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Necrotizing fasciitis (NF) is a highly aggressive infectious process, polymicrobial in nature, involving soft tissues with a high risk of rapid spread through superficial and deep fascial planes and muscular layers. Cervical NF is quite rare, is mostly of odontogenic origin, and may be complicated by descendant mediastinitis with a very high mortality rate. Systemic conditions impairing the patient’s immune competence, such as diabetes, may play a predisposing role. An effective treatment strategy includes prompt diagnosis (clinical findings, local microbiological tests, blood culture and, if deemed necessary, histopathology), broad-spectrum antibiotic therapy as early as possible which should be later adjusted according to antibiogram results, stabilization of vital functions and, if possible, elimination/treatment of predisposing factors. This paper describes a complex and emblematic case.

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA) or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST) when taken with an antihistamine but not in mild or moderate chronic idiopathic urticaria [urticaria without any possible secondary causes (ie, food additive or ASA and other NSAID hypersensitivity, or ASST)]. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angioedema, and exercise-induced anaphylaxis.

The background of this article is as follows: Few data are available about the persistence of serum-specific IgG antibodies to L. infantum after acute VL. The objective of this article is to evaluate the persistence of antibodies against L. infantum in patients healed from acute VL, and the kinetic of the same antibodies observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The methods which we used to obtain our objective are the following: 55 apparently immunocompetent, HIV-negative patients were examined for antibodies to L. infantum by IFAT over 14 years period, and we got the following results: Serum-specific IgG antibodies titers decrease slowly, but constantly. In the patients with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an initial reduction, and a subsequent antibody levels rapidly increase, while in the patients with a clinical and parasitological diagnosis of VL not responding to specific therapy, we demonstrated persistent high level of antibodies to L. infantum . Finally, we conclude that specific antibodies to L. infantum might persist for many years, and decrease slowly, but steadily. The persistence of these specific antibodies is not related to poor therapeutic response or prognosis, but an acute increase in their levels might be a sentinel of a VL relapse, while persistence of high antibody levels could suggest a resistance to therapy.

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered.

Type 2 diabetes is associated with a cluster of inter-related plasma lipid and lipoprotein abnormalities, including reduced HDL-C, a predominance of small, dense LDL and elevated triglycerides. These abnormalities occur even in prediabetes, before blood sugars rise sufficiently in order to confirm a diagnosis of diabetes, and this transition phase incurs important cardiovascular risk. This is the rationale for paying attention to dyslipidemia through the use of the hypolipidemic, rather than hypoglycemic drugs only. A literature search (by Medline and Scopus) was performed. The authors also manually reviewed the references of selected articles for any pertinent material. Beyond the ‘quantity’ of LDL, several lipid-lowering agents and particularly statins, are only in part beneficial on the ‘quality’ of LDL, so that their net effect on small, dense LDL is moderate. Among hypoglycemic agents, insulin and metformin have shown a limited role on small, dense LDL, while pioglitazone is more beneficial. The efficacy of incretin-based therapies on LDL subclasses remains to be tested by future studies, considering that preliminary studies have reported significant improvements by these agents on triglycerides and HDL-C plasma concentrations. Beyond hypolipidemic drugs, hypoglycemic agents have been found to be significantly effective in modulating levels of small, dense LDL, towards less atherogenic particles in patients with Type 2 diabetes. This may be linked to the reduction in cardiovascular risk obtained by these agents in this category of high-risk subjects.

In this study, lipid nanovesicular systems such as ethosome and transethosome dispersions were studied as potential vehicles for the cutaneous administration of genistein, an isoflavone with antioxidant and chemopreventive properties. The lipophilicity of genistein requires specialized delivery systems suitable for transdermal administration. Genistein loading in ethosomes and transethosomes, prepared by water injection and ethanol injection methods, was investigated. The evaluation of the dispersion macroscopic stability enabled the selection of transethosomes, produced by the ethanol injection method, loaded with genistein 0.25 mg/mL. The morphology of the vesicles was studied by cryogenic electron microscopy and by small‐angle x‐ray scattering, while the size distribution and the stability of genistein were evaluated for 3 months by photon correlation spectroscopy and high‐performance liquid chromatography, respectively. The results showed vesicle mean values of 111–145 nm, polydispersity indexes of 0.13–0.2, and drug entrapment capacity of 96% w/w. Transethosomes maintained physical‐chemical stability both as size distribution and genistein content. The zeta potential value ranged between −19 and −24 mV, while the pH of the formulation was around 5.5, suitable for skin application. Photochemiluminescence studies confirmed the antioxidant activity of genistein‐loaded transethosomes. The diffusion kinetics of genistein, studied in vitro by Franz cells, demonstrated that transethosomes increased the drug permeation threefold with respect to the genistein suspension. In view of a possible skin application, the transethosomes were thickened with 0.5% xanthan gum, selected through leakage and spreadability studies. Furthermore, tape stripping studies performed within 6 h after formulation application on the skin demonstrated a gradual increase of genistein content in the stratum corneum in the case of transethosome gel, compared to the conventional gel. The genistein‐loaded transethosome gel could exert a long‐lasting protection, crucial for preventing UV‐induced skin damage and photoaging.

We here investigated the anti-inflammatory activity of a polymethoxylated flavone-containing fraction (PMFF) from Citrus sinensis and of a prenylflavonoid-containing one (PFF) from Humulus lupulus, either alone or in combination (MIX). To this end, an in vitro model of inflammatory bowel disease (IBD), consisting of differentiated, interleukin (IL)-1β-stimulated Caco-2 cells, was employed. We demonstrated that non-cytotoxic concentrations of either PMFF or PFF or MIX reduced nitric oxide (NO) production while PFF and MIX, but not PMFF, also inhibited prostaglandin E2 release. Coherently, MIX suppressed both inducible NO synthase and cyclooxygenase-2 over-expression besides NF-κB activation. Moreover, MIX increased nuclear factor erythroid 2–related factor 2 (Nrf2) activation, heme oxygenase-1 expression, restoring GSH and reactive oxygen and nitrogen species (RONs) levels. Remarkably, these effects with MIX were stronger than those produced by PMFF or PFF alone. Noteworthy, nobiletin (NOB) and xanthohumol (XTM), two of the most represented phytochemicals in PMFF and PFF, respectively, synergistically inhibited RONs production. Overall, our results demonstrate that MIX enhances the anti-inflammatory and anti-oxidative effects of the individual fractions in a model of IBD, via a mechanism involving modulation of NF-κB and Nrf2 signalling. Synergistic interactions between NOB and XTM emerge as a relevant aspect underlying this evidence.

Air pollution has been associated with Parkinson’s Disease (PD) risk, although this relationship remains unclear. We estimated yearly levels of exposure to ten air pollutants (period 2006–2018) in an Italian population cohort, the Moli-sani study ( N  = 24,325; ≥35 years; 51.9% women), and derived three principal components, testing their associations with incident PD risk over 23,841 participants (213 cases, median(IQR) follow-up 11.2(2.0) years). This revealed a statistically significant association of PC1 (explaining 38.2% of common variance, tagging PM10 levels), independent on sociodemographic, professional and lifestyles covariates (Hazard Ratio [95%CI] = 1.04[1.02–1.07]). The association was confirmed testing average PM10 levels during follow-up (18[13–24]% increase of PD risk per 1 μg/m 3 increase of PM10). Among different circulating markers, lipoprotein a explained a significant proportion of this association (2.8[0.9; 8.4]%). These findings suggest PM10 as a target to lower PD risk at the population level and a potential implication of lipoprotein a in PD etiology.

We here investigated the anti-inflammatory activity of a polymethoxylated flavone-containing fraction (PMFF) from Citrus sinensis and of a prenylflavonoid-containing one (PFF) from Humulus lupulus, either alone or in combination (MIX). To this end, an in vitro model of inflammatory bowel disease (IBD), consisting of differentiated, interleukin (IL)-1β-stimulated Caco-2 cells, was employed. We demonstrated that non-cytotoxic concentrations of either PMFF or PFF or MIX reduced nitric oxide (NO) production while PFF and MIX, but not PMFF, also inhibited prostaglandin E[sub.2] release. Coherently, MIX suppressed both inducible NO synthase and cyclooxygenase-2 over-expression besides NF-κB activation. Moreover, MIX increased nuclear factor erythroid 2–related factor 2 (Nrf2) activation, heme oxygenase-1 expression, restoring GSH and reactive oxygen and nitrogen species (RONs) levels. Remarkably, these effects with MIX were stronger than those produced by PMFF or PFF alone. Noteworthy, nobiletin (NOB) and xanthohumol (XTM), two of the most represented phytochemicals in PMFF and PFF, respectively, synergistically inhibited RONs production. Overall, our results demonstrate that MIX enhances the anti-inflammatory and anti-oxidative effects of the individual fractions in a model of IBD, via a mechanism involving modulation of NF-κB and Nrf2 signalling. Synergistic interactions between NOB and XTM emerge as a relevant aspect underlying this evidence.