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Notes: Summary Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid fibrils on leptomeningeal and cortical blood vessels, and the incidence of this disorder increases with age. However, this form of vascular amyloid deposition rarely involves tissues outside of the brain. A 71-year-old woman first developed some deterioration in memory, and soon afterwards suffered from recurrent episodes of subcortical hemorrhage. Histopathological examination of this case revealed typical pathology of Alzheimer's disease with an extensive appearance of β-protein type CAA, and additionally, the spinal leptomeningeal vessels and the pia-arachnoid membranes were also affected by amyloid β-protein deposits. The spinal cord involvement associated with CAA and Alzheimer's disease is unusual, and the present case provides additional important information on the pathogenesis of disorders with β-protein deposition including Alzheimer's disease.

Notes: Summary Within the generalized equilibrium statistics recently introduced by Tsallis (p n ∝[1−β(q−-1) εn ]1/(q−)), we calculate the thermal dependence of the specific heat corresponding to a harmonic-oscillator-like spectrum, namely ε n ω(n−α) (∀ω〉0,n=0,1,2,...). The influences ofq and α are exhibited. Physically inaccessible and/or thermally frozen gaps are obtained in the low-temperature region, and, forq〉1, oscillations are observed in the high-temperature region. The specific heat of the two-level system is also shown.

Notes: After the initial discovery that, in vivo, mammalian skin both transcribes and translates the proopiomelanocortin (POMC) gene, and processes its product into melanocortins (Slominski et al., Experientia 1992), it has become increasingly appreciated that the hair follicle – including the human one – is a prime source and target not only of POMC-derived “pituitary” hormones, e.g. alpha-MSH, ACTH and ß-endorphin, but also expresses the most proximal control element of the hypothalamic-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and its receptor (e.g. Roloff et al. FASEB J 1998, Ito et al. J Invest Dermatol 2004). However, while all proximal elements of the HPA are expressed in both murine and human hair follicles (CRH, CHR-R, POMC, ACTH and ACTH-R), it has neither been shown that these are functionally linked (i.e., is CRH actually capable of modulating intrafollicular POMC gene expression and ACTH production?), nor has it been known whether the most distal HPA component – cortisol synthesis – is also present in the hair follicle. Therefore, we have investigated whether the stimulation of microdissected, organ-cultured human hair follicles with CRH or ACTH elicits responses inside this peripheral miniorgan that imitate a functional HPA – in the absence of any systemic or neural connections and under serum-free culture conditions. Here, we show that CRH stimulation of organ-cultured human scalp hair follicles in the anagen VI stage of the hair cycle indeed results in significant upregulation of POMC transcription, and of alpha-MSH, ACTH, MC1, MC2 and glucocorticoid receptor (GR) immunoreactivity in situ (immunofluorescence). ACTH stimulation, in turn, significantly up-regulates the – already constitutively present!– cortisol-immunoreactivity as well as cortisol secretion into the culture medium. This represents the first available evidence that normal human skin (more precisely: the hair follicle) can actually synthesize the “adrenal” steroid hormone cortisol in situ, and that this acticity is regulated by the same “hypothalamic” and “pituitary” hormones that operate as key controls of adrenal cortisol synthesis. Moreover, we show that cortisol stimulation exerts classical feedback responses inside the human anagen hair follicle recognized for the central HPA: cortisol up-regulates GR, while it down-regulates CRH expression. Given that the HPA operates as the major system for coordinating stress-responses of the mammalian organism and for integrating them into changing metabolic demands and neuro-endocrine-immune signaling circuits, it has fascinating implications (e.g. for general skin physiology and dermatological therapy), and raises most intriguing questions, that human hair follicles are utilizing a fully functional peripheral equivalent of the central HPA.

Notes: The hair follicle offers an exquisite model for the experimental exploration of key issues of cutaneous neuroimmunology, for example, how local, intracutaneous and systemic stress–response systems are integrated with the skin immune system and with epithelial–mesenchymal interactions (as they occur during hair follicle growth and cycling). Previously, we had shown that skin mast cells, which operate as central switchboards of inflammation and tissue remodelling, also are important regulators of hair growth in mice and that endogenous, immunomodulatory mast cell secretagogues are potent hair growth modulators. This is true both for secretagogues that are generated by the hair follicle epithelium itself (e.g. ACTH) and for mast cell-activating neuropeptides synthesized by the sensory hair follicle innervation (e.g. SP). Also, we had shown that the prototypic stress-associated neuropeptide, SP, plays a crucial role in mediating the hair growth-inhibitory, mast cell-activating, inflammation- and catagen-promoting properties of chronic psychoemotional stress on murine hair follicles. Now, we show that the immunomodulatory and mast cell-activating neurotrophin, NGF, is also crucially involved in mediating the inhibitory effects of stress on murine hair growth. Furthermore, the central, stress-related neurohormone CRH, a recognized mast cell secretagogue which is expressed by the hair follicle epithelium, also is a hair growth inhibitor and activates a fully functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis within organ-cultured human scalp hair follicles, including the synthesis and secretion of cortisol as well as the induction of classical feedback loops. We also demonstrate that one of the melanocortins whose intrafollicular synthesis is stimulated by CRH (α-MSH) is a potent suppressor of MHC class I expression in situ and is thus capable of restoring the collapsed immune privilege of human anagen hair bulbs, while SP upregulates the ectopic expression of MHC class I, thus endangering the hair follicle immune privilege. Finally, we show that vanilloids long exploited as experimental tools for neuroimmunological research in the skin (capsaicin) can, in fact, directly modulate human hair growth via the stimulation of vanilloid receptors (VR1) expressed by the follicle epithelium, in addition to stimulating vanilloid expressed by skin mast cells. Therefore, the hair follicle offers an ideal, highly instructive and clinically most relevant research model for dissecting how nervous system, central and peripheral (neuro-) endocrine signalling loops and the immune system interact in order to adapt skin functions to changing environmental conditions (e.g. in response to external stressors, by alterating, e.g. keratinocyte proliferation/apoptosis, skin immune status, as well as defined cutaneous metabolic and endocrine activities).

Notes: The pineal hormone, melatonin exerts many functional effects on mammalian skin (e.g. melanogenesis inhibition, melanocyte growth inhibition, and regulation of seasonal pelage hair growth). However, its cutaneous expression, regulation, and functional role are still obscure. The aim of this study was to check whether murine hair follicles are indeed direct, peripheral melatonin targets which express melatonin membrane receptors (MT1 and MT2) and orphan nuclear receptor α (RORα) which interact with melatonin. Immunohistochemistry revealed that murine hair follicle keratinocytes show both MT1-like immunoreactivity (IR) and ROR-like IR, both of which changed substantially in a hair cycle-dependent manner. Both semiquantitive RT-PCR for MT1 and MT2, and quantitive real-time PCR for MT1, MT2, and ROR on murine skin cDNA revealed that all three genes are transcribed in normal mouse skin in hair cycle-dependent manner. Functionally, melatonin significantly inhibited the constitutional level of epidermal and hair follicle keratinocyte apoptosis in short-term mouse skin organ culture. In conclusion, we here provide evidence that normal murine hair follicles are prominent direct target for melatonin bioregulation which express MT1, MT2, and ROR, at least some of which are functionally active in situ. These receptors are regulated in a hair cycle-dependent manner, suggesting a role of melatonin in hair cycle control.

Notes: Abstract The present study was carried out to investigate histologically and histometrically the effect of fluoride on root resorption induced by mechanical injuries of the periodontal soft tissues in rats. Resorption lacuna in the root surface of the molar in animals given both mechanical injuries and fluoride administration was significantly smaller in length and area than that in animals given only mechanical injuries. Moreover, resorption lacuna in the former animals contained fewer odontoclasts than that in the latter. The results of the present study might suggest that the administration of fluoride suppressed root resorption induced by mechanical injuries of the periodontal soft tissues.