Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans , Candida glabrata , Cryptococcus neoformans , and Malassezia furfur , including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro . An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents.

The incidence of life-threatening viral and microbial infections has dramatically increased over recent decades. Despite significant developments in anti-infective chemotherapy, many issues have increasingly narrowed the therapeutic options, making it imperative to discover new effective molecules. Among them, small peptides are arousing great interest. This review will focus in particular on a killer peptide, engineered from an anti-idiotypic recombinant antibody that mimics the activity of a wide-spectrum antimicrobial yeast killer toxin targeting β-glucan cell-wall receptors. The in vitro and in vivo antimicrobial, antiviral and immunomodulatory activities of killer peptide and its ability to spontaneously and reversibly self-assemble and slowly release its active dimeric form over time will be discussed as a novel paradigm of targeted auto-delivering drugs.

A phosphorylated peptide, named K40H, derived from the constant region of IgMs was detected in human serum by liquid chromatography coupled to high-resolution mass spectrometry. Synthetic K40H proved to exert a potent in vitro activity against fungal pathogens, and to inhibit HIV-1 replication in vitro and ex vivo. It also showed a therapeutic effect against an experimental infection by Candida albicans in the invertebrate model Galleria mellonella. K40H represents the proof of concept of the innate role that naturally occurring antibody fragments may exert against infectious agents, shedding a new light upon the posthumous role of antibodies and opening a new scenario on the multifaceted functionality of humoral immunity.

Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages Special Issue Editors: Candace S.-J. Tsai, Michael J. Ellenbecker This article is part of the topical collection on Nanotechnology, Occupational and Environmental Health Electronic supplementary material The online version of this article (of in vitro airway epithelial barrier model by manufactured nanomaterials.

High-aspect-ratio nanomaterials (HARN) (typically, single-walled carbon nanotubes (SWCNT) or multiwalled carbon nanotubes (MWCNT)) impair airway barrier function and are toxic to macrophages. Here, we assess the biological effects of nanotubes of imogolite (INT), a hydrated alumino-silicate [(OH)3Al2O3SiOH] occurring as single-walled NT, on murine macrophages and human airway epithelial cells. Cell viability was assessed with resazurin. RT-PCR was used to study the expression of Nos2 and Arg1, markers of classical or alternative macrophage activation, respectively, and nitrite concentration in the medium was determined to assess NO production. Epithelial barrier integrity was evaluated from the trans-epithelial electrical resistance (TEER). Potential genotoxicity of INT was assessed with comet and cytokinesis-block micronucleus cytome assays. Compared to MWCNT and SWCNT, INT caused much smaller effects on RAW264.7 and MH-S macrophage viability. The incubation of macrophages with INT at doses as high as 120 μg/cm(2) for 72 h did not alter either Nos2 or Arg1 expression nor did it increase NO production, whereas IL6 was induced in RAW264.7 cells but not in MH-S cells. INT did not show any genotoxic effect in RAW264.7 and A549 cells except for a decrease in DNA integrity observed in epithelial A549 cells after treatment with the highest dose (80 μg/cm(2)). No significant change in permeability was recorded in Calu-3 epithelial cell monolayers exposed to INT, whereas comparable doses of both SWCNT and MWCNT lowered TEER. Thus, in spite of their fibrous nature, INT appear not to be markedly toxic for in vitro models of lung-blood barrier cells.

Background: The abuse of antimicrobical drugs has increased the resistance of microorganisms to treatments, thus to make urinary tract infections (UTIs) more difficult to eradicate. Among natural substances used to prevent UTI, literature has provided preliminary data of the beneficial effects of D-mannose, N-acetylcysteine, and Morinda citrifolia fruit extract, due to their complementary mechanism of action which contributes respectively to limit bacteria adhesion to the urothelium, to destroy bacterial pathogenic biofilm, and to the anti-inflammatory and analgesic activity. The purpose of this study was to compare the administration of an association of D-mannose, N-acetylcysteine (NAC) and Morinda citrifolia extract versus antibiotic therapy in the prophylaxis of UTIs potentially associated with urological mini-invasive diagnostics procedures, in clinical model of the urodynamic investigation. Methods: 80 patients eligible for urodynamic examination, 42 men and 38 women, have been prospectively enrolled in the study and randomised in two groups (A and B) of 40 individuals. Patients of group A followed antibiotic therapy with Prulifloxacine, by mouth 400 mg/day for 5 days, while patients of the group B followed the association of mannose and NAC therapy, two vials/day for 7 days. Ten days after the urodynamic study, the patients were submitted to urine examination and urine culture. Results: The follow up assessment didn't show statistical significant difference between the two groups regarding the incidence of UTI. Conclusions: The association of mannose and NAC therapy resulted similar to the antibiotic therapy in preventing UTIs in patients submitted to urodynamic examination. This result leads to consider the possible use of these nutraceutical agents as a good alternative in the prophylaxis of the UTI afterwards urological procedures in urodynamics.

Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast killer phenomenon to the production of Ab-derived peptides characterized by in vitro and in vivo fungicidal activity will be focused. In particular, Abs that mimic the antimicrobial activity of a killer toxin (“antibiobodies”) and antifungal peptides derived from antibiobodies (killer peptide) and other unrelated Abs [complementarity determining regions (CDR)-based and constant region (Fc)-based synthetic peptides] are described. Mycological implications in terms of reevaluation of the yeast killer phenomenon, roles of antibiobodies in antifungal immunity, of β-glucans as antifungal targets and vaccines, and of Abs as sources of an unlimited number of sequences potentially active as new immunotherapeutic tools against fungal agents and related mycoses, are discussed.

Abstract. Background Every day worldwide women are diagnosed with malignant breast cancer with aggressiveness related to the age of patients (1). Today life expectancy of breast cancer patients is very high, but is often affected by the long-term side effects of oncological treatments. Breast tumors are often hormone-sensitive, and among the therapeutic options, endocrine therapy is currently used and includes tamoxifen, aromatase inhibitors and LHRH analogues (2). The decreased level of circulating estrogens due to the abovementioned therapy, in addition to the menopause condition, are responsible for atrophic vaginitis and urinary disorders. The latter are characterized by symptoms ranging from moderate to severe. Today an increasing interest on patient's quality of life is taken by physicians, especially medical oncologists, by focusing both on the most effective treatment and on minimizing the treatments' side-effects, including those of uro-gynecological nature. Estrogen deficiency due to the oncological treatments, chemotherapy and endocrine therapy, induces the uro-genital syndrome as much as is the case of postmenopausal women. The genitourinary postmenopausal syndrome is defined as a set of signs and symptoms associated with the reduction of circulating estrogens that determines changes in the vagina, vulva, bladder and urethra and that severely impairs women's quality of life.Women with breast cancer in endocrine adjuvant treatment, if not yet in physiological menopause, experience a temporary estrogen deficiency induced by the treatment itself. Similarly, to the aggressiveness of the tumor, the symptoms and signs of uro-genital syndrome may be more debilitating the younger the women are (3). The uro-genital symptoms of estrogen deficiency are vaginal dryness, burning and irritation, sexual symptoms such as the lack of lubrication and dyspareunia and urinary symptoms such as urgency, frequency, incontinence and recurrent urinary tract infections. The genitourinary syndrome, that is accompanied by atrophy of the urological mucosa, is characterized by recurrent bacterial cystitis and post-coital cystitis mostly incurred from gram-negative bacteria (4). The most bothersome urinary symptoms associated with bacteriuria are urgency, increasing voiding frequency, pain and urinary incontinence. Bacteria that colonize the bladder are mostly gram negative and of intestinal origin. They have a specific pathogenesis activity underlying the chronicity of the phenomenon which hardly 931