Increased Rates of Gold and Acrylate Allergy in Individuals with Fibromyalgia Tested with an Extended Dental Patch Test Series.

Fibromyalgia is a common chronic pain condition. Rates of contact allergy in individuals with fibromyalgia have not been widely studied. Systemic contact allergy can present with muscle and joint pain and general malaise. The aim of this study is to investigate contact allergy rates in individuals with fibromyalgia to the sensitizers in an extended dental series and compare with control groups. Contact allergy to gold was significantly more common in the fibromyalgia group than the dermatitis control group. When corrected for patch test system, contact allergy to gold was significantly more common in the fibromyalgia group than the dental control group. Contact allergy to hydroxyethyl methacrylate and grouped acrylates and methacrylates was significantly more common in the fibromyalgia group than the dental control group. In conclusion, individuals with fibromyalgia may have a propensity to sensitization to gold, either via an increased exposure or an alteration in the oral environment. Gold is also implicated in systemic contact dermatitis and may be a factor in elicitation of symptoms in individuals with fibromyalgia. Acrylate allergy is also common in the fibromyalgia population and may be a consequence of occupational exposure or dental treatment.

Gold Nanoparticles Reduce Food Sensation in Caenorhabditis elegans via the Voltage-Gated Channel EGL-19.

Introduction: The increasing use of gold nanoparticles (Au NPs) in the medical field has raised concerns about the potential adverse effect of Au NPs exposure. However, it is difficult to assess the health risks of Au NPs exposure at the individual organ level using current measurement techniques. Methods: The physical and chemical properties of Au NPs were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR), and zeta sizer. The RNA-seq data of Au NPs-exposed worms were analyzed. The food intake was measured by liquid culture and Pharyngeal pumping rate. The function of the smell and taste neurons was evaluated by the chemotaxis and avoidance assay. The activation of ASE neurons was analyzed by calcium imaging. The gene expression of ins-22 and egl-19 was obtained from the C. elegans single cell RNA-seq databases. Results: Our data analysis indicated that 62.8% of the significantly altered genes were functional in the nervous system. Notably, developmental stage analysis demonstrated that exposure to Au NPs interfered with animal development by regulating foraging behavior. Also, our chemotaxis results showed that exposure to Au NPs reduced the sensation of C. elegans to NaCl, which was consistent with the decrease in calcium transit of ASEL. Further studies confirmed that the reduced calcium transit was dependent on voltage-gated calcium channel EGL-19. The neuropeptide INS-22 was partially involved in Au NPs-induced NaCl sensation defect. Therefore, we proposed that Au NPs reduced the calcium transit in the ASEL neuron through egl-19-dependent calcium channels. It was partially regulated by the DAF-16 targeting neuropeptide INS-22. Discussion: Our results demonstrate that Au NPs affect food sensation by reducing the calcium transit in ASEL neurons, which further leads to reduced pharynx pumping and feeding defects. The toxicology studies of Au NPs from worms have great potential to guide the usage of Au NPs in the medical field such as targeted drug delivery.

Attenuation of diethylnitrosamine-induced hepatocellular carcinoma in a rat model by combination therapy of diacerein and gold nanoparticles: a histopathological and immunohistochemical study.

The purpose of this study was to investigate the effect of combined therapy of diacerein and gold nanoparticles (AuNP) on diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in a rat model. Normal healthy and DEN-induced (HCC) rats were divided into five groups. Group I healthy rats served as normal control, Group II untreated HCC rats, Group III HCC rats administered diacerein, Group IV HCC rats administered AuNP, and Group V HCC rats administered diacerein and AuNP. All treatments were given once daily for 4 weeks. Liver morphology and necroinflammation in all groups were evaluated using hematoxylin and eosin (H&E), Masson's trichrome for fibrosis, and immunohistochemistry assays for expression of TNF-α, IL-6, ß-catenin, and caspase-3. Liver sections from Group II HCC rats showed loss of lobular architecture, thick fibrous tissue deposition, leukocyte infiltration, degenerated hepatocytes and HCC neoplastic nodules surrounded by extensive fibrosis. Group II had high expression of TNF-α, IL-6, and ß-catenin, and low caspase-3 expression as compared to Group I. HCC rats treated with the combined therapy of diacerein and AuNP (Group V) showed markedly decreased HCC lesions, significant necroinflammation reduction (p ˂ 0.05) and 90% reduction in fibrosis as compared to Group II HCC + diacerein. This combined therapy also reduced (p ˂ 0.05) TNF-α, IL-6, ß-catenin expression and increased caspase-3 expression. In conclusion, diacerein combined with AuNP synergistically attenuated the severity of HCC lesions by reducing necroinflammation and fibrosis, decreased TNF-α, IL-6, ß-catenin expression, and increased caspase-3 expression for apoptosis.

A Retrospective Review of Late Delayed Positive Patch Testing Greater Than Day 8 at Mayo Clinic From 2001 to 2020.

BACKGROUND: Patch tests are read between days 5 and 7, because most hypersensitivity reactions occur within 7 days. Later reactions can occur after day 8, which may be missed. OBJECTIVE: The aim of the study was to review all late delayed positive (LDP) reactions that have occurred after day 8 at Mayo Clinic from 2001 to 2020. METHODS: Mayo Clinic records were reviewed for patients who had patch test readings performed at greater than day 8. Late delayed positive reactions were defined as any patch tests that were initially negative from days 4 to 7 yet became positive after day 8. RESULTS: Two hundred seventy-four patients developed 439 LDPs to 89 allergens. Fourteen allergens had LDPs in at least 2% of patients: gold (gold sodium thiosulfate-3 concentrations, gold chloride, potassium dicyanoaurate), cobalt (cobalt sulfate, cobalt chloride hexahydrate), beryllium, palladium, acrylates (2-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate), dodecyl gallate, and gentamycin. Late delayed positive reactions to gold allergens were the most frequent reactions. Up to 90% of relevant gold allergen LDPs were positive by day 15. CONCLUSIONS: Positive patch test readings after day 8 are uncommon, but allergens most likely to be positive are metals (gold, cobalt, palladium, beryllium), acrylates, dodecyl gallate, and gentamycin. Gold allergens showed the highest LDP rates and relevance, with most reactions occurring by day 15.

[Nonspecific inflammatory reaction after implantation of palpebral implants]. / Nespetsificheskaya vospalitel'naya reaktsiya posle implantatsii pal'pebral'nogo implantata.

PURPOSE: To identify the possible cause of an inflammatory reaction to a Russian-manufactured palpebral implant made of gold in the long term after surgery, and to determine the clinical and morphological changes in the tissues of the upper eyelid when the presence of the implant caused the inflammatory reaction. MATERIAL AND METHODS: The results of 150 operations with placement of a palpebral implant were analyzed. In 12 cases, a nonspecific inflammatory reaction was revealed within 2 to 4 weeks after the operation, in 7 cases it necessitated explantation, in 5 cases the local long-term use of an ointment with a corticosteroid made it possible to avoid extrusion and explantation. Chemical microanalysis of the palpebral implant and fragments of the removed capsule was performed using scanning electron microscopy (SEM), as well as immunohistochemical (IHC), macro- and microscopic examination of the fragments of connective tissue capsule was carried out after removal of the palpebral implant. RESULTS: The obtained data confirm the chemical purity of the implant, the absence of abnormal accumulation of metals in the tissues of the eyelid. IHC, macro- and microscopic examination of the presented fragments of the connective tissue capsule revealed signs characteristic of an inflammatory reaction to a foreign body. CONCLUSION: Further research is needed to establish the factors and predictors for the development of inflammatory reactions to a foreign body and, in particular, to gold.

The Value of CTA Based on Gold Nanorod Contrast Agent in Coronary Artery Diagnosis and Plaque Property Analysis.

Coronary CT angiography (CTA) with the characteristics of noninvasive and simple operation is widely used in the diagnosis of coronary artery stenosis. The choice of contrast agent exerts an important impact on the imaging quality of CTA. Conventional iodine contrast agents are easily excreted by the kidneys, from which the imaging window is short, and the imaging quality is poor. Metal nanomaterials have unique optical properties and have broad application prospects in imaging. Our aim is to explore the value of gold nanorod contrast agent in the diagnosis of coronary heart disease. A gold nanorod suspension was first prepared, and the prepared gold nanorod was uniform and had good dispersibility. It can be seen from the light absorption curve that there are two obvious peaks on the UV absorption peak of the gold nanorods. The gold nanorods were cultured in different solutions, and it was found that the particle size of the gold nanorods did not change significantly within 72 hours, indicating that the prepared gold nanorods had good stability. When observing the damage degree of mouse kidney tissue, it was shown that the damage degree of gold nanorod contrast agent to mouse kidney tissue was less than that of iodine contrast agent. The above results indicate that the gold nanorod contrast agent has good stability and safety. Therefore, our study demonstrated that the gold nanorod contrast agent has high value in the diagnosis of coronary arteries and the analysis of plaque properties.

Relative expression of microRNAs, apoptosis, and ultrastructure anomalies induced by gold nanoparticles in Trachyderma hispida (Coleoptera: Tenebrionidae).

The extensive use of nanomaterials generates toxic effects on non-target species and the ecosystem. Although gold nanoparticles (Au-NPs) are generally expected to be safe, the recent study contains conflicting data regarding their cytotoxicity in the darkling beetles Trachyderma hispida. The study postulated cellular perturbation in the ovarian tissue of the beetles induced by a sublethal dose of Au-NPs (0.01 mg/g). When compared with the controls, a significant inhibition in the activities of the antioxidant enzymes selenium-dependent (GPOX) and selenium-independent (GSTP) glutathione peroxidases (GPx) was observed in the treated beetles. The study proposed microRNAs (miRNA-282 and miRNA-989) as genotoxic markers for the first time, reporting a significant suppression in their transcriptional levels in the treated beetles. Furthermore, TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) and flow cytometry assays (annexin V-Fitc) indicated a significant increase in ovarian cell apoptosis in the treated beetles. Additionally, an ultrastructure examination revealed pathological changes in the ovarian cells of the treated beetles. The resulting anomalies in the present study may interrupt the fecundity of the beetles and lead to the future suppression of beetle populations.

Discriminatory alteration of carbohydrate homeostasis by gold nanoparticles ingestion in Drosophila.

With the extensive usage of gold nanoparticles (AuNPs) in various industrial sectors and biomedical applications, evaluation of their possible effects on human health becomes imperative. Therefore, the present study was aimed toward assessing the dose-dependent impact of AuNPs ingestion on metabolic homeostasis using Drosophila melanogaster as a model system. We found that larval ingestion of higher dose of AuNPs significantly reduced body weight. Further analysis of the crucial energy reservoir showed selective alteration in carbohydrate levels without any change in the lipid and protein levels. Transcriptional downregulation of glycogen synthase further supported impaired glycogen metabolism in flies supplemented with higher dose of AuNPs. Additionally, ingestion of higher dose of AuNPs in larvae results in significantly increased levels of reactive oxygen species (ROS) in the peripheral tissues, suggestive of stress condition. Our findings clearly imply that supplementing higher doses of AuNPs at an early developmental stage can potentially cause weight loss, impair glycogen metabolism, and elevate ROS production. Therefore, determination of a biologically effective dose is critical for the safety of mankind and vulnerable populations at the workplace.

Gold-based therapy: From past to present.

Despite an abundant literature on gold nanoparticles use for biomedicine, only a few of the gold-based nanodevices are currently tested in clinical trials, and none of them are approved by health agencies. Conversely, ionic gold has been used for decades to treat human rheumatoid arthritis and benefits from 70-y hindsight on medical use. With a view to open up new perspectives in gold nanoparticles research and medical use, we revisit here the literature on therapeutic gold salts. We first summarize the literature on gold salt pharmacokinetics, therapeutic effects, adverse reactions, and the present repurposing of these ancient drugs. Owing to these readings, we evidence the existence of a common metabolism of gold nanoparticles and gold ions and propose to use gold salts as a "shortcut" to assess the long-term effects of gold nanoparticles, such as their fate and toxicity, which remain challenging questions nowadays. Moreover, one of gold salts side effects (i.e., a blue discoloration of the skin exposed to light) leads us to propose a strategy to biosynthesize large gold nanoparticles from gold salts using light irradiation. These hypotheses, which will be further investigated in the near future, open up new avenues in the field of ionic gold and gold nanoparticles-based therapies.

Gold nanoparticles disrupt actin organization and pulmonary endothelial barriers.

This study explored the impact of gold nanoparticles on the metabolic activity and morphology of human pulmonary endothelial cell monolayers. We developed a gold nanoparticle library of three different sizes and two surface chemistries that include anionic citrate and the cationic polyelectrolyte poly(allylamine hydrochloride). The nanoparticles were characterized in cell culture medium to assess how their physical properties are altered after exposure to biological fluids. A bovine serum albumin pretreatment protocol was developed to stabilize the nanoparticles in cell culture medium. Results of this study show that an 18 h exposure of human pulmonary artery endothelial cells to the different nanoparticles modestly affects cellular metabolic activity. However, nanoparticle exposure perturbs the cortical actin networks and induces the formation of intercellular gaps. In particular, exposure to the poly(allylamine hydrochloride)-coated particles reduces the area of cell-cell junctions-a change that correlates with increased leakiness of endothelial barriers. The presence of excess polyelectrolyte capping agents in the supernatant of poly(allylamine hydrochloride)-coated nanoparticles significantly impacts endothelial morphology. Pretreatment of the particle supernatant with bovine serum albumin mitigates the negative effects of free or bound polyelectrolytes on endothelial cell monolayers.

DNA damage analysis concerning GSTM1 and GSTT1 gene polymorphism in gold jewellery workers from Peshawar Pakistan.

PURPOSE: To evaluate the genotoxic effects of gold jewellery fumes and its association with GSTM1 and GSTT1 genetic polymorphisms. MATERIALS AND METHODS: We examined 94 subjects including 54 gold jewellery workers and 40 controls. The DNA damage was evaluated by alkaline comet assay and genotyping by PCR. RESULTS: The mean total comet score (TCS) in gold jewellery workers was significantly higher as compared to the control subjects (128.0 ± 60.6 versus 47.7 ± 21.4; p = 0.0001). Duration of occupational exposure had positive correlation (r = 0.453, p < 0.01) with DNA damage. Age and tobacco use had significant effects on the TCS of the exposed group as compared to the control group (p < 0.05). The frequency of the GSTM1-null genotype in the exposed group was significant (p = 0.004) as compared to the control group. No significant association (p > 0.05) between the GSTM1 and GSTT1 genotypes and DNA damage was found. CONCLUSIONS: Our results suggest that there is increased DNA damage in gold jewellery workers due to their occupational surroundings. Hence there is a strong need to educate the workers about the adverse health effects of potentially hazardous chemicals and highlight the importance of using protective measures.

Higher Prevalence of Nickel and Palladium Hypersensitivity in Patients with Ulcerative Colitis.

BACKGROUND: The etiology of ulcerative colitis (UC) remains elusive even though many genetic and environmental pathogenic factors have been reported. Aberrant inflammatory responses mediated by specific subsets of T cells have been observed in ulcerative lesions of UC patients. OBJECTIVES: To elucidate the involvement of a delayed-type hypersensitivity reaction in UC, we focused on dental metal hypersensitivity, a T cell-mediated, delayed-type allergic reaction that causes oral contact mucositis and systemic cutaneous inflammation. METHOD: We recruited 65 Japanese UC patients and 22 healthy controls (HC) and used the in vitro lymphocyte stimulation test to quantify their sensitivity to zinc, gold, nickel, and palladium - the metals that have been widely used in dentistry. All subjects were users of metallic dental implants and/or prostheses containing zinc, gold, nickel, and/or palladium as major constituents. RESULTS: Sixty percent of the UC patients were hypersensitive to at least one metal species, whereas 32% of the HC were hypersensitive to only a single metal species. The overall incidence of metal hypersensitivity was significantly higher for UC patients than for HC. Furthermore, a significantly greater proportion of UC patients were hypersensitive to nickel or palladium. The severity of the sensitivity to nickel and palladium was also significantly greater for UC patients than for HC. CONCLUSIONS: This pilot study demonstrates that UC patients have a significantly higher incidence of hypersensitivity to nickel and palladium, suggesting the possible involvement of dental metal hypersensitivity in UC pathogenesis.

Alcohol-Related Dermatitis: A Review.

: Wine, beer, liquor, and spirits are widely consumed in many cultures across the globe, and for some individuals, ingestion, cutaneous contact, or other exposure can lead to dermatologic findings. However, there currently exist no comprehensive reviews on alcohol-related dermatitis. Herein, we will provide an overview of alcohol-related dermatitis and contact urticaria, including the epidemiology and clinical manifestations, potential allergens found in alcoholic beverages, testing approaches, and strategies for allergen avoidance.

Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics.

Due to the high toxicity of currently used chemotherapeutics, novel methods of cancer treatment are needed. Gold nanoparticles (AuNPs) seem to be an interesting alternative due to penetration through biological membranes and systemic barriers. AuNPs as carriers of chemotherapeutics allow for reduced concentrations whilst maintaining the expected effect, and thus reducing the costs of therapy and adverse effects. We synthesized AuNPs stabilized with reduced glutathione (GSH) and conjugated with doxorubicin (DOX), gemcitabine (GEM) or cytarabine (CTA). This is the first study in which cytarabine-AuNPs were synthesized and characterized. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), nuclear magnetic resonance spectroscopy (NMR) and high-performance liquid chromatography (HPLC) were used to chemically characterize obtained nanoparticles. Antitumor activity and safety of application were assessed by MTT assay in in vitro model (human osteosarcoma cells -143B, human osteoblast- hFOB1.19, breast cancer cells - MCF7, breast epithelial cells - MCF10A, pancreatic cancer cells - PANC-1, and pancreatic cells - hTERT-HPNE cells). We have shown that cellular response varies according to the type and concentration of AuNPs. At some concentrations, we were able to show selective cytotoxicity of our AuNPs conjugates only to cancer cell lines. Synthesized nanoparticles were more cytotoxic to tumor cell lines than chemotherapeutics alone.

Gold nanoclusters elicit homeostatic perturbations in glioblastoma cells and adaptive changes of lysosomes.

Unique physicochemical features place gold nanoclusters at the forefront of nanotechnology for biological and biomedical applications. To date, information on the interactions of gold nanoclusters with biological macromolecules is limited and restricts their use in living cells. Methods: Our multidisciplinary study begins to fill the current knowledge gap by focusing on lysosomes and associated biological pathways in U251N human glioblastoma cells. We concentrated on lysosomes, because they are the intracellular destination for many nanoparticles, regulate cellular homeostasis and control cell survival. Results: Quantitative data presented here show that gold nanoclusters (with 15 and 25 gold atoms), surface-modified with glutathione or PEG, did not diminish cell viability at concentrations ≤1 µM. However, even at sublethal concentrations, gold nanoclusters modulated the abundance, positioning, pH and enzymatic activities of lysosomes. Gold nanoclusters also affected other aspects of cellular homeostasis. Specifically, they stimulated the transient nuclear accumulation of TFEB and Nrf2, transcription factors that promote lysosome biogenesis and stress responses. Moreover, gold nanoclusters also altered the formation of protein aggregates in the cytoplasm. The cellular responses elicited by gold nanoclusters were largely reversible within a 24-hour period. Conclusions: Taken together, this study explores the subcellular and molecular effects induced by gold nanoclusters and shows their effectiveness to regulate lysosome biology. Our results indicate that gold nanoclusters cause homeostatic perturbations without marked cell loss. Notably, cells adapt to the challenge inflicted by gold nanoclusters. These new insights provide a framework for the further development of gold nanocluster-based applications in biological sciences.