Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to increase intracellular Ca2+ concentrations ([Ca2+]i) and catecholamine release in adrenal chromaffin cells. We measured [Ca2+]i with fura-2 and recorded ion currents and membrane potentials with the whole cell configuration of the patch-clamp technique to elucidate the mechanism of PACAP-induced [Ca2+]i increase in bovine adrenal chromaffin cells. PACAP caused [Ca2+]i to increase due to Ca2+ release and Ca2+ influx, and this was accompanied by membrane depolarization and inward currents. The Ca2+ release was suppressed by ryanodine, an inhibitor of caffeine-sensitive Ca2+ stores, but was unaffected by cinnarizine, an inhibitor of inositol trisphosphate-induced Ca2+ release. Ca2+ influx and inward currents were both inhibited by replacement of extracellular Na+, and Ca2+ influx was inhibited by nicardipine, an L-type Ca2+ channel blocker, or by staurosporine, a protein kinase C (PKC) inhibitor, but was unaffected by a combination of omega- conotoxin-GVIA, omega-agatoxin-IVA, and omega-conotoxin- MVIIC, blockers of N-, P-, and Q-type Ca2+ channels. Moreover, 1-oleoyl-2-acetyl-sn-glycerol, a PKC activator, induced inward currents and Ca2+ influx. These results indicate that PACAP causes both Ca2+ release, mainly from caffeine-sensitive Ca2+ stores, and Ca2+ influx via L-type Ca2+ channels activated by membrane depolarization that depends on PKC-mediated Na+ influx.

Abstract:IgA vasculitis (IgAV) commonly occurs in young children, who present with a tetrad of purpura, abdominal pain, arthralgia and nephritis. Diffuse alveolar hemorrhage (DAH) is a rare complication of IgAV. We herein report an adult case of IgAV with a presentation of DAH and nephritis (pulmonary renal syndrome, PRS), but without other typical manifestations, such as purpura, abdominal pain and arthralgia. A 33-year-old man presented with hemoptysis and a low-grade fever and was diagnosed to have IgAV based on the results of a renal biopsy. Treatment with corticosteroids, cyclophosphamide, and plasmapheresis was effective. IgAV should therefore be considered in the differential diagnosis of adult PRS.

BackgroundWe sometimes experience the cases with fever and muscle pain of lower limbs without any other specific features. There are sporadic case reports of eosinophilic fasciitis and limb restricted vasculitis. However, few reports compare and discuss such cases.ObjectivesTo describe the clinical features, MRI findings, histopathology, diagnosis and response to treatment of these cases.MethodsWe retrospectively analyzed the clinical features of 28 patients who were admitted to our hospital because of fever and muscle pain of lower limbs from 2004 to 2016.ResultsAmong the 28 patients, 17 were vasculitis syndrome; eleven were limb restricted small vessel vasculitis (LrSvv), six were microscopic polyangiitis (MPA). Seven were fasciitis; three were eosinophilic fasciitis, three were diffuse fasciitis without eosinophilia and one was tuberculous fasciitis. One was relapsing polychondritis, one was Behçet's disease and the other two were myalgia without specific diagnosis. In our study, average age was 57.5±19.9 years old and older than in previously reported cases of limb ristricted vasculitis1,2. Sixteen were female, twelve were male. Abnormal MRI findings in non-infectious fasciitis and vasculitis syndrome were bilateral. Tuberculous fasciitis showed specifically abnormal intensity and fluid collection in unilateral thigh. Unilateral lesion and fluid collection may indicate infectious disease and bilateral lesion may indicate autoimmune or autoinflammatory diseases. MRI of vasculitis syndrome and fasciitis showed hyperintense T2-weighted signals in muscles of either legs, or thighs, or both. (n=3), MPA (n=1) and fasciitis (n=3). On MRI scan, abnormal fascial signal intensity was seen in all the patients with fasciitis and 6 (40%) with vasculitis syndrome. It was difficult to differentiate between vasculitis and fasciitis by MRI findings. Muscle biopsy was performed in 25 patients. In most cases, we performed en bloc biopsy, including muscle, fascia, skin and subcutaneous tissue. MRI was useful to determine the location of biopsy. All patients were treated with glucocorticoids. Immunosuppressive agents (azathioprine, n=10; methotrexate, n=5; cyclophosphamide, n=1; tacrolimus, n=1) were added in 15 patients and anti-tuberculous drugs in one. None of the 11 patients with LrSvv showed positive blood tests of anti-neutrophil cytoplasmic antibody or developed any other organ involvement during follow-up period (median 96 months; range 3–125). They responded well to glucocorticoid therapy (oral prednisolone 0.5–0.6mg/kg/day or intravenous methylprednisolone at doses of 1g/day). Recurrence rate of LrSvv patients was 0%, although that of MPA patients was 50% (n=3). In four patients with LrSvv, treatment was ceased and they achieved drug-free remission. There were no apparent differences between the patients who achieved drug-free remission and who didn't.ConclusionsMRI and muscle biopsy were useful for diagnosis of disease with fever and muscle pain of lower limbs.References Gallien S, et al. Ann Rheum Dis 2002;61:1107–9.Kh...

BackgroundPolymyositis/dermatomyositis (PM/DM) is a chronic autoimmune disease that is often complicated by interstitial lung disease (ILD). Anti-aminoacyl-transfer RNA synthetase antibody (ARS-Ab) and anti-melanoma differentiation-associated gene 5 antibody (MDA5-Ab) are highly detected in PM/DM with ILD. It was reported that ARS-Ab-positive-ILD (ARS-ILD) is often recurrent1, and patients with MDA5-Ab-positive-ILD (MDA5-ILD) develop fatal rapidly progressive ILD2.ObjectivesTo evaluate the differences in clinical courses between ARS-ILD and MDA5-ILD, including the changes in serum ILD markers.MethodsWe retrospectively investigated 25 patients with ARS-ILD and 26 patients with MDA5-ILD who received induction therapy between April 2002 and September 2017 at Kobe University Hospital. The survival rate and relapse-free survival rate were analysed with Kaplan-Meier estimation and the log-rank test. The differences in serum ILD markers between patients with ARS-ILD and MDA5-ILD were evaluated with the Student’s t-test.ResultsDisease subtypes at diagnosis with PM/DM-associated ILD were as follows: Eleven ARS-ILD and no MDA5-ILD patients had PM, 10 ARS-ILD and 5 MDA5-ILD patients had DM, and 4 ARS and 21 MDA5 patients had amyopathic DM. The survival rate for MDA5-ILD was significantly lower than that for ARS-ILD (p<0.01, figure 1A). On the other hand, there was no significant difference in the relapse-free survival rate between ARS-ILD and MDA5-ILD (p=0.25, figure 1B). The serum level of Krebs von den Lungen-6 was not significantly different between ARS-ILD and MDA5-ILD (1044.3±768.1 U/ml in ARS-ILD vs 1044. 863.1 ±566.5 U/ml in MDA5-ILD, p=0.33), but the serum level of ferritin was significantly higher in MDA5-ILD than in ARS-ILD (286.4±422.3 ng/ml in ARS-ILD vs 696.2±839.5 ng/ml in MDA5-ILD, p=0.04). Although the serum level of surfactant protein D (SP-D) in ARS-ILD was high, the SP-D level in MDA5-ILD was normal (158.9±82.1 ng/ml in ARS-ILD vs 46.3±22.1 ng/ml, p<0.01).ConclusionsMDA5-ILD patients should monitored for both rapidly progressive disease and relapsing disease. A normal SP-D level is a feature of MDA5-ILD.References[1] Nakazawa M, Kaneko Y, Takeuchi T. Risk factors for the recurrence of interstitial lung disease in patients with polymyositis and dermatomyositis: a retrospective cohort study. Clin Rheumatol2017. Epub ahead of print.[2] Hozumi H, Fujisawa T, Nakashima R, et al. Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease. Respir Med2016;121:91–9.Acknowledgementsnone.Disclosure of InterestNone declared

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