A clinical mimicker of melanoma with distinctive histopathology: Topical silver nitrate exposure.

Exposure to silver-containing compounds can result in reversible discoloration of the skin, presenting as an irregular brown or black macule, which can have a clinical appearance similar to melanoma. Both the clinical scenario and the histopathology are unique. Silver nitrate darkens with exposure to light, and the area can appear to change over time. On microscopic examination, there are coarse pigmented granules dispersed throughout the corneal layer, and largely absent from the remainder of the epidermis-although the precise location may depend on the duration of topical exposure. While argyria, its irreversible counterpart, has been well-characterized, only a single source has previously reported the histopathology of transient topical silver nitrate exposure. We present two cases, review the clinical and histopathologic differentials, and detail the distinctive histopathology that enables a diagnosis to be suggested in this clinical mimicker of melanoma.

Interventions for preventing ophthalmia neonatorum.

BACKGROUND: Ophthalmia neonatorum is an infection of the eyes in newborns that can lead to blindness, particularly if the infection is caused by Neisseria gonorrhoeae. Antiseptic or antibiotic medication is dispensed into the eyes of newborns, or dispensed systemically, soon after delivery to prevent neonatal conjunctivitis and potential vision impairment. OBJECTIVES: 1. To determine if any type of systemic or topical eye medication is better than placebo or no prophylaxis in preventing ophthalmia neonatorum. 2. To determine if any one systemic or topical eye medication is better than any other medication in preventing ophthalmia neonatorum. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers, date of last search 4 October 2019. We also searched references of included studies and contacted pharmaceutical companies.  SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials of any topical, systemic, or combination medical interventions used to prevent ophthalmia neonatorum in newborns compared with placebo, no prophylaxis, or with each other. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Outcomes were: blindness or any adverse visual outcome at 12 months, conjunctivitis at 1 month (gonococcal (GC), chlamydial (CC), bacterial (BC), any aetiology (ACAE), or unknown aetiology (CUE)), and adverse effects.  MAIN RESULTS: We included 30 trials with a total of 79,198 neonates. Eighteen studies were conducted in high-income settings (the USA, Europe, Israel, Canada), and 12 were conducted in low- and middle-income settings (Africa, Iran, China, Indonesia, Mexico). Fifteen of the 30 studies were quasi-randomised. We judged every study to be at high risk of bias in at least one domain. Ten studies included a comparison arm with no prophylaxis. There were 14 different prophylactic regimens and 12 different medications in the 30 included studies. Any prophylaxis compared to no prophylaxis  Unless otherwise indicated, the following evidence comes from studies assessing one or more of the following interventions: tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%. None of the studies reported data on the primary outcomes: blindness or any adverse visual outcome at any time point. There was only very low-certainty evidence on the risk of GC with prophylaxis (4/5340 newborns) compared to no prophylaxis (5/2889) at one month (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.24 to 2.65, 3 studies). Low-certainty evidence suggested there may be little or no difference in effect on CC (RR 0.96, 95% CI 0.57 to 1.61, 4874 newborns, 2 studies) and BC (RR 0.84, 95% CI 0.37 to 1.93, 3685 newborns, 2 studies). Moderate-certainty evidence suggested a probable reduction in risk of ACAE at one month (RR 0.65, 95% 0.54 to 0.78, 9666 newborns, 8 studies assessing tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%, colostrum, bacitracin-phenacaine ointment). There was only very low-certainty evidence on CUE  (RR 1.75, 95% CI 0.37 to 8.28, 330 newborns, 1 study). Very low-certainty evidence on adverse effects suggested no increased nasolacrimal duct obstruction (RR 0.93, 95% CI 0.68 to 1.28, 404 newborns, 1 study of erythromycin 0.5% and silver nitrate 1%) and no increased keratitis (single study of 40 newborns assessing silver nitrate 1% with no events).    Any prophylaxis compared to another prophylaxis Overall, evidence comparing different interventions did not suggest any consistently superior intervention. However, most of this evidence was of low-certainty and was extremely limited. AUTHORS' CONCLUSIONS: There are no data on whether prophylaxis for ophthalmia neonatorum prevents serious outcomes such as blindness or any adverse visual outcome. Moderate-certainty evidence suggests that the use of prophylaxis may lead to a reduction in the incidence of ACAE in newborns but the evidence for effect on GC, CC or BC was less certain. Comparison of individual interventions did not suggest any consistently superior intervention, but data were limited. A trial comparing tetracycline, povidone-iodine (single administration), and chloramphenicol for GC and CC could potentially provide the community with an effective, universally applicable prophylaxis against ophthalmia neonatorum.

Use of Silver Nitrate Application as Mini-Invasive Treatment of Pilonidal Sinus Disease.

OBJECTIVES: To investigate the cure rate and adverse effects of silver nitrate application for treatment of pilonidal sinus disease (PSD). Methods: Number of sinus pit orifices, and complications with silver nitrate application and debridement for sacrococcygeal PSD between January 2015 and July 2018 were analyzed in this retrospective study. Data were obtained from surgical, discharge, and outpatient follow-up records. Among 56 patients who were treated with silver nitrate stick, 11 patients with incomplete hospital records were excluded from the study. Demographic data including age, gender, length of follow-up, number of silver nitrate applications, number of involved sinuses and recurrence and complication rates were recorded. Results were expressed as frequencies, means, and range of values. The Mann Whitney U and chi square tests were used to evaluate significance. Results: Mean age was 24.3 +- 5.18 (range, 14 - 36) years, and recurrence occurred in 4 (8.9%) patients. Complications developed in 10 (22.2%) patients and included abscess, erythema, and necrosis in 5 (11.1%), 2 (4.4%), and 3 (6.6%) patients, respectively. The recurrence rate was significantly higher in patients who developed abscesses during the follow-up period (p = 0.001) than those who did not. There was no statistically significant correlation between the recurrence rate and number of sinuses or the number of silver nitrate applications. CONCLUSION: Low morbidity and high healing rates achieved with silver nitrate provide support for this application as a feasible and effective conservative outpatient treatment for PSD in certain patients.

Comparative analysis of B-BOX genes and their expression pattern analysis under various treatments in Dendrobium officinale.

BACKGROUND: Studies have demonstrated that BBX (B-BOX) genes play crucial roles in regulatory networks controlling plant growth, developmental processes and stress response. Nevertheless, comprehensive study of BBX genes in orchids (Orchidaceae) is not well studied. The newly released genome sequences of Dendrobium officinale and Phalaenopsis equestris have allowed a systematic analysis of these important BBX genes in orchids. RESULTS: Here we identified 19 (DoBBX01-19) and 16 (PeBBX01-16) BBX genes from D. officinale and P. equestris, respectively, and clustered into five clades (I-V) according to phylogenetic analysis. Thirteen orthologous, two DoBBXs paralogous and two PeBBXs paralogous gene pairs were validated. This gene family mainly underwent purifying selection, but five domains experienced positive selection during evolution. Noteworthy, the expression patterns of root, root_tips, stem, leaf, speal, column, lip, and flower_buds revealed that they might contribution to the formation of these tissues. According to the cis-regulatory elements analysis of BBX genes, qRT-PCR experiments were carried out using D. officinale PLBs (protocorm-like bodies) and displayed that these BBX genes were differentially regulated under AgNO3, MeJA (Methyl Jasmonate), ABA (abscisic acid) and SA (salicylic acid) treatments. CONCLUSIONS: Our analysis exposed that DoBBX genes play significant roles in plant growth and development, and response to different environmental stress conditions of D. officinale, which provide aid in the selection of appropriate candidate genes for further functional characterization of BBX genes in plants.

Pleurodesis.

Symptomatic pleural disease, specifically malignant pleural effusion, refractory benign pleural effusion, and pneumothoraces are common diseases that often require therapeutic interventions. The spectrum of management strategies often includes selection of a chemical pleurodesis agent administered in combination with an indwelling pleural catheter or chest tube.Additionally, there is a role for minimally invasive techniques which include medical thoracoscopy or more advanced video-assisted thoracoscopic approaches. Ongoing clinical trials continue to evolve best practices regarding the optimal sclerosant agents and procedural approaches in the management of these diseases.

Combination of sulfonamides, silver antimicrobial agents and quorum sensing inhibitors as a preferred approach for improving antimicrobial efficacy against Bacillus subtilis.

More and more antibacterial agents are used together to treat bacterial infections in diverse fields, but the overuse of antibacterial agents may cause the environmental pollution of antibiotic resistance genes (ARGs). In order to reduce the use of antimicrobial agents, the potential joint effects of quorum-sensing inhibitors (QSIs) and traditional antimicrobial agents have been proposed to be effective. In this study, the joint effects of traditional antimicrobial agents, represented by sulfonamides (SAs) and silver antibacterial agents (silver nitrate (AgNO3) and nanosilver (AgNP, 5 nm)), and five potential QSIs, were investigated using B. subtilis. It was found that AgNP showed higher toxicity than AgNO3, whereas the joint effects on B. subtilis showed no difference between AgNO3 and AgNP when they combined with SAs or QSIs, respectively. In general, AgNO3 and AgNP presented synergetic and additive effects with QSIs, but additive and antagonistic effects with SAs; SAs exhibited synergetic, additive and antagonistic effects with different QSIs whether in binary or ternary mixed system. Moreover, it was found that the use of antimicrobials was reduced and the synergistic combined toxicity of antimicrobial agents on B. subtilis was increased through the addition of the QSIs. This study can offer a valuable reference for the combined medication of the different antimicrobial agents, which will benefit the environmental and human health.

Reproducibility of the effects of homeopathically potentised Argentum nitricum on the growth of Lemna gibba L. in a randomised and blinded bioassay.

BACKGROUND: A previous study reported a significant statistical interaction between experiment date and treatment effect of Argentum nitricum 14x-30x on the growth rate of duckweed (Lemna gibba L.). The aim of the present study was to investigate the stability of the test system and intra-laboratory reproducibility of the effects found. METHODS: Duckweed was treated with A. nitricum potencies (14x-30x) as well as succussed and unsuccussed water controls. The outcome parameter area-related growth rate for day 0-7 was determined by a computerised image analysis system in two series of independent randomised and blinded experiments. Systematic negative control (SNC) experiments were carried out to investigate test system stability. Statistical analysis was performed with full two-way analysis of variance (ANOVA) and protected Fisher's Least Significant Difference (LSD) test. RESULTS: In the first repetition series we found a significant treatment effect (p = 0.016), while in the second series no effect was observed. The negative control experiments showed that the experimental system was stable. An a posteriori subgroup analysis concerning gibbosity revealed the importance of this growth state of L. gibba for successful reproduction of the statistically significant interaction in the original study; flat: no interaction (p = 0.762); slight gibbosity: no interaction (p = 0.356); medium gibbosity: significant interaction (p = 0.031), high gibbosity: highly significant interaction (p = 0.005). CONCLUSIONS: With the original study design (disregarding gibbosity status of L. gibba) results of the original study could not be reproduced sensu stricto. We conclude that the growth state gibbosity is crucial for successful reproduction of the original study. Different physiological states of the test organisms used for bioassays for homeopathic basic research must carefully be considered.

Brain-targeted distribution and high retention of silver by chronic intranasal instillation of silver nanoparticles and ions in Sprague-Dawley rats.

The wide applications of silver nanoparticles (AgNPs) have been concerned regarding their unintentional toxicities. Different exposure modes may cause distinct accumulation, retention and elimination profiles, which are closely related with their toxicities. Unlike silver accumulation profiles through other regular administration modes, the biodistribution, accumulation and elimination of AgNPs by intranasal instillation are not fully understood. This study conducted intranasal instillation of polyvinylpyrrolidone-coated AgNPs in neonatal Sprague-Dawley rats at doses of 1 and 0.1 mg kg(-1) day(-1) for 4 and 12 weeks, respectively. The 4-week recovery was also designed after the 12-week exposure. Silver concentrations in the main tissues or organs were periodically monitored. Parallel exposures using silver ion were performed for the comparative studies. No physiological alterations were observed in AgNP exposures. In comparison, 1 mg kg(-1) day(-1) silver ions decreased body weight gain and caused mortality of 18.2%, showing ionic silver had a relatively higher toxicity than AgNPs. A relatively higher silver accumulation was observed in silver ion groups than AgNP groups. The silver ion release could not fully explain silver accumulation in AgNP exposures, showing silver distribution caused by particulate silver occurred in vivo. The highest silver concentration was in the liver at week 4, while it shifted to the brain after a 12-week exposure. Dose-related silver accumulation occurred for both AgNP and silver ion groups. The time course revealed a uniquely high concentration and retention of brain silver, implying chronic intranasal instillation caused brain-targeted silver accumulation. These findings provided substantial evidence on the potential neuronal threat from the intranasal administration of AgNPs or silver colloid-based products.

Long-term kinetics of AA amyloidosis and effects of inflammatory restimulation after disappearance of amyloid depositions in mice.

Amyloid A (AA) amyloidosis is characterized by extracellular pathogenic deposition of insoluble fibril protein in various body organs. Deposited amyloid generally remains in a variety of organs for long periods, but its disappearance has been reported after the precursor protein is diminished. The kinetics of AA deposition are not completely understood and, in particular, the roles of cells and cytokines in the deposition and clearance of amyloid remain unclear. In this study, we investigated the disappearance of amyloid depositions in mice over a 1-year period. AA amyloidosis was induced experimentally in mice by injecting amyloid-enhancing factor (AEF) and silver nitrate. Mice were killed at different time-points to examine the occurrence and disappearance of amyloid depositions. Maximum levels of amyloid depositions were observed at 20 days after inoculation. Clearance of amyloid depositions was observed from the 40th day onwards, with only minute traces of amyloid present by 240 days. A second inflammatory stimulus consisting of AEF and silver nitrate was given at 330 or 430 days, after amyloid depositions had disappeared almost completely. After that, serum amyloid A was overproduced and redeposition of amyloid was observed, indicating that all mice were primed for aggressive amyloid depositions. After administration of the inflammatory stimuli, the proinflammatory environment was found to have increased levels of interleukin (IL)-6, while anti-inflammatory conditions were established by IL-10 as regression of amyloid deposition occurred. These results suggest that the proinflammatory and anti-inflammatory status have key roles in both amyloid deposition and clearance.

Safety and systemic consequences of pleurodesis with three different doses of silver nitrate in patients with malignant pleural effusion.

BACKGROUND: Silver nitrate (SN) is an alternative to talc pleurodesis in patients with malignant pleural effusion (MPE). Nevertheless, SN complications have not been thoroughly investigated so far. OBJECTIVE: To evaluate frequent adverse events (AE) of SN treatment at three different doses for pleurodesis in patients with MPE. The secondary objective was to evaluate systemic inflammation, efficacy and quality of life in these patients. METHODS: A double-blind, randomized, clinical trial was conducted in patients with recurrent MPE at a tertiary university hospital. The study patients underwent pleural catheter insertion and were randomly assigned to one of the three pleurodesis groups treated with 30 ml 0.3%, 30 ml 0.5% or 60 ml 0.3% SN. Patients were discharged 3 days after the procedure, and returned to follow-up visits on days 10 and 30. During follow-up, AE, inflammatory markers, quality of life and CT scans were systematically assessed and documented. RESULTS: Sixty patients (11 males and 49 females, median age 62.13 years) were included. Overall, 199 AE were observed, including 23 serious AE. Grade 1/2 metabolic AE, such as increases in creatinine and liver enzymes, were the most frequent. Grade 3/4 hypoxia was observed in 13 patients. Four patients died, 3 due to disease progression and in 1 patient death was possibly related to pleurodesis. C-reactive protein levels increased in a dose-dependent manner and peaked 48 h after pleurodesis. No significant difference was observed among groups regarding quality of life or clinical/radiological recurrence. CONCLUSION: Hypoxia was the most significant AE following SN pleurodesis; mild metabolic events were very common. SN instillation causes substantial dose-dependent systemic inflammatory responses.

Topical antimicrobial photodynamic therapy improves angiogenesis in wounds of diabetic mice.

We report the results of our investigations on the effect of antimicrobial photodynamic therapy (APDT) on angiogenesis in wounds of diabetic mice. For this, measurements were made on levels of nitric oxide (NO), vascular endothelial growth factor-A (VEGF-A), and markers of proinflammatory stress (phosphorylated nuclear factor kappa B and p(38) mitogen-activated protein kinase) on day 3 post-wounding. For uninfected and infected wounds, the levels of NO, VEGF-A were lower and the levels of phospho-NF-kB-p65, phospho-p(38)MAPK were higher in diabetic mice compared with that in nondiabetic mice. For infected wounds, multiple APDT (fluence ~60 J/cm(2)) led to increase in NO, VEGF-A levels and a decrease in the phospho-NF-kB-p65, phospho-p(38)MAPK. Further, compared with aminoguanidine, and silver nitrate, multiple APDT was observed to result in a much improved proangiogenic response.

Wheat and ultra high diluted silver nitrate--further experiments and re-analysis of data.

BACKGROUND: Since 1926, an influence of a dilution of silver nitrate (24x) on the growth of coleoptiles of wheat seedlings was described. The aim of the study discussed here is the critical proof of the reliability of a test system which has been quoted as a basic model for the research on homoeopathy for decades. METHODS: Grains of winter wheat (Triticum aestivum) were observed under the influence of extremely diluted silver nitrate (10(-23)) prepared by stepwise dilution and agitation according to a protocol derived from homeopathy ('24x'). Analogously prepared water and/or inert water was used for control. Thirty experiments including 5000+5000 grains were performed by 5 researchers. RESULTS: Stalk lengths clearly indicate that development is enhanced by the probe silver nitrate 24x as compared to control. When the experiments 1989-1995 were pooled, means and SD for silver nitrate 24x-groups were 42.3±26.9 mm and for water control groups 34.7±22.2 mm. Verum stalk length was 21.9% bigger than control (100%) (p<0.01; d=0.31, i.e. small). For the experiments 1998-2014, means and SD were 73.7±21.7 mm and 60.5±20.9 mm. Verum stalk length was 21.7% bigger than control (100%) (p<0.01; d=0.62, i.e. medium). From the results one may hypothesize that the result is more marked in experiments showing an average mean of stalk length between ca. 50 and 90 mm in contrast to smaller or bigger mean lengths. CONCLUSION: The previous findings were confirmed by the results.

Toxic effects of repeated oral exposure of silver nanoparticles on small intestine mucosa of mice.

As the use of silver nanoparticles (AgNPs) is increasing fast in industry, food, medicines, etc., exposure to AgNPs is increasing in quantity day by day. So, it is imperative to know the adverse effects of AgNPs in man. In this study, we selected mice as an animal model and observed the effect of AgNPs on small intestinal mucosa. AgNPs ranging from 3 to 20 nm were administered orally at a dose of 5, 10, 15 and 20 mg/kg body weight to the Swiss-albino male mice for 21 d. There was a significant decrease (p < 0.05) in the body weight of mice in all the AgNPs-treated groups. Mice treated at a dose of 10 mg/kg showed the maximum weight loss. Effects were noted by using light microscopy as well as transmission electron microscopy. It was found that AgNPs damage the epithelial cell microvilli as well as intestinal glands. It may be hypothesized that loss of microvilli reduced absorptive capacity of intestinal epithelium and hence weight loss.

Management of bilateral idiopathic renal hematuria in a dog with silver nitrate.

Renal hematuria has limited treatment options. This report describes management of bilateral idiopathic renal hematuria in a dog with surgically assisted installation of 0.5% silver nitrate solution. Initial treatment resulted in freedom from clinical signs or recurrent anemia for 10 months; however, recurrence of bleeding following a nephrectomy resulted in euthanasia.

Gestion de l'hématurie rénale idiopathique bilatérale chez un chien à l'aide du nitrate d'argent. L'hématurie rénale offre des options de traitement limitées. Ce rapport décrit la gestion de l'hématurie rénale idiopathique bilatérale chez un chien à l'aide de l'installation assistée par chirurgie d'une solution de nitrate d'argent de 0,5 %. Le traitement initial a produit une disparition des signes cliniques ou de l'anémie récurrente pendant 10 mois. Cependant, la récurrence des saignements après une néphrectomie se sont traduits par l'euthanasie.(Traduit par Isabelle Vallières).

Use of a drug eluting pleural catheter for pleurodesis.

PURPOSE: Repeated administration of low-dose silver nitrate (SN) has been shown to be effective in creating pleurodesis. This study aimed to determine the effectiveness of a SN-eluting pleural catheter for pleurodesis. METHODS: Catheters with a chitosan-SN-hyaluronic acid hydrogel coating designed to release SN over 14 days, or placebo uncoated catheters, were inserted in rabbit and lamb pleurodesis models. Pleurodesis was assessed at 28 days according to a 1-8 point scoring system and pleural fibrosis and inflammation assessed histologically on a 0-4 point scale. RESULTS: In the rabbit model, pleurodesis scores were significantly increased in both the 24 mg and 50 mg SN catheters versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 5, 8, and 1, respectively, median score for contralateral side was 1 in all groups). In the lamb model, pleurodesis scores were significantly increased in both the 750 mg and 1000 mg catheter groups versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 7, 7, and 1, respectively, median score for contralateral pleural space was 1 in all groups). Catheters appeared well tolerated, although higher than expected mortality was seen in the 50 mg catheter rabbit group. CONCLUSIONS: A catheter designed to deliver SN to the pleural space over 14 days appears to be effective in creating pleurodesis. Further investigations to determine in-vivo catheter pharmacokinetics, toxicity, dose and optimal coating methods are warranted.

Single step preparation of nanosilver loaded calcium phosphate by low temperature co-conversion process.

The preparation and characterization of nanosilver loaded calcium phosphate aiming to enhance the bactericidal performance by a single step co-conversion technique using low temperature ion exchange phosphorization in combination with Tollen's reaction were performed. Silver nitrate was used as a silver ion supply source (0.001-0.1 M) and glucose was employed as a reducing agent. After conversion, surface and shell zones of all samples comprised hydroxyapatite and metallic silver as the main phases regardless of silver nitrate concentration. However, hydroxyapatite, residual calcium sulfate and monetite were found in the core zone when using silver nitrate concentration lower than 0.1 M. The microstructure of all samples comprised the distribution of spherical-shaped silver nanoparticles within the cluster of calcium phosphate nanocrystals. Total silver content (range, 0.09-6.5 %) in the converted samples was found to linearly increase with increasing silver nitrate content. Flexural modulus and strength of converted samples generally decreased with increasing silver content. Effective antibacterial activity of two selected samples (0.001 and 0.005 M AgNO(3)) against two bacterial strains (Pseudomonas aeruginosa and Staphylococcus aureus) was observed. Cytotoxic potentials by MTT assay of both samples were observed at 24 and 48 h extraction respectively.

Back to the future: the medical management of caries introduction.

Based on the literature, a protocol was developed involving the application of 25 percent silver nitrate directly to cavitated caries lesions, immediately followed by 5 percent sodium fluoride varnish. This protocol results in arrest of active caries lesions. This minimally invasive treatment is well-accepted by patients and reduces anxieties related to dental office visits.