Vascular homeostasis is regulated by complex interactions between many vascular cell components, including endothelial cells, vascular smooth muscle cells (VSMCs), adventitial inflammatory cells, and autonomic nervous system. The balance between oxidant and antioxidant systems determines intracellular redox status, and their imbalance can cause oxidative stress. Excessive oxidative stress is one of the important stimuli that induce cellular damage and dysregulation of vascular cell components, leading to vascular diseases through multiple pathways. Cyclophilin A (CyPA) is one of the causative proteins that mediate oxidative stress-induced cardiovascular dysfunction. CyPA was initially discovered as the intracellular receptor of the immunosuppressive drug cyclosporine 30 years ago. However, recent studies have established that CyPA is secreted from vascular cell components, such as endothelial cells and VSMCs. Extracellular CyPA augments the development of cardiovascular diseases. CyPA secretion is regulated by Rho-kinase, which contributes to the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. We recently reported that plasma CyPA levels are significantly higher in patients with coronary artery disease, which is associated with increased numbers of stenotic coronary arteries and the need for coronary intervention in such patients. Furthermore, we showed that the vascular erythropoietin (Epo)/Epo receptor system plays an important role in production of nitric oxide and maintenance of vascular redox state and homeostasis, with a potential mechanistic link to the Rho-kinase-CyPA pathway. In this article, I review the data on the protective role of the vascular Epo/Epo receptor system and discuss the roles of the CyPA/Rho-kinase system in cardiovascular diseases.
Stroke is one of the leading causes of morbidity and long-term disability worldwide, and post-stroke depression (PSD) is a common and serious psychiatric complication of stroke. PSD makes patients have more severe deficits in activities of daily living, a worse functional outcome, more severe cognitive deficits and increased mortality as compared to stroke patients without depression. Therefore, to reduce or prevent mental problems of stroke patients, psychological treatment should be recommended. Literature and art therapy are highly effective psychological treatment for stroke patients. Literature therapy divided into poetry and story therapy is an assistive tool that treats neurosis as well as emotional or behavioral disorders. Poetry can add impression to the lethargic life of a patient with PSD, thereby acting as a natural treatment. Story therapy can change the gloomy psychological state of patients into a bright and healthy story, and therefore can help stroke patients to overcome their emotional disabilities. Art therapy is one form of psychological therapy that can treat depression and anxiety in stroke patients. Stroke patients can express their internal conflicts, emotions, and psychological status through art works or processes and it would be a healing process of mental problems. Music therapy can relieve the suppressed emotions of patients and add vitality to the body, while giving them the energy to share their feelings with others. In conclusion, literature and art therapy can identify the emotional status of patients and serve as a useful auxiliary tool to help stroke patients in their rehabilitation process.
Mucinous cystadenoma is a rare benign neoplasm and is usually discovered incidentally. Pleuritis and pericarditis, inflammation of the pleura and pericardium, may represent manifestations of autoimmune disorders especially in female subjects. We report a patient with polyserositis that was resolved after removal of the mucinous cystadenoma. To the best of our knowledge, this is a first report describing pleuritis and pericarditis as an initial presentation of mucinous cystadenoma of an appendix. A forty-year-old Caucasian female patient with a history of pleuritis and recurrent pericarditis was admitted to the hospital due to acute abdomen. At that time she was taking indomethacin and colchicine due to pericarditis that was controlled only with the combination of these two drugs. The patient had elevated erythrocyte sedimentation rate (ESR), increased C-reactive protein (CRP) and normocytic anemia. Immunological tests, including antinuclear antibody, anti-neutrophil cytoplasmic antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies, were repeatedly negative. Emergency surgery revealed acute appendicitis with perforation and subsequent diffuse peritonitis. Histopathological examination showed acute appendicitis and mucinous cystadenoma. Following the surgery the patient did not take any drugs. Fourteen months later the patient was symptom free. Pleuritis and pericarditis in female patients are most often associated with autoimmune diseases. We assume that increased ESR and CRP with anemia detected in the patient may reflect the altered immunity that is due to mucinous cystadenoma. We believe that this report has a broader clinical impact, implying that benign tumor could alter immunity, which can lead to unusual presentation such as polyserositis.
Both osteoporosis and tooth loss are health concerns that affect many older people. Osteoporosis is a common skeletal disease of the elderly, characterized by low bone mass and microstructural deterioration of bone tissue. Chronic mild stress is a risk factor for osteoporosis. Many studies showed that tooth loss induced neurological alterations through activation of a stress hormone, corticosterone, in mice. In this study, we tested the hypothesis that tooth loss early in life may accelerate age-related bone deterioration using a mouse model. Male senescence-accelerated mouse strain P8 (SAMP8) mice were randomly divided into control and toothless groups. Removal of the upper molar teeth was performed at one month of age. Bone response was evaluated at 2, 5 and 9 months of age. Tooth loss early in life caused a significant increase in circulating corticosterone level with age. Osteoblast bone formation was suppressed and osteoclast bone resorption was activated in the toothless mice. Trabecular bone volume fraction of the vertebra and femur was decreased in the toothless mice with age. The bone quality was reduced in the toothless mice at 5 and 9 months of age, compared with the age-matched control mice. These findings indicate that tooth loss early in life impairs the dynamic homeostasis of the bone formation and bone resorption, leading to reduced bone strength with age. Long-term tooth loss may have a cumulative detrimental effect on bone health. It is important to take appropriate measures to treat tooth loss in older people for preventing and/or treating senile osteoporosis.
Chewing xylitol gum provides oral health benefits including inhibiting Streptococcus mutans plaque. It is thought to be especially effective in conditions where it is difficult to perform daily oral cleaning. Our study aim was to determine the effects of chewing xylitol gum on self-rated and objective oral health status under a condition interfering with oral hygiene maintenance. A randomized controlled intervention trial was conducted on 55 healthy ≥ 20-year-old men recruited from the Japan Ground Self Defense Force who were undergoing field training. Participants were randomly assigned to a test group (chewing gum; n = 27) or a control group (no gum; n = 28) and the researchers were blinded to the group assignments. The Visual Analog Scale (VAS) scores of oral conditions subjectively evaluated oral health, and the stimulated salivary bacteria quantity objectively evaluated oral health 1 day before field training (baseline) and 4 days after the beginning of field training (follow-up). VAS scores of all three oral conditions significantly increased in the control group (malodor: p < 0.001; discomfort: p < 0.001; dryness: p < 0.001), but only two VAS scores increased in the test group (malodor: p = 0.021; discomfort: p = 0.002). The number of salivary total bacteria significantly increased in the control group (p < 0.01), while no significant change was observed in the test group (p = 0.668). Chewing xylitol gum positively affects self-rated and objective oral health status by controlling oral hygiene under conditions that interfere with oral hygiene maintenance.
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical synovitis predominantly involving the wrists, and is associated with marked pitting edema of the dorsum of the hands. Although the etiology of RS3PE syndrome is still unknown, several putative associations with malignancies and hematological disorders have been reported. Myelodysplastic syndrome (MDS) is characterized by infective hematopoiesis with possible transformation to leukemia; however, an association between RS3PE syndrome and MDS has been rarely reported. Here, we describe a 67-year-old man with MDS with refractory anemia who developed RS3PE syndrome 3 months after the diagnosis of MDS. The patient presented with polyarthritis with pitting edema at the dorsum of the hands, the elevated serum levels of C-reactive protein and a proinflammatory cytokine, interleukin-6, and the elevated plasma levels of vascular endothelial growth factor (VEGF). VEGF has been shown to be involved in the pathogenesis of RS3PE syndrome. Treatment with low doses of corticosteroids resulted in the regression of polyarthritis and pitting edema of the dorsum of the hands, as well as a reduction in the elevated levels of plasma VEGF. Partial resolution of refractory anemia was also observed with steroid therapy. In summary, RS3PE syndrome developed shortly after MDS was identified in this patient. The sequence of clinical events suggests that MDS-mediated immunological abnormalities including inflammatory cytokine induction may be responsible for the association between MDS and RS3PE syndrome. Patients with RS3PE syndrome should be screened for hematological disorders that promote proinflammatory mediators.
Quality of life, comfort, and wellbeing during pregnancy are essential for every country in the world. Pregnancy is considered a preparation period for becoming a mother. Maternal role development, including confidence and satisfaction as a mother, is important in the transition to motherhood. Negative psychosocial affect, such as increased anxiety and distress, during pregnancy adversely influences the childbirth experience and childcare, which contributes to postpartum depression. However, the impact of positive feelings on the maternal role development remains unclear. Therefore, the study purpose was to clarify the relationship between comfort in late pregnancy and maternal role attainment and childcare during early postpartum. We designed a descriptive, longitudinal, correlational study by using the Prenatal Comfort Scale, the Postpartum Maternal Role Confidence Scale, and the Postpartum Maternal Satisfaction Scale. Among 339 participants who had received care at a university hospital located in Sendai city in Japan, 215 subjects completed the longitudinal study by answering a questionnaire for the respective Scale late in their pregnancy or during early postpartum. The subjects consisted of 114 primipara (32.0 ± 5.4 years) and 101 multipara (33.4 ± 4.9 years). In primipara, comfort with motherhood was significantly correlated with maternal confidence regarding knowledge and childcare skills and maternal satisfaction. In multipara, comfort in late pregnancy was related to maternal confidence and satisfaction. Positive affect was related to maternal confidence and maternal satisfaction in early postpartum. Therefore, a prenatal nursing intervention helps women become more comfortable with impending motherhood, thereby promoting maternal role attainment after delivery.
Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD). In adult patients, liver transplantation (LT) is the treatment of choice for end-stage liver disease secondary to NASH. However, little information is available regarding outcomes of LT in pediatric patients with NASH. We describe here a pediatric patient with NASH associated with hypopituitarism who underwent living donor liver transplantation (LDLT). An 11-year-old boy was diagnosed with a pituitary tumor, which was removed by trans-interhemispheric approach following bifrontal craniotomy. Histopathological examination revealed a mature teratoma. Eighteen months later, magnetic resonance imaging showed recurrence of the pituitary tumor, which was found to be a germinoma. He underwent 3 months of chemoradiotherapy, with a complete response. He gradually became obese, with elevated transaminase levels. At age 15 years, he developed fatigue and dyspnea and was found to have liver cirrhosis secondary to NASH with severe hepatopulmonary syndrome. He underwent LDLT using a right liver graft from his mother. Twelve months later, abdominal computed tomography showed recurrence of NAFLD. Five years after the LDLT, transaminases were slightly elevated. Growth hormone replacement therapy was started, reducing transaminase levels to their normal ranges. Ten years after LDLT, fatty liver remains stable, although his body mass index has not been reduced. Growth hormone replacement therapy may be effective in graft maintenance. This is the first case report of a patient with maintained stable liver function 10 years after LDLT for pediatric NASH.
Hepcidin is a key regulator of mammalian iron metabolism and mainly produced by the liver. Hepcidin excess causes iron deficiency and anemia by inhibiting iron absorption from the intestine and iron release from macrophage stores. Anemia is frequently complicated with heart failure. In heart failure patients, the most frequent histologic appearance of liver is congestion. However, it remains unclear whether liver congestion associated with heart failure influences hepcidin production, thereby contributing to anemia and functional iron deficiency. In this study, we investigated this relationship in clinical and basic studies. In clinical studies of consecutive heart failure patients (n = 320), anemia was a common comorbidity (41%). In heart failure patients without active infection and ongoing cancer (n = 30), log-serum hepcidin concentration of patients with liver congestion was higher than those without liver congestion (p = 0.0316). Moreover, in heart failure patients with liver congestion (n = 19), the anemia was associated with the higher serum hepcidin concentrations, which is a type of anemia characterized by induction of hepcidin. Subsequently, we produced a rat model of heart failure with liver congestion by injecting monocrotaline that causes pulmonary hypertension. The monocrotaline-treated rats displayed liver congestion with increase of hepcidin expression at 4 weeks after monocrotaline injection, followed by anemia and functional iron deficiency observed at 5 weeks. We conclude that liver congestion induces hepcidin production, which may result in anemia and functional iron deficiency in some patients with heart failure.