Human skin functions not only as a barrier to retain the internal components and to protect internal organs from external stimulation or invasion, but also as a sensory organ to maintain homeostasis. In addition, it plays important roles in processes such as thermoregulation, antibody formation, vitamin D formation, lipid secretion, respiration, pigmentation and perception. [1][2][3][4][5][6] Stress disturbs the homeostasis, and may induce various disorders. For example, various kinds of physiological and psychological stress influence the hypothalamic-pituitaryadrenocortical axis, the hypothalamic-pituitary-gonadal axis, sympatho-adrenomedullary system and sympathetic nervous system, leading to changes in a number of organs. Stress has been implicated in hypertension, arteriosclerosis, diabetes mellitus, and other diseases in clinical and epidemiological studies.7) Skin function should also be influenced by stress, because it is primarily regulated by the autonomic nervous system and the endocrine system. This idea is supported by clinical reports showing that some skin disorders, including psoriasis and atopic dermatitis, are exacerbated by anxiety. 8)In addition, recent cutaneous biological studies have revealed that immobilization stress and/or overcrowding stress induced a decrease in lipogenesis in sebaceous glands, delay of skin barrier recovery and disruption of the skin barrier in rats, Syrian hamsters, and/or BALB/c mice.9-11) Barrier function and water retention are important cutaneous functions to maintain homeostasis. However, the relationship between stressful stimuli and skin dysfunction has not been established yet.Psychological stress activates the sympathetic nervous system, resulting in increases in the levels of glucocorticoids, catecholamines and angiotensin II in the circulating blood. Excess of glucocorticoid and angiotensin II can elevate blood pressure and excess of catecholamine increases cardiac output and peripheral resistance. Thus, stress induces acute hypertonic and chronic circulatory disorders. Hypertension causes hematogeneous disorder in the microvasculature. Therefore, concomitant reduced blood supply may contribute to peripheral ischemia. It is also suggested that mental stress induces transient endothelial dysfunction in humans. 12) Indeed, it is well recognized that psychological stress elevates blood pressure and that long-term stress causes dysfunction of the skin and various organs, such as ovary, kidney, thymus and adrenal glands.Recently, the laser Doppler perfusion-imaging technique has made it possible to map accurately changes of blood perfusion over a large area with good time resolution, and this method has been used to measure microcirculatory changes of the skin, mucosa, kidney and eye. 13,14) It has also been used for detecting abnormal blood flow in pathologically changed skin. 15)In this study, we have examined the relationship between blood perfusion and skin dysfunction mediated by catecholamines in animals exposed to a crowded environment. This approach ha...

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Although many drug treatments have been reported to theoretically improve semen parameters in male infertility, a standard method has not been established. The authors examined whether tranilast, a mast cell blocker, improves fertility and/or semen parameters in severe oligozoospermia. Seventeen patients with a sperm density of less than 10 x 10(6) sperm/mL and their fertile partners were enrolled in this study. Patients were prescribed tranilast 300 mg/day for at least 12 weeks. Semen and blood samples were collected before and after the prescription of tranilast for 12 weeks. Semen parameters, serum gonadotropins, luteinizing hormone, follicle-stimulating hormone, serum testosterone, and testicular size were evaluated. One patient complained of mild drowsiness during treatment. The sperm count was significantly increased after administration of tranilast in 7 patients (41.1%), although sperm motility was not altered. Semen volume and normal morphology were also unaltered. Three pregnancies were achieved. Endocrine profile and testicular size were unchanged. Tranilast, a mast cell blocker, is clinically useful for the treatment of severe idiopathic oligozoospermic men.

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ONO-2952, a novel antagonist of translocator protein 18 kDa (TSPO), binds with high affinity to TSPO in rat brain and human tumor cell line membrane preparations. This study used the TSPO-specific PET radioligand [ C]PBR28 to confirm binding of ONO-2952 to brain TSPO in human subjects, and evaluate brain TSPO occupancy and its relationship with ONO-2952 plasma concentration. Sixteen healthy subjects received a single oral dose of 200, 60, 20, or 6 mg ONO-2952 (n = 4 per dose). Two PET scans with [ C]PBR28 were conducted ≤7 days apart: at baseline and 24 h after ONO-2952 administration. [ C]PBR28 regional distribution volume (V ) was derived with kinetic modeling using the arterial input function and a two tissue compartment model. Nonspecific binding (V ) was obtained on an individual basis for each subject using linear regression as the x-intercept of the Lassen plot. The binding potential relative to V (BP ) was derived as the difference between V in the ROI (V ROI) and V , normalized to V ; BP = (V ROI - V )/V . TSPO occupancy was calculated as the change in BP (ΔBP ) from individual's baseline scan to the on-medication scan to the baseline BP value. TSPO occupancy by ONO-2952 was dose dependent between 20-200 mg, approaching saturation at 200 mg both in the whole brain and in 15 anatomic regions of interest (ROI). Estimated K values ranged from 24.1 to 72.2 nM. This open-label, single-center, single-dose study demonstrated engagement of ONO-2952 to brain TSPO. The relationship between pharmacokinetics and TSPO occupancy observed in this study support the hypothesis that ONO-2952 could potentially modulate neurosteroid production by binding to brain TSPO.