Nanosystems against candidiasis: a review of studies performed over the last two decades.

The crescent number of cases of candidiasis and the increase in the number of infections developed by non-albicans species and by multi-resistant strains has taken the attention of the scientific community, which has been searching for new therapeutic alternatives. Among the alternatives found the use of nanosystems for delivery of drugs already commercialized and new biomolecules have grown, in order to increase stability, solubility, optimize efficiency and reduce adverse effects. In view of the growing number of studies involving technological alternatives for the treatment of candidiasis, the present review came with the intention of gathering studies from the last two decades that used nanotechnology for the treatment of candidiasis, as well as analysing them critically and pointing out the future perspectives for their application with this purpose. Different studies were considered for the development of this review, addressing nanosystems such as metallic nanoparticles, mesoporous silica nanoparticles, polymeric nanoparticles, liposomes, nanoemulsion, microemulsion, solid lipid nanoparticle, nanostructured lipid carrier, lipidic nanocapsules and liquid crystals; and different clinical presentations of candidiasis. As a general overview, nanotechnology has proven to be an important ally for the treatment against the diversity of candidiasis found in the clinic, whether in increasing the effectiveness of commercialized drugs and reducing their adverse effects, as well as allowing exploring more effectively properties therapeutics of new biomolecules.

The Rise and Fall of Oral Ketoconazole.

BACKGROUND: Ketoconazole was the first broad-spectrum oral antifungal agent available to treat systemic and superficial mycoses. Evidence of hepatotoxicity associated with its use emerged within the first few years of its approval. Growing evidence of serious side effects including endocrine dysregulation, several drug interactions, and death led to the review of oral ketoconazole in 2011. OBJECTIVE: This article chronicles the use of oral ketoconazole from its introduction to its near replacement in medicine. CONCLUSION: Due to its hepatotoxic side effects, oral ketoconazole was withdrawn from the European and Australian markets in 2013. The United States imposed strict relabeling requirements and restrictions for prescription, with Canada issuing a risk communication echoing these concerns. Today, oral ketoconazole is only indicated for endemic mycoses, where alternatives are not available or feasible. Meanwhile, topical ketoconazole is effective, safe, and widely prescribed for superficial mycoses, particularly as the first-line treatment for tinea versicolor.

Stability in the cumulative incidence, severity and mortality of 101 cases of invasive mucormycosis in high-risk patients from 1995 to 2011: a comparison of eras immediately before and after the availability of voriconazole and echinocandin-amphotericin combination therapies.

As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995-2003) and E2, (2004-2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while 'other' dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival.

Onychomycosis therapy: past, present, future.

Methods to treat onychomycosis are varied, using therapies that can be categorized as topical, oral or device-related. Since their development, oral therapies have represented the gold standard for treatment over other methods. However, efficacy with oral therapies remains limited, and safety may be an issue, leaving many patients requiring alternative treatments. With research advances, topical therapies as alternatives for onychomycosis are being investigated with greater interest as new technologies are overcoming previous limitations of topical treatments, such as lack of nail penetration. New device-related topical therapy methods are particularly noteworthy, as they may allow for shorter, more convenient treatments for patients, reducing issues with topical compliance, and, in cases of non-drug light-based therapies, they will avoid potential for drug reactions. Research in these fields is preliminary, and the impact these methods may have on the future of onychomycosis remains to be seen.

Historical aspects of dermatomycoses.

Physicians have been aware of superficial fungal infections for centuries, but the causal agents and treatments of fungal infections remained unknown until the mid-1800s, when numerous important findings were reported. Among the relevant researchers in the field of superficial mycoses were Remak, who found the fungal nature of favus in 1837; Berg, who reported oral candidosis in 1841; and Wilkinson, who described vaginal candidosis in 1849. Tinea versicolor was described clinically in 1846 by Eichstedt, and its etiologic agent was identified in 1853. Beigel reported white piedra in 1856, and Cerqueira, tinea nigra in 1891. The book Les Tiegnes was published by Sabouraud in 1910, and black piedra infection was described by Horta in 1911. In 1927, Nannizzi reported the description of the sexual state of Microsporum gypseum. The current classification of dermatophytes was published by Emmons in 1934, and the taxonomy of yeast fungi was described by Lodder and Kreger-van Rij in 1952. Finally, the successful treatment of tinea capitis with griseofulvin by Gentles in 1958 saved many patients with tinea capitis from permanent hair loss, a common side effect after treatment with thallium. (c) 2010 Elsevier Inc. All rights reserved.

Fungal physiology and the origins of molecular biology.

Molecular biology has several distinct origins, but especially important are those contributed by fungal and yeast physiology, biochemistry and genetics. From the first gene action studies that became the basis of our understanding of the relationship between genes and proteins, through chromosome structure, mitochondrial genetics and membrane biogenesis, gene silencing and circadian clocks, studies with these organisms have yielded basic insight into these processes applicable to all eukaryotes. Examples are cited of pioneering studies with fungi that have stimulated new research in clinical medicine and agriculture; these studies include sexual interactions, cell stress responses, the cytoskeleton and pathogenesis. Studies with the yeasts and fungi have been effective in applying the techniques and insights gained from other types of experimental systems to research in fungal cell signalling, cell development and hyphal morphogenesis.

Antiviral, antifungal and antiprotozoal agents in the cinema.

Among the antimicrobial agents, antibacterials are the most frequently mentioned in cinematographic plots. Nevertheless, it is not uncommon to come across other antiviral agents, especially antiretrovirals and antiprotozoals. We analyzed the presence of antiviral and antifungal agents in different commercial films, both when they were merely mentioned in passing and when they played a major role in the film. This review essentially aims to address the historical portrayal of these agents in film and to list their appearances. The fictional treatments that appear in some films are not addressed.

Development of liposomal polyene antibiotics: an historical perspective.

PURPOSE: The purpose of this review article is to review the development of a number of liposomal polyene antibiotics. BACKGROUND: In the past thirty years, the increase in life-threatening pre-systemic and systemic fungal infections within cancer, diabetic and AIDS patients have reached alarming proportions. A number of antifungal agents have been developed to combat this problem. In particular, polyene antibiotics such as Amphotericin B (AmB) and Nystatin (Nys) have remained the most effective and widely used agents in the treatment of these infections. However, their administration is limited by dose-dependent toxicities. One such dose-limiting toxicity is renal toxicity. Polyene antibiotic-induced renal toxicity is believed to be mediated by the drug anchoring to cholesterol within the mammalian cell membrane, resulting in pore formation, abnormal electrolyte flux, decrease in adenosine triphosphate (ATP), and eventually a loss of cell viability. CONCLUSION: In the 1980s and 90s a number of promising lipid-based AmB and Nys formulations were developed to overcome these toxicities. This article will review the development of these liposomal polyene antibiotics.

Topical treatments for onychomycosis: a historical perspective.

Topical treatment of onychomycosis, in contrast to systemic oral therapy, allows the patient to apply medication directly to the affected area, thereby decreasing the potential for adverse events and drug interactions. Historically, several topical antifungal agents have been used in the treatment of onychomycosis; however, the evidence for their effectiveness is based on very limited data or anecdotal reports. Recently, the development of new, effective topical agents has renewed interest in this form of therapy. As clinical experience with newer topical agents expands, they may be found to be an effective option for the treatment of onychomycosis.

Antifungal antibiotics.

The search for new drugs against fungal infections is a major challenge to current research in mycotic diseases. The present article reviews the current types of antifungal infections, the current scenario of antifungal antibiotics, and the need and approaches to search for newer antifungal antibiotics and antifungal drug targets.

Ciclopirox nail lacquer and podiatric practice.

Ciclopirox 8% nail lacquer has recently been approved by the US Food and Drug Administration (FDA) for the management of mild-to-moderate dermatophytic onychomycosis not involving the lunula. Previously, the agents that were approved for the treatment of dermatophytic pedal onychomycosis--griseofulvin, itraconazole, and terbinafine--were administered orally. When ciclopirox nail lacquer is used, it is recommended that the infected nail undergo debridement by a health-care professional as frequently as monthly. It is important to be aware of the circumstances under which debridement of the mycotic nail may be considered medically necessary and therefore potentially eligible for reimbursement by third-party payers. For many nail presentations, nail debridement is an important component of a treatment protocol involving either the oral medications or the topical lacquer, as it serves to reduce the fungal load and ameliorate symptoms. With the availability of a new FDA-approved topical treatment alternative, it remains to be seen if podiatrists will embrace the definitive treatment of onychomycosis using the newer oral agents, the new nail lacquer, or both in combination with nail debridement to treat the disease.

[Manfred Plempel--his life and work]. / Manfred Plempel--Leben und Werk.

The biography of Dr. Manfred Plempel (1930-1994), Chief Mycologist of the Bayer AG, who developed the first antifungal azole, clotrimazole, for clinical applicability is presented.