PE859, A Novel Curcumin Derivative, Inhibits Amyloid-ß and Tau Aggregation, and Ameliorates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8.

Aggregation of amyloid-ß (Aß) and tau plays a crucial role in the onset and progression of Alzheimer's disease (AD). Therefore, the inhibition of Aß and tau aggregation may represent a potential therapeutic target for AD. Herein, we designed and synthesized both Aß and tau dual aggregation inhibitors based on the structure of curcumin and developed the novel curcumin derivative PE859. In this study, we investigated the inhibitory activity of PE859 on Aß aggregationin vitro and the therapeutic effects of PE859 on cognitive dysfunction via dual inhibition of Aß and tau aggregation in vivo. PE859 inhibited Aß aggregation in vitro and protected cultured cells from Aß-induced cytotoxicity. Furthermore, PE859 ameliorated cognitive dysfunction and reduced the amount of aggregated Aß and tau in brains of senescence-accelerated mouse prone 8 (SAMP8). These results warrant consideration of PE859 as a candidate drug for AD.

Effect of codon adaptation on codon-level and gene-level translation efficiency in vivo.

BACKGROUND: There is a significant difference between synonymous codon usage in many organisms, and it is known that codons used more frequently generally showed efficient decoding rate. At the gene level, however, there are conflicting reports on the existence of a correlation between codon adaptation and translation efficiency, even in the same organism. RESULTS: To resolve this issue, we cultured Escherichia coli under conditions designed to maintain constant levels of mRNA and protein and subjected the cells to ribosome profiling (RP) and mRNA-seq analyses. We showed that the RP results correlated more closely with protein levels generated under similar culture conditions than with the mRNA abundance from the mRNA-seq. Our result indicated that RP/mRNA ratio could be used as a measure of translation efficiency at gene level. On the other hand, the RP data showed that codon-specific ribosome density at the decoding site negatively correlated with codon usage, consistent with the hypothesis that preferred codons display lower ribosome densities due to their faster decoding rate. However, highly codon-adapted genes showed higher ribosome densities at the gene level, indicating that the efficiency of translation initiation, rather than higher elongation efficiency of preferred codons, exerted a greater effect on ribosome density and thus translation efficiency. CONCLUSIONS: These findings indicate that evolutionary pressure on highly expressed genes influenced both codon bias and translation initiation efficiency and therefore explains contradictory findings that codon usage bias correlates with translation efficiency of native genes, but not with the artificially created gene pool, which was not subjected to evolution pressure.

Psychiatric disorders in patients who lost family members to cancer and asked for medical help: descriptive analysis of outpatient services for bereaved families at Japanese cancer center hospital.

OBJECTIVE: There have been no previous studies about consultation of the bereaved who have lost a loved one to cancer and ask for medical help. The aim of this study was to investigate their basic characteristics and their psychiatric disorders. METHODS: A retrospective study using clinical and background data obtained over 30 months (from April 2007 to September 2009) was conducted at outpatient services for bereaved families at the Department of Psycho-Oncology at Saitama Medical University International Medical Center, Japan. RESULTS: During the period of investigation, 51 patients underwent consultation. The patients were frequently female (P < 0.0001) and the spouse of the deceased. Regarding the psychiatric diagnoses, major depression was the most common (39%), followed by adjustment disorders (28%). CONCLUSIONS: This study revealed basic characteristics and psychiatric disorders of the bereaved who asked for medical help. Most of the patients were women (86.3%) and 86.3% of them received a psychiatric diagnosis. This information is important for both physicians and psychologists since the bereaved who have lost a loved one to cancer often ask for medical help in clinical settings.

Drug-induced akathisia as a cause of distress in spouse caregivers of cancer patients.

OBJECTIVE: Family caregivers of cancer patients suffer from physical, psychological, and social distress and therefore are often referred to as second order patients. Akathisia is a common side effect of antipsychotics and antidepressants that causes great discomfort and even agitation and is often described by patients administered these drugs as the most distressing side effect of their treatment. Several studies of akathisia as a cause of distress in cancer patients have been reported. However, akathisia has not been reported as a cause of distress in family caregivers of cancer patients. METHOD/CASE REPORT: A 74-year-old spouse caregiver who was under treatment for major depressive disorder was not able to visit the hospital where her husband, a terminally ill cancer patient, was being treated. Initially, the spouse caregiver thought that she could not visit the hospital because of the symptoms of her depression and her grief about losing her husband. However, careful clinical examination revealed that she was suffering from akathisia in addition to her grief. RESULTS: Discontinuation of her sulpiride treatment resulted in the disappearance of her akathisia symptoms, and therefore she became able to visit the hospital and care for her terminally ill husband. SIGNIFICANCE OF RESULTS: Drug induced akathisia is a cause of distress in spouse caregivers taking certain drugs. It is important for clinicians to realize that family caregivers might suffer from not only socioeconomic, physical, and psychological problems but also side effects of medication.

Diagnosis and treatment of akathisia in a cancer patient who cannot stand up or sit down, because of poor performance status: factors that make the diagnosis of akathisia difficult, and diagnosis clues.

OBJECTIVE: Akathisia is a common adverse effect of antipsychotics and, less commonly, antidepressants. Akathisia can cause great discomfort and is often described by the patient as a most distressing sensation; however, the condition is often underdiagnosed or misdiagnosed. In oncological settings, neuroleptics and antidepressants that induce akathisia are also administered. However, reports of akathisia in oncology settings are few and a case of akathisia in a bedridden patient has not been reported as far as we know. CASE REPORT: A 72-year-old man with esophageal cancer who could not sit down or stand up was administered 5 mg/day haloperidol to relieve agitation as a symptom of major depressive disorder. Three days after the administration of haloperidol, the agitation had become worse. Careful observation revealed that the patient sometimes showed slight rubbing movement of the lower extremities and slight twisting movements of the body, which were not observed before the administration of haloperidol. The patient moved his body and lower extremities to relieve restlessness, which had developed after the administration of haloperidol. Although symptoms were atypical, akathisia was suspected and discontinuation of haloperidol resolved the symptoms. RESULTS AND SIGNIFICANCE OF RESULTS: In patients with poor performance status, clues leading to the correct diagnosis of akathisia might be absent, which would not be the case in patients who were able to walk, stand up, or sit down. Careful observations of patients before and after the administration of drugs that may cause akathisia may be required to ensure correct diagnosis.

Characteristics, interventions, and outcomes of misdiagnosed delirium in cancer patients.

OBJECTIVE: Although delirium is a common psychiatric complication in cancer patients, it is often not accurately recognized. To date, the characteristics and outcome of misrecognized patients are unclear in the cancer setting. This retrospective study was planned to determine the recognition by oncologists at the psychiatric consultation, characteristics, reversibility and outcome of misrecognized patients with delirium. METHOD: We reviewed charts of 60 patients diagnosed with delirium by the psycho-oncologists who were referred to the psychiatric consultation by the oncologists. Information about demographics, initial assessment by the oncologists, delirium subtype, precipitating factors, intervention for delirium, reversibility, and final status was obtained. RESULTS: Twenty-two among 60 delirious patients were misrecognized by the oncologists at the time of consultation. They were often diagnosed as having anxiety or other psychiatric disorders. Misrecognized participants were significantly younger than accurately recognized cases of delirium. The psychiatrists made suggestions to the oncologists for all the referred patients, even when they were accurately diagnosed with delirium before consultation. For the correctly recognized patients, the main suggestion was pharmacological reevaluation. For the misdiagnosed cases, the psychiatrists suggested a reconsideration of the strategy for cancer treatment and the provision of information to the patient's family members about their condition. SIGNIFICANCE OF RESULTS: Despite its high prevalence, delirium is difficult to diagnose for non-psychiatric physicians. Its detection is important not only to give the best treatment option to cancer patients but also to provide the best opportunity to inform their family about their condition and end-of-life issues.

Bereavement dream? Successful antidepressant treatment for bereavement-related distressing dreams in patients with major depression.

OBJECTIVE: The death of a person is a stressful event. Such stress affects the physical and psychological well-being of the bereaved. As an associated mental disorder, major depressive disorder (MDD) is common. Some dream of the deceased, and these dreams are called bereavement dreams. Some MDD patients also experience dreams. These two types of dreams are sometimes difficult to differentiate. The dream of the bereaved might be only a bereavement-related dream, yet it might be a symptom of MDD. Herein, we report one patient who had distressing dreams after the death of her mother. METHODS: A 63-year-old woman was referred for psychiatric consultation because of generalized fatigue and insomnia. Questioning her about recent events, she said that her mother had died of colonic carcinoma 5 months previously. Two months after the death, she suddenly started dreaming of her mother, getting angry with her almost every night. Generalized fatigue, insomnia, and distressing dreams appeared simultaneously. The dream caused much distress, making her afraid to fall asleep. RESULTS: Her psychiatric features fulfilled the DSM-IV-TR criteria for MDD, single episode. The death of her mother was considered to be one of the causes of MDD. She was administered 25 mg/day of sertraline hydrochloride. After that, her symptoms gradually disappeared, and the frequency of distressing dreams was reduced. Five months later, physical and psychiatric symptoms of MDD were completely resolved. Subsequently, she has not suffered from any distressing dreams of her mother. SIGNIFICANCE OF RESULTS: This case indicates that dreams experienced after the death of a loved one should not be regarded simply as bereavement dreams. Some of the dreams may be symptoms of MDD. If the dreams are the symptoms of MDD, antidepressant treatment as well as psychotherapy may be useful. Therefore, we should avoid regarding symptoms of MDD as reactions to bereavement.

Psychological characteristics and subjective symptoms as determinants of psychological distress in patients prior to breast cancer diagnosis.

GOALS OF WORK: The objective of this study was to determine how psychological characteristics, subjective symptoms, a family history of breast cancer, and age impact psychological distress in outpatients at the first hospital visit prior to breast cancer diagnosis. MATERIALS AND METHODS: Participants were prediagnosed women with complaints of breast symptoms who either came to our hospital directly, or with a referral from another clinic. Patients were asked to complete questionnaires to determine the following: trait anxiety (State-Trait Anxiety Inventory), negative emotional suppression (Courtauld Emotional Control Scale), life stress events (Life Experiences Survey), and psychological distress (Profile of Mood States). We examined subjective symptoms (lumps, pain, abnormal nipple discharge, or deformed nipple) and family history of breast cancer based on answers to the interview sheet filled out by patients on their first visit. We analyzed a total of 154 patients who completed the questionnaires out of 237 eligible patients. MAIN RESULTS: A significant model was obtained by multiple regression analysis (adjusted R (2) = 0.574, p < 0.01) in which the standard partial regression coefficients for trait anxiety, suppression of anxiety, negative life change events, positive life change events, and subjective symptoms were statistically significant (beta = 0.623, 0.133, 0.155, 0.108, and 0.124, respectively; p < 0.05). CONCLUSIONS: Psychological distress prior to diagnosis was higher in patients who had high trait anxiety, suppression of anxiety, many life stress events, and subjective symptoms. In particular, trait anxiety had a large impact on psychological distress, underscoring the need for and importance of adequate psychological care.

Activation syndrome caused by paroxetine in a cancer patient.

Individuals with cancer have two to four times an increased risk of depressive disorders compared to the general population. Depressive symptoms are related to impaired daily life functioning and a rise in health care utilization. Pharmacological treatments for depression are usually effective to reduce depressive symptoms, but sometimes lead to serious adverse reactions. We describe a cancer patient who developed sudden psychological and behavioral abnormalities after administration of the antidepressant paroxetine. Impulsive and aggressive symptoms are a so-called activation syndrome that can cause violent or suicidal tendencies. Palliative care staff should pay close attention to these potentially lethal reactions and make an immediate and correct diagnosis.

A case of respiratory akathisia in a cancer patient: a case report.

OBJECTIVE: It has been reported that akathisia is a neurological side effect induced by antiemetic drugs and/or antipsychotics. Akathisia can occur in any area of the body, but respiratory akathisia is an unusual type of akathisia. Cases of respiratory akathisia in cancer patients taking antiemetic drugs have not previously been reported. METHODS: We report on a case of a cancer patient taking prochlorperazine as an antiemetic drug who experienced dyspnea accompanied by severe restlessness associated with respiration. By administration of biperiden, his restlessness in respiration and dyspnea promptly disappeared. RESULTS: This finding led us to conclude that this cancer patient was experiencing respiratory akathisia. SIGNIFICANCE OF RESULTS: Respiratory akathisia is uncommon. It is important for cancer patients that dyspnea induced by disease progression be ruled out as a cause of the respiratory restlessness. It is necessary to consider the possibility of akathisia in patients that complain of vague anxiety, chest discomfort, or dyspnea following antipsychotic medication.

Detection and treatment of akathisia in advanced cancer patients during adjuvant analgesic therapy with tricyclic antidepressants: case reports and review of the literature.

OBJECTIVE: There is substantial evidence that tricyclic antidepressants are effective in the management of chronic pain, including cancer pain. In oncological settings, these agents are used as adjuvant analgesic drugs. However, cases of akathisia due to tricyclic antidepressants used as adjuvant analgesic therapy have not previously been reported. CASE REPORTS: Two cancer patients experiencing chronic pain who were refractory to nonsteroidal anti-inflammatory drugs and opioids were prescribed amoxapine as an adjuvant analgesic therapy for neuropathic pain. These patients developed inner restlessness and restless physical movements after amoxapine was prescribed. Although symptoms were atypical, akathisia was suspected and discontinuation of amoxapine resolved the symptoms. RESULTS AND SIGNIFICANCE OF RESULTS: Akathisia should be considered in patients receiving adjuvant analgesic therapy with tricyclic antidepressants. Early detection and appropriate treatment will relieve this distressing symptom. Restless movements involving parts of the body other than the legs may be the clue to the diagnosis.