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Nutrients Jul 2022Vitamin A is a fat-soluble micronutrient necessary for the growth of healthy skin and hair. However, both too little and too much vitamin A has deleterious effects.... (Review)
Review
Vitamin A is a fat-soluble micronutrient necessary for the growth of healthy skin and hair. However, both too little and too much vitamin A has deleterious effects. Retinoic acid and retinal are the main active metabolites of vitamin A. Retinoic acid dose-dependently regulates hair follicle stem cells, influencing the functioning of the hair cycle, wound healing, and melanocyte stem cells. Retinoic acid also influences melanocyte differentiation and proliferation in a dose-dependent and temporal manner. Levels of retinoids decline when exposed to ultraviolet irradiation in the skin. Retinal is necessary for the phototransduction cascade that initiates melanogenesis but the source of that retinal is currently unknown. This review discusses new research on retinoids and their effects on the skin and hair.
Topics: Hair; Retinoids; Skin; Tretinoin; Vitamin A
PubMed: 35889909
DOI: 10.3390/nu14142952 -
Mycoses Jun 2021Approximately 70-75% of women will have vulvovaginal candidosis (VVC) at least once in their lifetime. In premenopausal, pregnant, asymptomatic and healthy women and... (Review)
Review
Approximately 70-75% of women will have vulvovaginal candidosis (VVC) at least once in their lifetime. In premenopausal, pregnant, asymptomatic and healthy women and women with acute VVC, Candida albicans is the predominant species. The diagnosis of VVC should be based on clinical symptoms and microscopic detection of pseudohyphae. Symptoms alone do not allow reliable differentiation of the causes of vaginitis. In recurrent or complicated cases, diagnostics should involve fungal culture with species identification. Serological determination of antibody titres has no role in VVC. Before the induction of therapy, VVC should always be medically confirmed. Acute VVC can be treated with local imidazoles, polyenes or ciclopirox olamine, using vaginal tablets, ovules or creams. Triazoles can also be prescribed orally, together with antifungal creams, for the treatment of the vulva. Commonly available antimycotics are generally well tolerated, and the different regimens show similarly good results. Antiseptics are potentially effective but act against the physiological vaginal flora. Neither a woman with asymptomatic colonisation nor an asymptomatic sexual partner should be treated. Women with chronic recurrent Candida albicans vulvovaginitis should undergo dose-reducing maintenance therapy with oral triazoles. Unnecessary antimycotic therapies should always be avoided, and non-albicans vaginitis should be treated with alternative antifungal agents. In the last 6 weeks of pregnancy, women should receive antifungal treatment to reduce the risk of vertical transmission, oral thrush and diaper dermatitis of the newborn. Local treatment is preferred during pregnancy.
Topics: Anti-Bacterial Agents; Antifungal Agents; Candida albicans; Candida glabrata; Candidiasis, Vulvovaginal; Causality; Ciclopirox; Contraceptive Agents; Diabetes Mellitus; Female; Hormones; Humans; Hyphae; Imidazoles; Infant, Newborn; Polyenes; Pregnancy; Vaginitis
PubMed: 33529414
DOI: 10.1111/myc.13248 -
BioMed Research International 2022Oxidative stress is one of the common factors leading to age-related eye diseases in older adults. Factors such as high oxygen consumption, high concentration of... (Review)
Review
Oxidative stress is one of the common factors leading to age-related eye diseases in older adults. Factors such as high oxygen consumption, high concentration of polyunsaturated fatty acids, and cumulative exposure to high-energy visible light in the eyes, lead to excessive generation of reactive oxygen species, hence triggering apoptosis of ocular cells and giving rise to ophthalmic diseases. Dietary supplements such as carotenoids, anthocyanins, and vitamins have antioxidant properties which may be of benefit in retaining better vision or reversing vision impairment; thus, studies have been conducted to understand the role of dietary supplements in the treatment or prevention of ophthalmic diseases. While high concentration of carotenoids such as lutein and zeaxanthin decrease the risk of developing age-related macular disease, anthocyanins and vitamins play a role in the treatment and prevention of other ophthalmic diseases: saffron extract reduced intraocular pressure in glaucoma patients; bilberry extract prevented impairments in lenses and retina, as well as alleviate symptoms of dry eye disease; high concentration of beta-carotene may reduce the risk of developing cataract. Further studies with clinical measurements are required to investigate the effectiveness of antioxidants on visual function and ophthalmic diseases.
Topics: Aged; Aging; Anthocyanins; Antioxidants; Carotenoids; Dietary Supplements; Humans; Lutein; Reactive Oxygen Species; Retina; Vitamin A; Vitamins; Zeaxanthins; beta Carotene
PubMed: 36225983
DOI: 10.1155/2022/5810373 -
Clinical Microbiology and Infection :... Nov 2020The goal of therapeutic drug monitoring (TDM) is to determine the appropriate exposure of difficult-to-manage medications to optimize the clinical outcomes in patients... (Review)
Review
BACKGROUND
The goal of therapeutic drug monitoring (TDM) is to determine the appropriate exposure of difficult-to-manage medications to optimize the clinical outcomes in patients in various clinical situations. Concerning antifungal treatment, and knowing that this procedure is expensive and time-consuming, TDM is particularly recommended for certain systemic antifungals: i.e., agents with a well-defined exposure-response relationship and unpredictable pharmacokinetic profile or narrow therapeutic index. Little evidence supports the routine use of TDM for polyenes (amphotericin B), echinocandins, fluconazole or new azoles such as isavuconazole, despite the fact that a better understanding of antifungal exposure may lead to a better response.
AIMS
The aim of this work is to review published pharmacokinetic/pharmacodynamic data on systemically administered antifungals, focusing on those for which monitoring is not routinely recommended by experts.
SOURCES
A MEDLINE search of the literature in English was performed introducing the following search terms: amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, triazoles, caspofungin, micafungin, anidulafungin, echinocandins, pharmacokinetics, pharmacodynamics, and therapeutic drug monitoring. Review articles and guidelines were also screened.
CONTENT
This review collects different pharmacokinetic/pharmacodynamic aspects of systemic antifungals and summarizes recent threshold values for clinical outcomes and adverse events. Although for polyenes, echinocandins, fluconazole and isavuconazole extensive clinical validation is still required for a clear threshold and a routine monitoring recommendation, particular points such as liposome structure or complex pathophysiological conditions affecting final exposure are discussed. For the rest, their better-defined exposure-response/toxicity relationships allow access to useful threshold values and to justify routine monitoring. Additionally, clinical data are needed to better define thresholds that can minimize the development of antifungal resistance.
IMPLICATIONS
General TDM for all systemic antifungals is not recommended; however, this approach may help to establish an adequate antifungal exposure for a favourable response, prevention of toxicity or development of resistance in special clinical circumstances.
Topics: Antifungal Agents; Drug Monitoring; Echinocandins; Fluconazole; Humans; Mycoses; Nitriles; Polyenes; Practice Guidelines as Topic; Pyridines; Triazoles
PubMed: 32535150
DOI: 10.1016/j.cmi.2020.05.037 -
Nature Nov 2023Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model. Recently, the clinically vital...
Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification yielded a new polyene, AM-2-19, that is renal sparing in mice and primary human renal cells, potent against hundreds of pathogenic fungal strains, resistance evasive following serial passage in vitro and highly efficacious in animal models of invasive fungal infections. Thus, rational tuning of the dynamics of interactions between small molecules may lead to better treatments for fungal infections that still kill millions of people annually and potentially other resistance-evasive antimicrobials, including those that have recently been shown to operate through supramolecular structures that target specific lipids.
Topics: Animals; Humans; Mice; Amphotericin B; Antifungal Agents; Cells, Cultured; Cholesterol; Drug Resistance, Fungal; Ergosterol; Kidney; Kinetics; Microbial Sensitivity Tests; Mycoses; Polyenes; Serial Passage; Sterols; Time Factors
PubMed: 37938782
DOI: 10.1038/s41586-023-06710-4 -
Ophthalmology Mar 2020
Topics: Eye Diseases; Fatty Acids, Omega-3; Humans; Lutein; Macular Degeneration; Zeaxanthins; Zinc; beta Carotene
PubMed: 32087877
DOI: 10.1016/j.ophtha.2019.10.033 -
Infectious Disease Clinics of North... Jun 2021Over the past 15 years, there has been an increase in the development and utilization of newer antifungal agents. The ideal antifungal, however, in regard to spectrum... (Review)
Review
Over the past 15 years, there has been an increase in the development and utilization of newer antifungal agents. The ideal antifungal, however, in regard to spectrum of activity, pharmacokinetic/pharmacodynamic properties, development of resistance, safety, and drug interaction profile remains elusive. This article reviews pharmacologic aspects of Food and Drug Administration-approved polyenes, flucytosine, azoles, and echinocandins as well as promising pipeline antifungal agents. Unique properties of these newer agents are highlighted. The clinical role of established and investigational antifungal agents as treatment and/or prevention of invasive fungal infections is discussed.
Topics: Antifungal Agents; Azoles; Drugs, Investigational; Echinocandins; Flucytosine; Humans; Mycoses; Polyenes; United States
PubMed: 34016281
DOI: 10.1016/j.idc.2021.03.005 -
Molecules (Basel, Switzerland) Mar 2021In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of... (Review)
Review
In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of complex molecules is the Diels-Alder cycloaddition. This reaction is between a diene and a dienophile. Among the most important dienes are the cyclic dienes, as they facilitate the reaction. This review considers the synthesis and reactivity of one of these dienes with special characteristics-it is cyclic and has an electron withdrawing group. This building block has been used for the synthesis of biologically active compounds and is present in natural compounds with interesting properties.
Topics: Cycloaddition Reaction; Molecular Structure; Polyenes; Stereoisomerism
PubMed: 33809941
DOI: 10.3390/molecules26061772 -
Methods in Enzymology 2020Vitamin A and derivatives, the natural retinoids, underpin signaling pathways of cellular differentiation, and are key chromophores in vision. These functions depend on...
Vitamin A and derivatives, the natural retinoids, underpin signaling pathways of cellular differentiation, and are key chromophores in vision. These functions depend on transfer across membranes, and carrier proteins to shuttle retinoids to specific cell compartments. Natural retinoids, ultimately derived from plant carotenoids by metabolism to all-trans retinol, are lipophilic and consist of a cyclohexenyl (β-ionone) moiety linked to a polyene chain. This structure constrains the orientation of retinoids within lipid membranes. Cis-trans isomerization at double bonds of the polyene chain and s-cis/s-trans rotational isomerization at single bonds define the functional dichotomy of retinoids (signaling/vision) and specificities of interactions with specific carrier proteins and receptors. Metabolism of all-trans retinol to 11-cis retinal, transfer to photoreceptors, and removal and recycling of all-trans retinal generated by photoreceptor irradiation, is the key process underlying vision. All-trans retinol transferred into cells is metabolized to all-trans retinoic acid and shuttled to the cell nucleus to regulate gene expression controlling organ, tissue and cell differentiation, and cellular homeostasis. Research methods need to address the potential of photoisomerization in vitro to confound research results, and data should be interpreted in the context of membrane-association properties of retinoids and physiological concentrations in vivo. Despite a century of research, there are many fundamental questions of retinoid cellular biochemistry and molecular biology still to be answered. Computational modeling techniques will have an important role for understanding the nuances of vitamin A signaling and function.
Topics: Carotenoids; Retina; Retinaldehyde; Retinoids; Vitamin A
PubMed: 32359642
DOI: 10.1016/bs.mie.2020.02.002 -
Methods in Enzymology 2022More than 600 different carotenoids have been isolated from natural sources and fully or partly characterized. Fortunately, although they are all different individual...
More than 600 different carotenoids have been isolated from natural sources and fully or partly characterized. Fortunately, although they are all different individual compounds, the carotenoids may be considered as a group in terms of many of their basic properties. The aim of this chapter is to help newcomers and others that are not carotenoid specialists to understand the peculiarities of carotenoids, and how best to work with them. The basic principles of structure and nomenclature of carotenoids are described (especially the IUPAC semi-systematic rules) and the chemical and physical properties on which the biological functions depend are discussed. Guidance is given on how to handle and work with carotenoids safely and reliably and reduce the risk of forming artifacts and introducing impurities. Recommendations are made about their isolation, identification by various physical methods, and spectrophotometric quantitative analysis. Structural features that determine the shape of the carotenoid molecule are discussed, especially the conjugated polyene system. This also determines the light absorption properties of carotenoids and their chemical reactivity, especially toward oxidising agents. The properties of carotenoids in situ are strongly influenced by aggregation in the aqueous environment and by interactions with other molecules in their vicinity, notably proteins and membrane lipids. Many substances that look like fragments of carotenoids have been isolated from natural sources. This chapter does not provide comprehensive coverage of these apocarotenoids, but does consider their nomenclature and numbering according to the IUPAC rules.
Topics: Carotenoids; Proteins
PubMed: 35871833
DOI: 10.1016/bs.mie.2022.04.005