear leukocyte deformability, and CD11b expression. Polymorphonuclear leukocytes became more stiffened and CD11b expression was higher in patients with sepsis-induced disseminated intravascular coagulopathy compared to patients without the condition. Conclusion: Polymorphonuclear leukocyte deformability correlated with the severity of sepsis-induced disseminated intravascular coagulopathy and the response to treatment.

Long-term survival after two surgical resections of peritoneal metastases from hepatocellular carcinoma with an interval of 4 years.

KEY CLINICAL MESSAGE: We propose that surgical resections of peritoneal metastases arising from hepatocellular carcinoma are an option for selected patients with controlled HCC in the liver, and without metastases in other organs, when the complete removal of such metastases can be achieved, especially in the case of patients with normal liver function.

Clinical and pathological evaluation of hypertensive emergency-related nephropathy.

OBJECTIVE: The prognosis of patients with hypertensive emergencies has recently improved dramatically owing to the development of effective antihypertensive therapy. We examined the histological and clinical features of patients with hypertensive emergency-related nephropathy. METHODS: Twelve patients (11 men and one woman) were diagnosed as having hypertensive emergencies with acute renal failure according to the Joint National Committee-7 classification of blood pressure for adults and underwent renal biopsies at our hospital between 1995 and 2008. These patients were enrolled in this retrospective study. RESULTS: The age of the subjects was 40.1±9.8 years. At presentation, the mean systolic/diastolic blood pressure was 232±32/146±12 mmHg and none of the patients were being treated with antihypertensive drugs, although 10 patients had histories of hypertension. The mean serum creatinine level was 6.1±4.7 mg/dL. All 12 patients showed left ventricular hypertrophy on echocardiography. On light microscopy of the renal biopsy specimens, all 12 patients showed onion skin patterns of the arterioles; however, no fibrinoid necrosis of the small arteries was found. Electron microscopy revealed electron-lucent widening of the subendothelial zone of the glomerular capillary walls in seven patients. One of the 12 patients did not respond to medical therapy and required regular dialysis. The other 11 patients responded to treatment. CONCLUSION: An onion skin pattern of the arterioles is the most frequent histological finding in patients with hypertensive emergency-related nephropathy. Long-standing hypertension might contribute to this arteriolar change, since left ventricular hypertrophy was also seen in these patients. With strict control of hypertension using antihypertensive medications, the prognosis of patients with hypertensive emergency-related nephropathy can be improved.

Post-stroke apathy and hypoperfusion in basal ganglia: SPECT study.

BACKGROUND: Although apathy has been reported as one of the neuropsychiatric symptoms following stroke, there are few studies on regional cerebral blood flow (rCBF) in stroke patients with apathy. The present study compared rCBF between apathetic and non-apathetic patients after stroke. METHODS: We recruited 102 patients with cerebral infarction within 1 month after stroke and performed neuropsychiatric assessments that included the apathy scale. rCBF was quantitatively measured using N-isopropyl-p-(123)I-iodoamphetamine single-photon emission computed tomography. RESULTS: Thirty-seven patients (36%) had apathy. The apathetic group showed lower cognitive function and a higher depressive state than the non-apathetic group. rCBF in the basal ganglia was reduced for the apathetic group compared with the non-apathetic group. Furthermore, lesions in the left basal ganglia were associated with hypoperfusion in bilateral basal ganglia and the presence of apathy. CONCLUSION: These findings demonstrate that apathy is a frequent symptom among stroke patients and that hypoperfusion caused by basal ganglia lesions may contribute to post-stroke apathy.