Atopic dermatitis (AD) is a chronic inflammatory skin disease that causes itching. The prevalence of AD in China has increased during the past three decades. Congenital and environmental factors are considered to be involved in the pathogenesis of AD. These factors include skin barrier function defects and immunological abnormalities. In China, AD and eczema are regarded as different diseases, and the diagnosis of AD and eczema are often confused. We analyzed the clinical data of 2,662 adult and adolescent patients (≥ 12 years old) who had suffered from symmetrical eczema for more than two months. One third of the patients were diagnosed as AD, while two thirds were diagnosed as eczema. The patients’ clinical manifestations were quite heterogeneous. Based on the patients’ clinical findings and the concept of AD, we proposed highly sensitive and specific Chinese criteria for adult/adolescent AD. Revised Chinese guidelines for AD were published in 2014. However, a number of problems can still arise during the treatment of AD.
Increased epidermal nerve density is involved in intractable itch in atopic dermatitis. Epidermal innervation is regulated by the balance between nerve growth factors (e.g. NGF) and nerve repulsion factors (e.g. semaphorin 3A, Sema3A) in keratinocytes. Emollient ointment, UV-based therapy, Sema3A ointment and cyclosporine administration decreased the density of epidermal nerve fibers, resulting in improvement of itch. Retinoid-related orphan receptor α (RORα ) agonist and LL-37 which induce Sema3A in keratinocytes may be a useful treatment of atopic dermatitis.
Our skin forms an effective barrier against pathogens and water loss. This is partly mediated by antimicrobial/host defence peptides (AMPs/HDPs). Among these peptides, human β-defensins and LL-37 are the most widely characterized today. They are not only endogenous antibiotics but also display various immunomodulatory functions, including promoting chemotaxis, stimulating the production of cytokines/chemokines, regulating apoptosis, and inducing angiogenesis. Our aim was to review various activities of AMPs/HDPs in keratinocytes, such as regulation of skin barrier function, acceleration of wound healing, promotion of cell differentiation, and inhibition of itching. Therefore, AMPs/HDPs may serve as novel anti-infective and immunomodulatory agents.
Rare fungal infections sometimes are recalcitrant and life-threatening, which bring a big challenge to the clinical management. Recent studies of chronic mucocutaneous candidasis, deep dermatophytosis and some dematiaceous fungal infections have led to many breakthroughs in our understanding of host defense against fungal infections. This review summarizes important findings, including the author’s recent work, of crucial mechanisms that predispose some rare cutaneous fungal infections, including Dectin-1 deficiency, CARD9 deficiency, and STAT1 gain-of-function mutations.
Diffusional magnetic resonance imaging (dMRI) provides indispensable clinical information and is routinely performed in most of all brain MRI study. The dMRI can also uniquely visualize the white matter tracts and is recently highlighted to explore structural connectivity of the brain. Diffusion tensor imaging (DTI) and diffusion tensor tractography are representatives of dMRI. Quantitative analysis of DTI and more sophisticated application of advanced diffusion MRI newly revealed diseas-specific subtle abnormalities in corresponding areas of the brain in many neurological/psychiatric disorders. The dMRI is a promising technique to visualize new aspect of the brain, which no one has never seen before.
Neurons have been considered the most important functional unit of the brain and have attracted the most attention in neurobiology. Neural cells occupy 70%-80% of the whole brain volume, but until now, our current knowledge of neural circuit cannot explain all the neurological conditions of the brain. Thus, it is also important to consider the influence of the extracellular space (ECS) around neural cells, which contains the brain interstitial fluid (ISF). This paper includes the anatomy of the brain ECS under physiological condition, the in vivo measurement techniques of brain ECS, and the divisions of brain ECS. Moreover, the implications of ECS knowledge of basic neuroscience and clinical applications are introduced, including the brain tissue engineering and the local drug delivery via ECS.
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and is caused by the loss of dopaminergic neuronal cells in the substantia nigra pars compacta. Although it is known that genetic factors contribute to the pathogenesis of PD, the molecular mechanisms underlying neuronal degeneration in PD remain unclear. Approximately 5% of PD cases have a clear familial etiology, showing classical recessive or dominant Mendelian modes of inheritance. PD-associated genes play important roles in cellular functions, such as lipid metabolism, membrane trafficking, mitochondrial functions, the ubiquitin-proteasomal system, and the autophagy-lysosomal pathway. In this review, we summarize recent progress in understanding the genetics of PD.
This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133+ and CD133- cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133+ cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133- cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133+ astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133- astrocytoma cells. So, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.
Deep brain stimulation (DBS) is a surgical procedure to treat motor symptoms in Parkinson disease (PD). DBS modulates neurological function of the target region using implanted medical devices to deliver electrical stimulation to the brain. The most common target for PD is the subthalamic nucleus (STN). STN DBS improves motor function in the medication-off state, motor fluctuations and dyskinesia with reduction of dopaminergic medication. Long-term outcomes are favorable for cardinal motor symptoms. However, refractory axial symptoms concerning speech, swallowing, gait and postural stability gradually deteriorated with progression of disease. New strategy to treat these axial symptoms is the future subject.
Background: Suicide is the leading cause of death of Japanese people aged 20-39 years. Improved stress-coping ability, here defined as sense of coherence (SOC), may reduce suicidal risk. The objective of the present study is to investigate the determinants of SOC, including age, in male Japanese workers.
Methods: Of the 467 employees of a nationwide company in Japan, 457 agreed to participate in this cross-sectional study. After exclusion of 43 females, the remaining 414 males were analyzed. SOC was measured by the SOC-13, and other data were collected using a self-administered questionnaire. Multiple linear regression analyses were performed to evaluate possible determinants of SOC.
Results: Higher age was significantly associated with increased SOC (β=0.14, p=0.014). Workers in their 40s and 50s had 2-3 points higher adjusted mean SOC scores than did workers aged 20-39 years. However, the most influential factor for SOC was sleep quality. Marital cohabitation status (living with a spouse) and drinking habits (current drinker) were also associated with higher SOC. In contrast, smoking habits, exercise habits, and night shift work were not significantly associated with SOC.
Conclusions: Our findings suggest that age, quality of sleep, drinking habits and marital cohabitation status may be mediators of SOC.
Objective: We aimed to elucidate changes in blood glucose and lipid metabolic parameters after high-carbohydrate diet ingestion in athletes with insulin resistance.
Methods: Ten throwers belonging to the university track and field club participated in this study. They underwent oral glucose tolerance test and high-carbohydrate test on 2 separate days with a 1-week interval. Serum insulin, lipid indices, and blood glucose levels were determined in both tests.
Result: According to the homeostasis model assessment for insulin resistance (HOMA-IR) score, three participants with HOMA-IR ≥2.5 were assigned to the high-HOMA-IR group and the remaining seven to the low-HOMA-IR group. The high-HOMA-IR group showed higher insulin and triglyceride levels after consuming the high-carbohydrate diet. Significant correlations were found between insulin and triglyceride levels and between HOMA-IR score and triglyceride levels after 180 min of a high-carbohydrate diet ingestion (r=0.80, and r=0.70, respectively).
Conclusion: The results of this study suggest that a high-carbohydrate diet results in high insulin levels in athletes with insulin resistance, which could lead to a state of high triglyceride levels.
In recent years, close attention has been paid to the role of glycocalyx, a structural component of the vascular endothelium that is made up of glycoproteins, proteoglycans, sugar chains, etc. Glycocalyx has been shown to have diverse functions, including suppression of blood coagulation within the vascular lumen, as well as regulation of platelet/neutrophil adhesion to the vascular lumen, regulation of the vascular permeability, sensing of mechanical stimuli such as shear stress, etc. For technical and other reasons, few advances have been made in research on glycocalyx, which has quite delicate and fragile features. However, with the recent progress in testing methods, research on glycocalyx has entered a new phase. Now, glycocalyx is known to play important roles not only in the pathogenesis of acute diseases (e.g., sepsis and post-ischemic reperfusion disorders), but also in the pathogenesis of chronic diseases such as diabetes mellitus and atherosclerosis. In this paper, we present the latest findings on the structure and functions of glycocalyx and their relationships to illnesses, etc.
A 38-year-old woman had hit the right front of her head in a traffic accident six years earlier, suffered a scalp hematoma, and an induration had remained at the point of contact. Six years later, the induration suddenly started to swell and pulsate, so she came to the hospital. When she visited the hospital, the mass was 3 cm×3.5 cm, pink on the surface, hard, and the ulsation disappeared when we pressed the superficial temporal artery(STA) anterior to the right external auditorymeatus. Three-dimensional (3D) computed tomography(CT) angiographydid not clearlyshow ontinuitybetween the mass and the STA, but we suspected a traumatic STA aneurysm and operated on her. Intraoperative findings showed that the mass was not an aneurysm and that, although it did not have direct continuity with the main trunk of the STA, the mass was accompanied by numerous blood vessels seeminglybranching from STA branches. Pathological findings ndicated the proliferation of small vessels with endothelial cells called epithelioid endothelial cells and the infiltration of eosinocytes and lymphocytes around the vessels, and led us to a diagnosis of angiolymphoid hyperplasia with eosinophilia (ALHE). Although the athogenesis of this disease remains unknown, past studies suggested that one cause might be damage to blood vessels bya trauma. We suggest that ALHE, rare as it is, should be onsidered in the differential diagnosis of a pulsatile scalp mass occurring after a head injury.