Nails: The Window to the Nose? Update on Yellow Nail Syndrome

Laura Vollono, Marco Adriano Chessa, Antonio Bruno, Michela Starace, Aurora Alessandrini, Bianca Maria Piraccini

Dermatol Pract Concept . 2020 Apr 3;10(2):e2020031. doi: 10.5826/dpc.1002a31.

Abstract

Background: Yellow nail syndrome is a rare condition characterized by typical nail alterations and variable presence of lymphedema and respiratory disease. The pathogenesis is still obscure, with most of the literature deriving from case reports and few investigations. The most reported respiratory conditions associated with yellow nail syndrome are pleural effusion and bronchiectasis, whereas association with rhinosinusitis is rarer.

Objectives: To describe a case of yellow nail syndrome and to provide a literature review regarding this disorder, discussing pathogenetic hypothesis, associated conditions, and therapeutic options.

Patients/methods: A 49-year-old man presented with arrested growth and alterations of his nails, without any history of previous trauma or inflammation but with a severe nasal septum deviation and a history of chronic rhinosinusitis. A diagnosis of yellow nail syndrome was made.

Results: Six months after undergoing rhinoseptoplasty and treatment with oral vitamin E, the patient’s nails were cured.

Conclusions: This case emphasizes the role of the dermatologist in detecting systemic conditions. The correct diagnosis led to complete resolution of both nail alterations and associated respiratory disorders.

Wagener BM, Anjum N, Evans C, Brandon A, Honavar J, Creighton J, Traber MG, Stuart RL, Stevens T, Pittet JF

Am J Respir Cell Mol Biol. 2020 Apr 3. doi: 10.1165/rcmb.2019-0185OC. [Epub ahead of print]

Abstract

Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The Type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen including increased lung permeability in a toll-like receptor 4/Rho A/plasminogen activator inhibitor (PAI)-1-dependent manner. Alpha-tocopherol has anti-inflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, Rho A and PAI-1 activation, stress fiber formation, P. aeruginosa T3SS exoenzyme (Exo Y) intoxication into host cells, and survival in a murine model of pneumonia in the presence of P. aeruginosa and pretreatment with α-tocopherol. We found that α-tocopherol alleviated P. aeruginosa-mediated alveolar endothelial and epithelial paracellular permeability by inhibiting RhoA, in part, via PAI-1 activation and increased survival in a mouse model of P. aeruginosa pneumonia. Furthermore, we found that α-tocopherol decreased the activation of RhoA and PAI-1 by blocking the injection of T3SS exoenzymes into alveolar epithelial cells. P. aeruginosa is becoming increasingly antibiotic-resistant. We provide evidence that α-tocopherol could be a useful therapeutic agent for individuals that are susceptible to infection with P. aeruginosa such as those who are immunocompromised or critically ill.

Ahmed AE, Alshehri A, Al-Kahtani MA, Elbehairi SEI, Alshehri MA, Shati AA, Alfaifi MY, Al-Doais AA, Taha R, Morsy K, El-Mansi AA

Biomed Pharmacother. 2020 Apr;124:109841. doi: 10.1016/j.biopha.2020.109841. Epub 2020 Jan 20.

Abstract

Avermectins are broad-spectrum antiparasitic drugs in veterinary and human medication. The current study aimed to examine the toxic effects of ivermectin (IVM) and doramectin (DRM), with or without co-treatment of vitamin E (Vit.E) and selenium (Se) on apoptosis, oxidative stress and male fertility in Wistar rats. Twenty five adult male animals were divided into five groups; G1; was control (CTL) received saline, G2; IVM (0.2 mg/kg b.w), G3; IVM plus Vit.E/Se (80/1.6 mg/kg b.w, respectively), G4; DRM (0.2 mg/kg b.w), and G5; DRM plus Vit.E/Se. Both IVM and DRM were given by subcutaneous (s.c) injections while Vit.E/Se was orally given. All treatments were administered once weekly for four consecutive weeks. By 24 h after the last treatment, the animals were sacrificed. Blood and tissue samples were collected for hematology, serobiochemistry, histopathology, and molecular assays for hepatic/ renal toxicities, oxidative stress, cell viability and fertility parameters. Apoptosis of the hepatic cells obtained from the treated rats was assayed by detection of annexin-V using the flow cytometric assay (FCA). The proliferating cellular nuclear antigen (PCNA) and DNA fragmentation in the treated rats’ testicular tissues were also assayed. Moreover, the direct effects of IVM or DRM with or without concomitant administration of Vit.E/Se on testicular cells isolated from adult rat were also performed in vitro. Apoptosis of those cultured testicular cells in response to the different treatments was assayed by detection of the inhibition-concentration fifty (IC₅₀) using the SRB method, and evaluating the viable versus apoptotic cells microscopically after staining with acridine orange-ethidium bromide (AO/EB). In conclusion, both avermectins induced apoptosis in the living and cultured cells, while those antioxidants; Vit.E and Se, reduced the oxidative stress and cytotoxicity both in vivo and in vitro, either. Furthermore, the reprotoxicity and reduced male fertility were seriously evoked by IVM, but not DRM with dramatic ameliorative effect of Vit.E/Se if concomitantly administered. Avermectins, especially ivermectin, should be given according to the dose recommended by the manufacturer company and repeated dosages should be given with Vit.E/Se.

Philip W Ind

Br J Hosp Med (Lond) . 2020 Apr 2;81(4):1-9. doi: 10.12968/hmed.2019.0371.

Abstract

E-cigarette or vaping product use-associated lung injury is a recently recognised, acute pulmonary syndrome which has been reported (particularly from June to October 2019) throughout the USA, but not in Europe (although one probable case, in the UK, has been reported; Medicines and Healthcare products Regulatory Agency, 2020). It presents acutely, most often in young men, as severe pulmonary consolidation, usually with respiratory failure. The mortality is around 2%. The cause(s) are unknown, but it is associated with vaping, particularly using unlicensed cannabis-containing products with tetrahydrocannabinol. Vitamin E acetate, often present in tetrahydrocannabinol-containing vape products as a solvent, has been implicated, as it has been identified in the bronchoalveolar lavage fluid of patients with e-cigarette or vaping product use-associated lung injury. This article reviews the recent literature, including clinical features, presentation and investigations, and possible mechanisms, in the context of vaping practices in the USA and the UK.

Veen L, Hantikainen E, Bellocco R, Ye W, Serafini M, Ponzano M, Grotta A, Trolle Lagerros Y

Eur J Nutr. 2020 Apr 2. doi: 10.1007/s00394-020-02239-8. [Epub ahead of print]

Abstract

PURPOSE:

Oxidative stress might play an important role in the development of osteoarthritis, but not much is known about the effect of antioxidants on osteoarthritis risk. We, therefore, aimed to investigate the effect of dietary vitamin C, E, beta-carotene, and non-enzymatic antioxidant capacity (NEAC), which measures overall antioxidant activity from the diet, on the risk of osteoarthritis.

METHODS:

For this study 43,865 men and women from the Swedish National March Cohort (SNMC) were followed for up to 19 years. We computed dietary intake of vitamin C, E and beta-carotene using information from a Food Frequency Questionnaire (FFQ). To estimate dietary NEAC we combined the information from the FFQ with food item-specific antioxidant capacity values from an antioxidant food database. Cases of osteoarthritis were identified through the Swedish National Patient Registers. We categorized all exposure variables into sex-specific quartiles and used multivariable-adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs).

RESULTS:

In total, we observed 5976 cases of OA during 469,148 person-years of follow-up. After adjusting for potential confounders, we did not find any association between vitamin C, beta-carotene and NEAC (p-values for trend > 0.5), but a positive association was found with higher dietary vitamin E intake (HR Q4 vs Q1: 1.11; 95% CI 1.02-1.21; p for trend = 0.01) and the risk of OA.

CONCLUSION:

Our findings do not provide evidence for dietary antioxidants to protect from the development of OA, and a higher dietary vitamin E intake might even increase the risk.

Zhang D, Wang B, Sun Y, Wang C, Mukherjee S, Yang C, Chen Y

Macromol Biosci. 2020 Apr 2:e2000036. doi: 10.1002/mabi.202000036. [Epub ahead of print]

Abstract

Burn wound healing remains a challenging health problem worldwide due to the lack of efficient and precise therapy. Inherent oxidative stress following burn injury is importantly responsible for prolonged inflammation, fibrotic scar, and multiple organ failure. Herein, a bioinspired antioxidative defense system coupling with in situ forming hydrogel, namely, multiresponsive injectable catechol-Fe³⁺ coordination hydrogel (MICH) matrix, is engineered to promote burn-wound dermal repair by inhibiting tissue oxidative stress. This MICH matrix serves as the special traits of “Fe-superoxide dismutases,” small molecular antioxidant (vitamin E), and extracellular matrix (ECM) in alleviating cellular oxidative damage, which demonstrates precise scavenging on reactive oxygen species (ROS) of different cellular locations, blocking lipid peroxidation and cell apoptosis. In in vivo burn-wound treatment, this MICH promptly integrates with injured surrounding tissue to provide hydration microenvironment and physicochemical ECM for burn wounds. Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re-epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn-wound care and other disease therapy induced by oxidative stress.

Yang CS, Luo P, Zeng Z, Wang H, Malafa M, Suh N

Mol Carcinog. 2020 Apr;59(4):365-389. doi: 10.1002/mc.23160. Epub 2020 Feb 3.

Abstract

α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ- and δ-forms of tocopherols and tocotrienols (T3). In comparison with α-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. γ-T3 and δ-T3 generally have even higher activities than γ-T and δ-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.

Li X, Jarosz AC, El-Sohemy A, Badawi A

Nutr Health. 2020 Mar 31:260106020912945. doi: 10.1177/0260106020912945. [Epub ahead of print]

Abstract

BACKGROUND:

Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as IL-1β at rs16944 contributed to a number of inflammatory disorders and may substantiate the convergance between chronic and infectious diseases.

AIM:

This study aims to identify the modifying effect of nutritional factors on the association between IL-1β genotypes and CXCL10 levels.

METHODS:

Participants (N = 386) were healthy males and females from the Toronto Nutrigenomics and Health study recruited from the University of Toronto. Levels of micronutrients and inflammatory markers were measured in plasma. IL-1β genotypes were extracted from the Affymetrix 6.0 SNP chip.

RESULTS:

CXCL10 levels were not different across different IL-1β genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (β = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (β = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (β = -0.016 ± 0.007, P = 0.012).

CONCLUSION:

The association between IL-1β rs16944 genotype and CXCL10 levels was modified by the levels of ascorbic acid, α-tocopherol and vitamin D. These findings may aid in understanding the combined effect of genetic and dietary factors in the development of various infectious and chronic diseases in which IL-1β and CXCL10 may play an etiological role.

Shvachko LP, Zavelevich MP, Gluzman DF, Telegeev GD

Exp Oncol. 2020 Mar;42(1):31-34.

Abstract

Placental-like alkaline phosphatase (PLAP) is expressed by many tumors and can be detected in sera of patients with various cancers. Its aberrant expression has been considered to be potentially useful as tumor marker. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear. The expression of various forms of AP in cells of chronic myeloid leukemia (CML) has not yet been studied.

AIM:

To analyze the expression patterns of various AP forms in cells originated from CML patients in blast crisis and to modify their expression by vitamin E.

MATERIALS AND METHODS:

RNA extracted from leukemic cells was converted to cDNA and real-time reverse transcription polymerase chain reaction was performed using SYBR Green protocol with primers to tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase and CCAAT-enhancer-binding proteins alpha (C/EBPα). To analyze the modulation of expression of APs and C/EBPα, CML cells were incubated with 100 µM vitamin E.

RESULTS:

We have observed the aberrant expression of mRNA intestinal alkaline phosphatase in CML cells that upon sequencing demonstrated the significant alignment with PLAP sequence while no gene homology with tissue placental alkaline phosphatase (PAP) was revealed. Vitamin E decreases mRNA PLAP expression and increases mRNA TNAP expression. Moreover, along with down-regulation of aberrant PLAP and up-regulation of TNAP, vitamin E increases C/EBPα mRNA expression.

CONCLUSION:

The loss of TNAP in CML may contribute to pathogenesis of this disease. PLAP may be considered as a putative target in differentiation therapies in myeloid neoplasms. Our findings suggest the potential role of vitamin E as the inducer of differentiation potential of leukemic cells in CML.