Urticaria associated with hyper-IgE in a patient with psoriasis undergoing treatment with efalizumab.

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Novel perspectives in redox biology and pathophysiology of failing myocytes: modulation of the intramyocardial redox milieu for therapeutic interventions - A review article from the Working Group of Cardiac Cell Biology, Italian Society of Cardiology

The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, and economic costs, in spite of huge efforts in understanding pathogeneticmechanisms and in developing effective therapies that have transformed this syndrome into a chronic disease. Myocardial redox imbalance is a hallmark of this syndrome, since excessive reactive oxygen and nitrogen species can behave as signaling molecules in the pathogenesis of hypertrophy and heart failure, leading to dysregulation of cellular calcium handling, of the contractile machinery, of myocardial energetics and metabolism, and of extracellular matrix deposition. Recently, following new interesting advances in understanding myocardial ROS and RNS signaling pathways, new promising therapeutical approaches with antioxidant properties are being developed, keeping in mind that scavenging ROS and RNS tout court is detrimental as well, since these molecules also play a role in physiological myocardial homeostasis

Editorial: Fibrosis and inflammation in tissue pathophysiology

In adult mammals, tissue damage activates a wound healing response with acute inflammation followed by either complete repair (for low-grade damage or in highly regenerative tissues, such as the liver) or replacement fibrosis (for extensive damage or in poorly regenerative tissues, such as the myocardium). Persistent damage and repeated insults sustain continuous activation of repair pathways leading to chronic inflammation, progressive tissue fibrosis and sclerosis. Despite the evolutionary advantage conferred by scarring as a rapid repair mechanism, chronic fibrosis leads to tissue adverse remodeling and impaired function. Persistent low-level inflammation and fibrosis are observed in many pathological conditions (e.g. hypertension, obesity, diabetes, genetic diseases), and lead to further complications including atherosclerosis and ischemic events, organ failure, autoimmune diseases, cancer, aging, and reduced resilience to infectious diseases. Pathological fibrosis plays a major role in a wide range of diseases, accounting for an increasingly large fraction of mortality cases worldwide. While recent advances have unveiled many environmental and genetic causes of fibrotic disorders, a better understanding of both ubiquitous and tissue-specific regulatory pathways and cellular dynamics could help to design new targeted therapies, and to identify the etiology of idiopathic diseases. Within this Research Topic, we invite submission of articles (reviews, original research, or methodology articles) on the pathophysiological role of fibrosis and inflammation in different tissues. Areas to be covered include, but are not limited to: - genetic and environmental causes of persistent low-level inflammation and fibrosis (e.g. autoimmunity, hypertension, obesity, diabetes, genetic diseases, latent infections); - comorbidities including systemic sclerosis, neurological disorders, organ failure (heart, skeletal muscle, kidney, liver, lungs), cancer, and reduced resilience to infectious diseases; - in vivo (animal models) and in vitro (organoids, tissue culture) modelling of fibrotic diseases for the discovery of novel therapeutic targets and potential tissue-specific treatments; - vascular responses to inflammation and inflammation of vascular tissues; - system biology approaches to identify molecular and cellular networks leading to chronic inflammation and fibrosis

Dolichopoda cave crickets from Peloponnese (Orthoptera, Rhaphidophoridae): molecular and morphological investigations reveal four new species for Greece

Three species belonging to the genus Dolichopoda (Orthoptera; Rhaphidopohoridae) are known so far from the Peloponnese, all endemic to the area. In particular, D. matsakisi is known from two mountains in the North, while D. dalensi is present in the east region. The third species, D. unicolor, is distributed in the southern part of the Peloponnese, inhabiting caves on Mt Taygetos and Mani Peninsula. Recently, extensive sampling work in most of the Peloponnese has led to the discovery of new taxa, morphologically differentiated by the above three known species. To investigate the delimitation of the Peloponnesian species of Dolichopoda, we performed both morphological and molecular analyses. Morphological analysis was carried out by considering diagnostic characters generally used to distinguish different taxa, as the shape of epiphallus in males and the subgenital plate in females. Molecular analysis was performed by sequencing three mitochondrial genes, 12S rRNA, 16S rRNA, and COI, and one nuclear gene, 28S rRNA. Results from both morphological and molecular analyses were used to revise the taxonomic arrangement of the Peloponnesian species. On the whole, we were able to distinguish seven lineages of Peloponnesian Dolichopoda species, of which D. kofinasi n.sp., D.epidavrii n.sp., D. poseidonica n.sp., and D. propanti n.sp. are described as new species

Charged scalar production at the Compact Linear Collider for the S3⊗Z2S_3 \otimes \mathbb{Z}_2 model

We present a model with $S_3 \otimes \mathbb{Z}_2$ model plus a sterile neutrino and its phenomenological expectations for the production of charged scalars at the Compact Linear Collider. At tree level, our model predicts a total cross section in between 0.1 and $10^{-5}$ pb for the $e^- e^+ \to H^+ H^-$ process, considering all possible mass values for the charged scalar in the CLIC experiment. We also show that this prediction holds regardless of the masses of the other exotic particles and their couplings.Comment: arXiv admin note: substantial text overlap with arXiv:1810.02818; text overlap with arXiv:0808.3902 by other author

Prevention of Dermatologic Side Effects of Bimatoprost 0.03% Topical Therapy

PURPOSE: To investigate the efficacy of reducing the drop-skin contact to prevent dermatologic side effects of bimatoprost 0.03% topical therapy. DESIGN: Prospective, randomized, single-blinded, internally controlled study. METHODS: Enrolled subjects started bimatoprost 0.03% therapy once at night in both eyes and were instructed to wipe selectively only one eye (eye 1) with an adsorbent pad during and after drops administration for four months. The fellow eye acted as the internal control. Eyelash growth, regional skin hypertrichosis, and pigmentation on the periocular skin were assessed at baseline and during the four months of follow-up. RESULTS: A lower incidence of eyelash growth and skin pigmentation in the inferonasal pericanthal region were observed in eye 1. The incidence of pigmentation in the inferotemporal skin region and skin hypertrichosis were similar in the two eyes. CONCLUSION: The reduction of the drop,skin contact affects the regional incidence and the extent of dermatologic skin changes that are related to bimatoprost 0.03% topical therapy

Efalizumab

Introduction: Conventional systemic therapies for psoriasis are associated with serious toxicities that can limit long-term use. In recent years, biological therapies have offered the possibility of long-term therapy with improved safety and efficacy for the treatment of psoriasis. Biological therapies can be classified into three categories: the T-cell modulating agents (alefacept and efalizumab), the inhibitors of TNF-alpha (adalimumab, etanercept, infliximab) and the inhibitors of IL-12 and -23 (ustekinumab). Efalizumab is a humanized recombinant monoclonal IgG1 antibody. It targets multiple stages in the immunopathogenesis of psoriasis: initial T-cell activation, migration of T-cells into dermal and epidermal tissues, and T-cell reactivation. On 19 February 2009, the Committee for Medicinal Products for Human Use (CHMP) recommended the suspension of the marketing authorisation for efalizumab.Areas covered: Numerous clinical trials have demonstrated the efficacy, safety and health-related quality of life benefits of efalizumab in patients with moderate-to-severe chronic plaque psoriasis. Efalizumab was approved by the FDA in November 2003 and by the European Medicines Evaluation Agency in September 2004 for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. Recently, three cases of progressive multifocal leukoencephalopathy were described in patients on long-term (> 3 years) efalizumab therapy, leading to its withdrawal from the market.Expert opinion: Although initially favorable, the safety profile of efalizumab revealed the appearance of severe adverse events in long-term treated patients. Therefore, post-marketing surveillance is essential for correct evaluation of drug potential

Consensus on the use of the fixed combination calcipotriol/betamethasone dipropionate in the treatment of plaque psoriasis.

Calcipotriol, a vitamin D analogue, and betamethasone dipropionate, a high potency corticosteroid, are complementary agents for the topical treatment of psoriasis vulgaris. Robust evidence on the efficacy and safety of their fixed combination has been provided by randomized, double-blind, controlled clinical trials involving more than 7000 patients with the ointment formulation in psoriasis of the body and more than 4000 patients with the gel formulation in scalp psoriasis. These trials have shown that the fixed combination ointment is more effective and better tolerated, not only than placebo, but also than calcipotriol and tacalcitol monotherapies. In addition, it has proved, in most instances, to be more effective than betamethasone and at least as well tolerated. The same applies to the gel for scalp and body psoriasis. Safety studies have excluded that repeated courses of treatment with the fixed combination for up to one year produce systemic effects. Studies have also shown that the fixed combination treatment improves quality of life to a significantly greater extent than calcipotriol, with the once daily regimen most appreciated by patients, in both active disease and recurrency. Because of the extensive evidence, American and European guidelines recommend the calcipotriol/betamethasone dipropionate fixed combination a

Functional impairment of human resident cardiac stem cells by the cardiotoxic antineoplastic agent trastuzumab

Trastuzumab (TZM), a monoclonal antibody against the ERBB2 protein, increases survival in ERBB2-positive breast cancer patients. Its clinical use, however, is limited by cardiotoxicity. We sought to evaluate whether TZM cardiotoxicity involves inhibition of human adult cardiac-derived stem cells, in addition to previously reported direct adverse effects on cardiomyocytes. To test this idea, we exposed human cardiosphere-derived cells (hCDCs), a natural mixture of cardiac stem cells and supporting cells that has been shown to exert potent regenerative effects, to TZM and tested the effects in vitro and in vivo. We found that ERBB2 mRNA and protein are expressed in hCDCs at levels comparable to those in human myocardium. Although clinically relevant concentrations of TZM had no effect on proliferation, apoptosis, or size of the c-kit-positive hCDC subpopulation, in vitro assays demonstrated diminished potential for cardiogenic differentiation and impaired ability to form microvascular networks in TZM-treated cells. The functional benefit of hCDCs injected into the border zone of acutely infarcted mouse hearts was abrogated by TZM: infarcted animals treated with TZM + hCDCs had a lower ejection fraction, thinner infarct scar, and reduced capillary density in the infarct border zone compared with animals that received hCDCs alone (n = 12 per group). Collectively, these results indicate that TZM inhibits the cardiomyogenic and angiogenic capacities of hCDCs in vitro and abrogates the morphological and functional benefits of hCDC transplantation in vivo. Thus, TZM impairs the function of human resident cardiac stem cells, potentially contributing to TZM cardiotoxicity