Hypohidrosis Plays a Crucial Role in the Vicious Circle of Bathing Suit Ichthyosis: A Case with Summer Exacerbation

Although percutaneous coronary intervention (PCI) is a highly effective modality for the management of acute coronary syndromes, it can potentiate the existing prothrombotic state around lesion areas and lead to ischaemic complications. Adjunctive pharmacologic treatment with heparin reduces the risk of ischaemic events, but the utility of heparin is limited by its unpredictable pharmacodynamic effects and its inability to modulate fibrin-bound thrombin. Additionally, a potential risk of heparin-induced thrombocytopenia is associated with heparin use. Direct thrombin inhibitors (DTIs) have emerged as potential alternatives to heparin in patients undergoing PCI. Bivalirudin is a DTI indicated for use in PCI. Results from various studies have suggested clinical benefit associated with the use of bivalirudin, driven primarily by the reduction in bleeding risks compared with the standard treatment regimens. Of concern, however, is a significant increase in acute stent thrombosis with bivalirudin monotherapy compared with heparin plus GPIIb/IIIa inhibitors following primary PCI for ST-segment elevation myocardial infarction (STEMI). Desirudin is a highly potent DTI with greater binding affinity than bivalirudin for thrombin. This report provides a comparative overview of the pharmacology and clinical utility of desirudin and bivalirudin in the setting of PCI

Mice lacking the<em> kf-1</em> gene exhibit increased anxiety- but not despair-like behavior

KF-1 was originally identified as a protein encoded by human gene with increased expression in the cerebral cortex of a patient with Alzheimer&rsquo;s disease. In mouse brain, kf-1 mRNA is detected predominantly in the hippocampus and cerebellum, and kf-1 gene expression is elevated also in the frontal cortex of rats after chronic antidepressant treatments. KF-1 mediates E2-dependent ubiquitination and may modulate cellular protein levels as an E3 ubiquitin ligase, though its target proteins are not yet identified. To elucidate the role of kf-1 in the central nervous system, we generated kf-1 knockout mice by gene targeting, using Cre-lox recombination. The resulting kf-1&minus;/&minus; mice were normal and healthy in appearance. Behavioral analyses revealed that kf-1&minus;/&minus; mice showed significantly increased anxiety-like behavior compared with kf-1+/+ littermates in the light/dark transition and elevated plus maze tests; however, no significant differences were observed in exploratory locomotion using the open field test or in behavioral despair using the forced swim and tail suspension tests. These observations suggest that KF-1 suppresses selectively anxiety under physiological conditions probably through modulating protein levels of its unknown target(s). Interestingly, kf-1&minus;/&minus; mice exhibited significantly increased prepulse inhibition, which is usually reduced in human schizophrenic patients. Thus, the kf-1&minus;/&minus; mice provide a novel animal model for elucidating molecular mechanisms of psychiatric diseases such as anxiety/depression, and may be useful for screening novel anxiolytic/antidepressant compounds

A Case of Old Age-Onset Generalized Pustular Psoriasis with a Deficiency of IL-36RN (DITRA) Treated by Granulocyte and Monocyte Apheresis

A 78-year-old woman who had been suffering from psoriasis vulgaris for 31 years was admitted to hospital because of her erythroderma. A toxic eruption was suspected and she was treated with prednisolone 30 mg daily. However, it was ineffective and, suspecting psoriatic erythroderma, cyclosporine 150 mg daily was administered with tapering of the prednisolone. Two weeks after a dose reduction of cyclosporine to 100 mg/day, erythroderma with widespread generalized pustules and fever developed. Histology of a biopsy revealed inflammatory infiltrates in the skin with a spongiform pustule of Kogoj, which was consistent with generalized pustular psoriasis (GPP). Her pustules improved with additional etretinate 20 mg/day, but the erythroderma persisted and she consulted us. Three sessions of granulocyte and monocyte apheresis once weekly were effective for her condition and decreased her serum levels of IL-6 and IL-8. She had homozygous mutations of c.[28C>T] in IL36RN which cause p.[Arg10Ter]. She is the oldest reported case of GPP with a deficiency of interleukin-36 receptor antagonist (DITRA), although GPP in DITRA has been suggested to usually occur in younger cases with no pre-existing psoriasis vulgaris

Serum Cytokines Correlated with The Disease Severity of Generalized Pustular Psoriasis

To characterize serum biomarkers reflecting the severity of generalized pustular psoriasis (GPP), we measured multiple cytokine/chemokine levels in 39 serum samples from 6 cases with GPP during the course of the disease. Serum levels of IL-4, IL-8, CXCL1 and CCL3 were positively correlated with the severity scores of GPP, white blood cell counts and serum C-reactive protein levels. Serum levels of IL-1β, IL-1ra, IL-6, IL-10, IL-12p70, IL-18, IL-22, IFN-γ and VEGF showed strong positive correlations (r > 0.4, p < 0.01) with all those 3 clinical markers. Of those, IL-10 and IL-22 were significantly decreased after treatment in parallel with the GPP score and therefore those two serum cytokines might be useful to evaluate the efficacy of treatment for GPP

Serum Procalcitonin and Presepsin Levels in Patients with Generalized Pustular Psoriasis

Patients with generalized pustular psoriasis (GPP) often present with symptoms that must be differentiated from sepsis. Procalcitonin (PCT) and presepsin (P-SEP) are widely used as biomarkers for sepsis; therefore, we examined the serum PCT and P-SEP levels in patients with psoriatic diseases. The enrolled patients included 27 with psoriasis vulgaris (PV) (22 males, 5 females; mean age 47.7 years), 12 with psoriatic arthritis (PsA) (8 males, 4 females; mean age 51.3 years), and 15 with GPP (10 males, 5 females; mean age 63.7 years). The mean serum PCT levels in patients with PV, PsA, and GPP were 0.01 ng/mL (25th–75th percentile; 0.00–0.03), 0.013 ng/mL (0.00–0.03), and 0.12 ng/mL (0.05–0.18), respectively; the levels of PCT were higher for patients with GPP than with PV or PsA but were lower than the PCT cutoff value (0.5 ng/mL) for the diagnosis of infection. The mean serum P-SEP levels in patients with PV, PsA, and GPP were 144.9 pg/mL (25th–75th percentile; 78–181), 168.1 pg/mL (124–203), and 479.9 pg/mL (216–581), respectively. Unexpectedly, the levels of P-SEP in the patients with GPP were as high as the P-SEP cutoff value (317 to 647 pg/mL) used for the diagnosis of infection. We also found that neutrophils produced P-SEP, suggesting that the high serum P-SEP levels in patients with GPP might arise at least in part due to the P-SEP derived from neutrophils activated in GPP. Both serum PCT and P-SEP might therefore be useful as novel serum biomarkers for GPP because their levels were decreased by GPP treatments. However, the measurement of PCT might be more useful than the measurement of P-SEP for discriminating between GPP and sepsis

Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with CERS3 mutations

The stratum corneum (SC) of the epidermis acts as a skin permeability barrier, and abnormalities in SC formation lead to several skin disorders. Lipids, especially the epidermis-specific ceramide classes omega-O-acylceramides (acylceramides) and protein-bound ceramides, are essential for skin barrier formation. Ceramide synthase 3 (CERS3) is involved in the synthesis of acylceramides and protein-bound ceramides, and CERS3 mutations cause autosomal recessive congenital ichthyosis. In the present study, we measured ceramide synthase activity and performed comprehensive SC ceramide profiling in an ichthyosis patient with compound heterozygous CERS3 mutations: nonsense mutation p.Arg75* and missense mutation p.Arg229His. The activity of p.Arg75* and p.Arg229His mutant CERS3 proteins was reduced to 4% and 56%, respectively, of the wild-type protein. In the patient's SC, acylceramide levels were greatly reduced, but the levels of protein-bound ceramides remained almost unchanged. Non-acylated ceramide levels were also affected in the patient; in particular, the levels of ceramides composed of sphingosine and non-hydroxy or alpha-hydroxy fatty acid were substantially higher than in healthy controls. These results suggest that a reduction in acylceramide levels alone leads to ichthyosis. Although protein-bound ceramides are synthesized from acylceramides, levels of acylceramides and protein-bound ceramides are not necessarily correlated