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Background: Ropivacaine is a long-acting local anesthetic with low cardiac toxicity that induces vasoconstriction in vitro and in vivo. Vascular smooth muscle tone is regulated by changes in both intracellular Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity. Therefore, the aim of this study was to examine the mechanism underlying the increase in [Ca2+]i in ropivacaine-induced vascular contraction. Methods: Ropivacaine-induced contractile responses and changes in [Ca2+]i were examined using an isometric force transducer and a fluorometer, respectively. Results: Ropivacaine induced a biphasic, concentration-dependent change in [Ca2+]i and contractile response in rat aortic smooth muscles: an increase in [Ca2+]i occurred at lower ropivacaine concentrations (3 × 10−5 to 3 × 10−4 M) and a decrease was observed at higher concentrations (10−3 to 3 × 10−3 M). Contraction and the [Ca2+]i increase induced by ropivacaine were attenuated significantly by a voltage-dependent Ca2+ channel antagonist, an inositol 1,4,5-triphosphate receptor antagonist and Ca2+-free solution ( P < 0.01, n = 6). Conclusion: Ropivacaine-induced contraction of rat aortic smooth muscle is, in part, regulated by Ca2+ influx from the extracellular space and Ca2+ release from the sarcoplasmic reticulum. [ABSTRACT FROM AUTHOR]

Background: Propofol induces dose-dependent vasodilation and hypotension in the clinical situation, and protein kinase C (PKC)-mediated Ca2+ sensitization plays an important role in vascular smooth muscle contraction. This study is designed to examine the effects of propofol on the active phorbol ester (phorbol 12, 13-dibutyrate; PDBu)-induced, PKC-mediated contraction of rat aortic smooth muscle. Methods: The PDBu-induced contraction of endothelium-denuded rat aortic rings was measured in the presence or absence of PKC inhibitor, bisindolylmaleimide I, or propofol, using isometric force transducers. The PDBu-induced PKC phosphorylation of endothelium-denuded rat aortic strips was detected in the presence or absence of bisindolylmaleimide I or propofol, using Western blotting. Results: PDBu, but not the inactive phorbol ester, 4-α-phorbol 12-myristate-13-acetate, dose-dependently induced both a slowly developing sustained contraction and PKC phosphorylation of rat aortic smooth muscle, reaching the peak level at the concentration of 10−6 M. The PDBu (10−6 M)-induced contraction was dose-dependently inhibited by bisindolylmaleimide I with reductions of 6.8 ± 1.8% ( P > 0.05), 39.8 ± 8.7% ( P < 0.01) and 96.7 ± 1.4% ( P < 0.01) in response to concentrations of 5 × 10−7 M, 10−6× M and 5 × 10−6 M, respectively, and by propofol with decreases of 5.2 ± 1. 6% ( P > 0.05), 9.4 ± 1.7% ( P < 0.05), 65.3 ± 9.2% ( P < 0.01) and 96.2 ± 1.6% ( P < 0.01) in response to concentrations of 5 × 10−7 M, 10−6 M, 5 × 10−6 M and 10−5 M, respectively. Both bisindolylmaleimide I and propofol also inhibited the PDBu-induced increase in the density of the phosphorylated PKC bands in a dose-dependent manner, with decreases of 6.3 ± 2.8% ( P > 0.05), 42.9 ± 3.2% ( P < 0.01) and 96.6 ± 3.4% ( P < 0.01) in response to 5 × 10−7 M, 10−6 M or 5 × 10−6 M bisindolylmaleimide I, respectively, and with decreases of 4.2 ± 2.5% ( P > 0.05), 13.5 ± 1.7% ( P < 0.05), 69.5 ± 3.5% ( P < 0.01) and 95.3 ± 4.3% ( P < 0.01) in response to 5 × 10−7 M, 10−6 M, 5 × 10−6 M and 10−5 M propofol, respectively. Conclusion: Propofol dose-dependently inhibits PDBu-induced, PKC-mediated contraction of rat aortic smooth muscle. [ABSTRACT FROM AUTHOR]

Isoflurane induces greater effects on vasodilation and decreasing blood pressure than sevoflurane. Tyrosine kinase-catalyzed protein tyrosine phosphorylation plays an important role in regulating vascular smooth muscle contraction. The aim of the present study was to compare the effects of isoflurane and sevoflurane on tyrosine phosphorylation-mediated vascular constriction, by assessing the degree of sodium orthovanadate (Na3VO4, tyrosine phosphatase inhibitor)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle. Na3VO4-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle were measured in the presence of genistein, a tyrosine kinase inhibitor, and different concentrations of isoflurane and sevoflurane, using isometric force measurement and Western blot, respectively. Na3VO4 (10−4 M) induced sustained contraction and tyrosine phosphorylation of substrates that were both markedly attenuated in the presence of genistein (5 × 10−5 M). Isoflurane and sevoflurane dose-dependently (1, 2, 3 MAC) attenuated the Na3VO4-induced contraction ( P < 0.05–0.005, n = 8), with a greater degree of inhibition by isoflurane than sevoflurane at 2 MAC ( P < 0.01) and 3 MAC ( P < 0.05). Both anesthetics also attenuated the total band density of the Na3VO4-induced, tyrosine-phosphorylated substrates in a concentration-dependent manner ( P < 0.05–0.005, n = 4), with much greater attenuation by isoflurane than sevoflurane at 1 and 2 MAC ( P < 0.05), respectively. The results of the present study demonstrate that isoflurane exhibits a greater degree of inhibition on the Na3VO4-stimulated contraction and protein tyrosine phosphorylation of rat aortic smooth muscle compared with sevoflurane. These findings suggest that isoflurane depresses the protein tyrosine phosphorylation-mediated contraction of vascular smooth muscle to a greater degree than sevoflurane. [ABSTRACT FROM AUTHOR]

We present a novel microscopic model of sorption and convection of ions in heterogeneous media. Our model is based on an analogy to electron transport in a semiconductor. A new feature of our model is a power law random distribution of the adsorption time of ions. Diverging standard deviation of the distribution function yields anomalous ion transport. We show that this anomalous transport explains a concentration profile with a long tail that has been observed in column experiments. We successfully fit recent experimental data. Finally, we propose new experiments by which we can check the validity of our model. [ABSTRACT FROM AUTHOR]

Prurigo chronica multiformis is a commonly used diagnostic designation for a peculiar subtype of prurigo in Japan, although the disease entity might not be well-recognized in other countries. Experts approved by the Japanese Dermatological Association attempted to build a common consensus on prurigo chronica multiformis, agreeing that it is a unique and important disease entity in elderly patients. Skin lesions are characterized by intensely pruritic, edematous, urticarial papules, or small macules, which gradually become solid papules/small nodules. The papules tend to aggregate and occasionally coalesce into polygonal lichenified plaques. The most commonly affected sites are the lower abdomen and lower back, although the chest, thighs, and upper back might also be involved. Common histopathological features of prurigo chronica multiformis include infiltration of lymphocytes and eosinophils in the upper dermis, with minimal epidermal changes. Basophil infiltration is also observed. The epidemiological incidence, differences in clinical manifestations by geographical location, and disease placement among other forms of prurigo and/or related skin diseases need to be further elucidated. Dermatologists should be aware of the clinical characteristics of prurigo chronica multiformis., (© 2024 Japanese Dermatological Association.)

A Japanese male in his 30s with no underlying medical condition presented with painless nodules after being bitten by a dog during a stay in Bali, Indonesia, 7 years earlier. He was referred to our department with multiple ulcers, nodules, and masses on the right leg. The final diagnosis was mycetoma caused by Nocardia vulneris, which may have been exacerbated by colonization of Candida parapsilosis and C. tropicalis as these yeasts were isolated by culture from the tissue. Treatment with minocycline hydrochloride and sulfamethoxazole trimethoprim showed partial efficacy, but the addition of posaconazole achieved significant efficacy. This suggests that the surmised coexistence of pathogenic yeasts of lower virulency may have made mycetoma in this case intractable., (© 2024 Japanese Dermatological Association.)

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis., (© 2023 Japanese Dermatological Association.)

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA., (© 2023 Japanese Dermatological Association.)

Background Sex difference in fractional flow reserve (FFR) and resting index has not been fully clarified. We sought to investigate the impact of sex on the discordance of revascularization decision making between FFR and diastolic pressure ratio during the diastolic wave-free period (dPR WFP ). Methods and Results A total of 759 angiographically intermediate lesions with 30% to 80% diameter stenosis by quantitative coronary angiography in 577 patients in whom FFR and dPR WFP were measured were investigated. dPR WFP was measured during the wave-free window of 5 heart cycles at an independent core laboratory. FFR ≤0.80 and dPR WFP ≤0.89 were considered positive studies. A total of 164 vessels in 126 women (21.6%) and 595 vessels in 451 men (78.4%) were included. In lesions with negative dPR WFP , positive FFR was less frequently observed in women (13 of 73; 17.8%) than in men (97 of 286; 33.9%) ( P =0.009). In lesions with positive dPR WFP , the frequency of negative FFR was observed in 22 of 91 vessels (24.2%) in women and 51 of 309 vessels (16.5%) in men, which did not reach statistical significance ( P =0.098). In multivariable analyses, female sex was independently associated with FFR-dPR WFP discordance both in negative dPR WFP cohort (odds ratio, 0.44; 95% CI, 0.21-0.98; P =0.036) and in positive dPR WFP cohort (odds ratio, 2.41; 95% CI, 1.17-4.96; P =0.017) after adjustment for age, weight, quantitative coronary angiography data, and baseline physiological indexes. Conclusions The frequency of FFR-dPR WFP discordance was significantly associated with sex, which may indicate potential shift of optimal threshold of either FFR or dPR WFP , or both of them, according to sex.

A case of severe fever with thrombocytopenia syndrome (SFTS) in which a skin biopsy from the tick-bite region was analyzed is reported. The patient was a 72-year-old woman who developed fever and thrombocytopenia after a tick bite. SFTS was diagnosed from polymerase chain reaction (PCR) analysis of a blood sample. Histopathological analysis of a skin biopsy specimen from the tick-bite region showed CD20-positive perivascular and interstitial immunoblastic cells, which were positive to anti-SFTS virus (SFTSV) nucleoprotein antibody. In addition, SFTSV RNA was detected by real-time PCR from this biopsy specimen. Moreover, hemophagocytosis was also found in the tick-bite region. To the best of our knowledge, this is the first report to analyze the details of the tick-bite region of skin in SFTS, and the first to detect virus-infected cells in the skin. The present findings may help elucidate the mechanisms of entry of SFTSV., (© 2019 Japanese Dermatological Association.)

Hereditary lactate dehydrogenase (LDH) M-subunit deficiency is very rare and we have found reports of close to a dozen cases in the published work, two of which were associated with pustular psoriasis-like lesions. We report a third case of pustular psoriasis-like eruptions associated with LDH M-subunit deficiency, which occurred 24 years after the diagnosis of LDH M-subunit deficiency. These cases indicate that abnormal activity of LDH can induce pustular psoriatic lesions in the long term. Some patients with symptoms of hereditary LDH M-subunit deficiency have antecedent annular scaly plaque lesions, that resemble psoriatic lesions. We discuss a hypothesis to explain this scenario., (© 2016 Japanese Dermatological Association.)

Pemetrexed, which is used for the treatment of non-small cell lung carcinoma and malignant mesothelioma, induces cutaneous adverse reactions in approximately 20% of patients. There are also reports of the induction of fibrosing disorders. We describe a case of pemetrexed-induced scleroderma-like conditions in the lower legs of a patient whose pulmonary carcinoma has been relatively well controlled, with prolongation of the dose interval, in spite of the discomfort in both his legs. Skin biopsy revealed dermal fibrosis and dilated lymph vessels in the dermis, but lymphocytic infiltration around the lymph vessels, in contrast to the blood vessels, was minimal. Immunohistochemical staining revealed that the major subsets of T cells that had infiltrated around blood vessels were CD3 and CD45Ro, but no B cells were detected. High serum levels of interleukin (IL)-4 and IL-6 suggested that T cells, which secrete these cytokines, may be involved in the pathogenesis of this condition. Magnetic resonance imaging of the lower extremities revealed muscular and fascial involvement. Several chemotherapeutic agents, such as taxanes, gemcitabine and bleomycin, are known to induce scleroderma-like changes, and we should also keep the side-effects of pemetrexed in mind when we encounter patients with fibrosing conditions., (© 2016 Japanese Dermatological Association.)

Pigmented cosmetic dermatitis-like (Riehl's melanosis-like) pigmentation was reported in three of 27 patients with primary Sjögren's syndrome. But case reports of such eruptions are rare. We describe three cases of such eruptions associated with primary Sjögren's syndrome or anti-SSA antibody and possible associations with specific types of human leukocyte antigen (HLA) and infiltrating lymphocytes. These middle-aged Japanese women had reticular facial pigmentation and histopathological examination revealed interface dermatitis, melanophages, and dense lymphocytic infiltration around hair follicles and sweat ducts. HLA typing revealed common antigenic equivalents or genetic typing of HLA-A2, DR52, DPA1(02:02) and DPB1(05:01). Immunohistochemical staining revealed major subsets of T cells to be CD8 and CD45RO. Some Foxp3- and few IL17-positive cells were found in strong contrast to the major CD4 subset of infiltrated T cells in annular erythema associated with Sjögren's syndrome. Apparently, our patients' pigmentation represented a specific etiology associated with primary Sjögren's syndrome or anti-SSA antibody., (© 2016 Japanese Dermatological Association.)

We performed skin cancer screenings for 2 or 3 days annually from 2006 through 2013 in Oita Prefecture, Japan. Screening of approximately 3000 people in total allowed us to identify and treat several skin cancers, including five cases of malignant melanoma, four of squamous cell carcinoma, 16 of basal cell carcinoma, 11 of Bowen's disease, 17 of actinic keratosis, one of extramammary Paget's disease and one of metastatic breast carcinoma. The sensitivity and specificity for the category defined by an identified lesion associated with risk of cancer and requiring further examination (category C) were 92.7% and 95%, respectively. We cannot estimate the outcome of our skin cancer screenings in terms of cancer mortality because of the small number of subjects examined and the brief follow-up period. However, we did estimate the effectiveness of these screenings in terms of stages or sizes of cancerous lesions. The relative numbers of subjects with malignant melanoma at various clinical stages, identified during skin cancer screenings and during a routine visit to our hospital, were significantly different. We also compared, statistically, the sizes of lesions in Bowen's disease that were found during cancer screenings and during a direct visit to our hospital. The former lesions were smaller than the latter. Our data suggest the benefits of our skin cancer screenings and the importance of campaigns and education to encourage people to visit dermatologists for the detection of skin cancers at an early stage., (© 2015 Japanese Dermatological Association.)

Elimination of epiplakin (EPPK) by gene targeting in mice results in acceleration of keratinocyte migration during wound healing, suggesting that epithelial cellular EPPK may be important for the regulation of cellular motility. To study the function of EPPK, we developed EPPK knock-down (KD) and EPPK-overexpressing HeLa cells and analyzed cellular phenotypes and motility by fluorescence/differential interference contrast time-lapse microscopy and immunolocalization of actin and vimentin. Cellular motility of EPPK-KD cells was significantly elevated, but that of EPPK-overexpressing cells was obviously depressed. Many spike-like projections were observed on EPPK-KD cells, with fewer such structures on overexpressing cells. By contrast, in EPPK-KD cells, expression of E-cadherin was unchanged but vimentin fibers were thinner and sparser than in controls, and they were more concentrated at the peri-nucleus, as observed in migrating keratinocytes at wound edges in EPPK(-/-) mice. In Matrigel 3-D cultures, EPPK co-localized on the outer surface of cell clusters with zonula occludens-1 (ZO-1), a marker of tight junctions. Our results suggest that EPPK is associated with the machinery for cellular motility and contributes to tissue architecture via the rearrangement of intermediate filaments., (© 2013 Japanese Dermatological Association.)