Alteration of regional cerebral blood flow to thyrotropin-releasing hormone therapy in acute encephalitis and encephalopathy during childhood.

BACKGROUND: Thyrotropin-releasing hormone (TRH) is now used as a therapeutic agent for various neurological disorders. Animal study has shown that TRH was attributable to increased cerebral blood flow (CBF). AIMS: There have been occasional reports that TRH therapy was effective for improving symptoms of persistent disturbance of consciousness after acute encephalitis or encephalopathy during childhood. To determine whether TRH has an effect on increasing CBF to patients who have consciousness disturbance caused by acute encephalitis or encephalopathy, and to determine the optimal method of administration. METHODS: Sixteen patients aged 0.7-10.9 years (mean age, 3.2+/-3.1 years) who presented with persistent disturbance of consciousness resulting from acute encephalitis or encephalopathy and were treated with TRH. Regional CBF (rCBF) was measured by single photon emission computed tomography before and after TRH therapy. The alteration rates of rCBF were compared between the divided two groups concerning the dose levels, dosing periods, and treatment lags. RESULTS: The alteration rates of rCBF of the high dose group were higher than those of the low dose group. Differences in the dosing periods and treatment lags did not cause any significant difference of the alteration rates of rCBF. CONCLUSION: The study showed that higher alteration rates of the CBF were observed in the higher dosing group, and TRH have the potency of increasing CBF. TRH therapy would have the potential for effective treatment of persistent consciousness disturbance caused by childhood acute encephalitis or encephalopathy.     

Chronological observation of surgically‐treated granuloma faciale implies the necessity of circumspect management for perinasal nodular subset

Granuloma faciale (GF) is a rare chronic dermatosis with still unknown etiopathology, which usually presents a solitary, asymptomatic, smooth reddish‐brown to violaceous plaques or nodules on the face. Various therapeutic approaches, including topical application of corticosteroid or tacrolimus and removal with laser, cryotherapy and surgery have been attempted; however, the outcome has been inconsistent. Herein, we report a case of perinasal nodular GF who repeatedly underwent surgical excisions after the failure of laser treatment. Despite its nomenclature, GF does not manifest granulomatous tissue and the lesion is histopathologically characterized by dense dermal cell infiltration devoid of granulomatous changes and not distinguished by a clear border, which partially explains the difficulty of complete removal in our case. Review of the published work delineated that GF could be largely divided into two clinical subsets: plaque and nodular types. The plaque type GF could be responsive to topical tacrolimus, an approach preferentially adopted nowadays, while nodular type GF was often resistant to topical therapies and required surgical or laser removal. The latter subset often arose around the nose. For this location, surgical excision with sufficient removal margin is sometimes technically difficult when an aesthetically acceptable outcome is expected, explaining the basis for local recurrence. Postoperative recurrence could be observed after years of disease‐free period. These observations indicated that the need for respective treatment strategies for the management of distinctive GF subsets. Of note, a multidisciplinary approach combining radical resection and additional supportive intervention with long‐term follow up may be required for perinasal and nodular GF.     

Immunomodulation of dendritic cells differentiated in the presence of nicotine with lipopolysaccharide from Porphyromonas gingivalis

Tobacco smoking is a significant risk factor for periodontal diseases. Nicotine, one of the most studied constituents in cigarette smoke, is thought to modify immune responses. Dendritic cells (DCs), which are key mediators between innate and adaptive immunity, stimulate naive T cells to differentiate to effector T‐cell subsets that may be actively involved in the immunopathogenesis of periodontal diseases. In this study, we evaluated the effects of nicotine and lipopolysaccharide (LPS) from Porphyromonas gingivalis, alone and in combination, on the functions of human monocyte‐derived DCs to elucidate the mechanism of tissue destruction of smoking‐associated periodontal diseases. P. gingivalis LPS‐stimulated DCs differentiated with nicotine (NiDCs) induced lower T‐cell proliferation and human leukocyte antigen (HLA)‐DR expression, but elevated expression of programmed cell death ligand 1. Additionally, NiDCs impaired interferon‐γ production but maintained interleukin (IL)‐5 and IL‐10 production in co‐cultured T cells. Furthermore, NiDCs produced lower levels of proinflammatory cytokines compared with DCs differentiated in the absence of nicotine. Interestingly, NiDCs preferentially produced the T helper 2 (Th2)‐type chemokines macrophage chemotactic protein‐1 and macrophage‐derived chemokine. These results suggest that the presence of nicotine during differentiation of DCs modulates the immunoregulatory functions of P. gingivalis LPS‐stimulated DCs.     

Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix

The lateral habenula (LHb) attracts a growing interest as a regulator of monoaminergic activity which were frequently reported to be defective in depression. Here we found that chronic social defeat stress (CSDS) increased production of pro-inflammatory cytokines in LHb associated with mobilization of monocytes and remodeling of extracellular matrix by increased matrix metalloproteinase (MMP) activity. RNA-seq analysis identified proprotein convertase Pcsk5 as an upstream regulator of MMP activation, with upregulation in LHb neurons of mice with susceptibility to CSDS. PCSK5 facilitated motility of microglia in vitro by converting inactive pro-MMP14 and pro-MMP2 to their active forms, highlighting its role in mobilization of microglia and monocytes in neuroinflammation. Suppression of Pcsk5 expression via small interfering RNA (siRNA) ameliorated depressive-like behaviors and pathological mobilization of monocytes in mice with susceptibility to CSDS. PCSK5-MMPs signaling pathway could be a target for development of the antidepressants targeting the inflammatory response in specific brain regions implicated in depression.Subject terms: Cellular neuroscience, Gene expression analysis     

Elucidation of demographic,clinical and trichoscopic features for early diagnosis of self-healing acute diffuse and total alopecia

The term “acute diffuse and total alopecia” (ADTA) has been often used as a synonym for self-regressing severe alopecia areata (AA). However, ADTA is originally defined as a rapidly-progressive subtype of AA (RP-AA) with short recovery time and favorable prognosis irrespective of interventions. Indeed, a subpopulation of ADTA recovers spontaneously. We focused on this unique subset of AA, which we coined as “self-healing ADTA” (sADTA). Prompt and accurate differentiation of sADTA from other RP-AA is important to avoid unnecessary treatments, which is still challenging due to the lack of predictive diagnostic hallmarks. In this study, 18 sADTA patients were retrospectively analyzed to delineate their demographics and clinical features, including gentle hair pull test and trichoscopic findings, followed by statistical comparison with those of RP-AA. All sADTA cases were female and the average age was 38.1 ± 15.9 years. The progression of hair loss areas peaked at 3.6 ± 1.5 months, and complete hair regrowth was achieved in 7.9 ± 1.7 months. The identified factors supporting the diagnosis of sADTA included being female; the absence of scalp pain and itch; the absence of extra-scalp hair loss; club hair predominance in hair pull test; predominant short vellus hairs; and increase in vacant follicular ostia on trichoscopy. Subsequently, a scoring system for early diagnosis of sADTA was developed by counting the number of six identified factors present in a tested case. When analyzed by the developed system, all sADTA cases, including an additional four cases, had scores of 4 or above, while all RP-AA cases had scores below 3 except one case. Therefore, the system successfully differentiated sADTA from RP-AA (P < 0.01). Despite some technical limitations, the current study suggested that sADTA is a distinctive entity with unique pathophysiology and that early diagnosis before intervention is feasible based on the characteristics.