ACTH in invertebrates: A molecule for all seasons

In vertebrate and invertebrate models, adrenocorticotropic hormone (ACTH) belongs to the melanocortin group of related peptides, which share a common precursor, pro-opiomelanocortin (POMC). Functional experiments indicate that in invertebrates, ACTH plays a major role in several biological functions. ACTH, whose effects have been conserved during evolution more than its amino acidic sequence, is, directly or indirectly, able to contrast agents that perturb a body’s homeostasis. Here we review evidence highlighting the involvement of ACTH and ACTH-like molecules in the response of invertebrate models versus immune, environmental and parasitic challenges

Monitoring of the immune efficiency of Mytilus galloprovincialis in Adriatic sea mussel farms in 2005

The monthly evaluation of the cytotoxicity of hemolymph from the mussel Mytilus galloprovincialis revealed some variations in the percentage of cytotoxic animals during the year. Cytotoxicity is confirmed to be a dynamic parameter that can be used as an indicator of immune efficiency and, therefore, of the state of health of the animals

Targets and Effects of Yessotoxin, Okadaic Acid and Palytoxin: A Differential Review

In this review, we focus on processes, organs and systems targeted by the marine toxins yessotoxin (YTX), okadaic acid (OA) and palytoxin (PTX). The effects of YTX and their basis are analyzed from data collected in the mollusc Mytilus galloprovincialis, the annelid Enchytraeus crypticus, Swiss CD1 mice and invertebrate and vertebrate cell cultures. OA and PTX, two toxins with a better established mode of action, are analyzed with regard to their effects on development. The amphibian Xenopus laevis is used as a model, and the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) as the experimental protocol

Circulating phagocytes: The ancient and conserved interface between immune and neuroendocrine function

Immune and neuroendocrine functions display significant overlap in highly divergent and evolutionarily distant models such as molluscs, crustaceans, insects and mammals. Fundamental players in this crosstalk are professional phagocytes: macrophages in vertebrates and immunocytes in invertebrates. Although they have different developmental origins, macrophages and immunocytes possess comparable functions and differentiate under the control of evolutionarily conserved transcription factors. Macrophages and immunocytes share their pools of receptors, signalling molecules and pathways with neural cells and the neuro-endocrine system. In crustaceans, adult transdifferentiation of circulating haemocytes into neural cells has been documented recently. In light of developmental, molecular and functional evidence, we propose that the immune-neuroendocrine role of circulating phagocytes pre-dates the split of protostomian and deuterostomian superphyla and has been conserved during the evolution of the main groups of metazoans

Drosophila Helical factor is an inducible protein acting as an immune-regulated cytokine in S2 cells.

The innate immunity of Drosophila melanogaster is based on cellular and humoral components. Drosophila Helical factor (Hf), is a molecule previously discovered using an in silico approach and whose expression is controlled by the immune deficiency (Imd) pathway. Here we present evidence demonstrating that Hf is an inducible protein constitutively produced by the S2 hemocyte-derived cell line. Hf expression is stimulated by bacterial extracts that specifically trigger the Imd pathway. In absence of any bacterial challenge, the recombinant form of Hf can influence the expression of the antimicrobial peptides (AMPs) defensin but not drosomycin. These data suggest that in vitro Hf is an inducible and immune-regulated factor, with functions comparable to those of secreted vertebrate cytokine

Pain treatment with high-dose, controlled-release oxycodone: an Italian perspective

To investigate the possible role and tolerability of high-dose (>160 mg/day) oxycodone controlled release (CR) for the treatment of cancer and non-cancer pain. 227 patients with cancer or non-cancer pain were enrolled in an open-label, multi-center, Italian study in order to assess the adequacy of their existing pain management (using a numerical rating scale [NRS]) and the possible benefit high-dose oxycodone CR may offer patients experiencing uncontrolled pain. Results: Pain was poorly controlled at baseline, with only 18.1% of patients reporting adequate pain relief (NRS <3.5). All other patients reported uncontrolled pain, with an average NRS of 7.81. At baseline assessment, 47.89% of patients had been in pain for up to 3 months, 32.82% for 3–6 months, and 19.19% for more than 6 months. After baseline assessment, patients were switched to oxycodone CR monotherapy. The starting dose was individualized to each patient and titrated up over a 3- to 4-day period until effective pain management was achieved. Treatment was continued for an average of 37.24 days during the study. Pain control (final mean NRS of 2.85) was attained with an average dose of oxycodone CR 221.84 mg/day. Standard adverse events (including constipations, nausea, and vomiting) were recorded in 39.64% of patients receiving high-dose oxycodone CR monotherapy. Side-effects tended to subside after the initial week of treatment and did not result in any participants leaving the study. High-dose oxycodone CR can achieve rapid and effective management of moderate to severe cancer and non-cancer pain with minimum side-effects

The baseline comorbidity burden affects survival in elderly patients with acute myeloid leukemia receiving hypomethylating agents: Results from a multicentric clinical study

Background: In older patients with acute myeloid leukemia (AML), the definition of fitness, prognosis, and risk of death represents an open question. Methods: In the present study, we tested the impact on survival of disease- and patient-related parameters in a large cohort of elderly AML patients homogeneously assigned to treatment with hypomethylating agents (HMAs). Results: In 131 patients with a median age of 76 years, we confirmed that early response (&lt;0.001) and biology-based risk classification (p&nbsp;=&nbsp;0.003) can select patients with better-predicted survival. However, a full disease-oriented model had limitations in stratifying our patients, prompting us to investigate the impact of baseline comorbidities on overall survival basing on a comorbidity score. The albumin level (p&nbsp;=&nbsp;0.001) and the presence of lung disease (p&nbsp;=&nbsp;0.013) had a single-variable impact on prognosis. The baseline comorbidity burden was a powerful predictor of patients' frailty, correlating with increased incidence of adverse events, especially infections, and predicted overall survival (p &lt; 0.001). Conclusion: The comorbidity burden may contribute to impact prognosis in addition to disease biology. While the therapeutic armamentarium of elderly AML is improving, a comprehensive approach that combines AML biology with tailored interventions to patients' frailty is likely to fully exploit the anti-leukemia potential of novel drugs

The main actors involved in parasitization of Heliothis virescens larva

At the moment of parasitization by another insect, the host Heliothis larva is able to defend itself by the activation of humoral and cellular defenses characterized by unusual reactions of hemocytes in response to external stimuli. Here, we have combined light and electron microscopy, staining reactions, and immunocytochemical characterization to analyze the activation and deactivation of one of the most important immune responses involved in invertebrates defense, i.e., melanin production and deposition. The insect host/parasitoid system is a good model to study these events. The activated granulocytes of the host insect are a major repository of amyloid fibrils forming a lattice in the cell. Subsequently, the exocytosed amyloid lattice constitutes the template for melanin deposition in the hemocel. Furthermore, cross-talk between immune and neuroendocrine systems mediated by hormones, cytokines, and neuromodulators with the activation of stress-sensoring circuits to produce and release molecules such as adrenocorticotropin hormone, alpha melanocyte-stimulating hormone, and neutral endopeptidase occurs. Thus, parasitization promotes massive morphological and physiological modifications in the host insect hemocytes and mimics general stress conditions in which phenomena such as amyloid fibril formation, melanin polymerization, pro-inflammatory cytokine production, and activation of the adrenocorticotropin hormone system occur. These events observed in invertebrates are also reported in the literature for vertebrates, suggesting that this network of mechanisms and responses is maintained throughout evolution

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO

Objectives: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). Conclusions: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients