Assessment of FDA-approved drugs against Strongyloides ratti in vitro and in vivo to identify potentially active drugs against strongyloidiasis

Background Infections with Strongyloides stercoralis belong to the most neglected helminth diseases, and research and development (R&D) efforts on novel drugs are inadequate. Methods A commercially available library containing 1600 FDA-approved drugs was tested in vitro against Strongyloides ratti larvae (L3) at 100 µM. Hits (activity > 70%) were then evaluated against S. ratti adult worms at 10 µM. Morantel, prasterone, and levamisole were tested in the S. ratti rat model using dosages of 1–100 mg/kg. Results Seventy-one of the 1600 compounds tested against S. ratti L3 revealed activity above 70%. Of 64 compounds which progressed into the adult screen, seven compounds achieved death of all worms (benzethonium chloride, cetylpyridinium chloride, Gentian violet, methylbenzethonium chloride, morantel citrate, ivermectin, coumaphos), and another eight compounds had activity > 70%. Excluding topical and toxic compounds, three drugs progressed into in vivo studies. Prasterone lacked activity in vivo, while treatment with 100 mg/kg morantel and levamisole cured all rats. The highest in vivo activity was observed with levamisole, yielding a median effective dose (ED50) of 1.1 mg/kg. Conclusions Using a drug repurposing approach, our study identified levamisole as a potential backup drug for strongyloidiasis. Levamisole should be evaluated in exploratory clinical trials. Graphical Abstract

Synthesis of Hexahydroxy Strontium Stannate/Tin Dioxide Nanocomposites and Their Photocatalytic Properties for Gentian Violet

Background: Gentian violet dye released from industries into the environment has caused serious water pollution and is a significant environment pollutant to human beings owing to the toxicity. It is urgent to decrease the environmental pollution by removing gentian violet in the wastewater. Objective: The aim is to synthesize hexahydroxy strontium stannate/tin dioxide nanocomposites by a simple hydrothermal method without surfactants and research the photocatalytic performance for gentian violet degradation. Methods: Hexahydroxy strontium stannate/tin dioxide nanocomposites have been obtained via the hydrothermal method. The structure, size, morphology and photocatalytic performance were characterized by X-ray diffraction, electron microscopy, solid ultraviolet-visible diffuse reflectance spectroscopy and X-ray photoelectron spectroscopy. Results : The nanocomposites possess oven-shaped morphology with the size of less than 100 nm and are composed of hexagonal SrSn(OH)6 and tetragonal SnO2 phases. The band gap of the nanocomposites is 3.52 eV. 10 mg hexahydroxy strontium stannate/tin dioxide nanocomposites have the ability to completely degrade 10 mL gentian violet solution with the concentration of 10 mgL-1 under 6 h ultraviolet-visible light irradiation. Hydroxyl radical, hole and superoxide radical are main species for the gentian violet photocatalytic degradation using the nanocomposites. Conclusion: The hexahydroxy strontium stannate/tin dioxide nanocomposites show good photocatalytic performance for the GV degradation. The photocatalytic performance for gentian violet degradation using the hexahydroxy strontium stannate/tin dioxide nanocomposites depends on the irradiation time and content of the nanocomposites.

Results 25 Years After Hemiarthroplasty for Chondrolysis of the Shoulder. A Report of Two Cases

Two patients (age, 34 and 52 years) underwent an open repair of concealed rotator cuff tear with the aid of color arthrography using gentian violet. Postoperatively, they developed chondrolysis of the shoulder, which was treated with hemiarthroplasty. Twenty-five years after hemiarthroplasty, both patients showed good shoulder function without significant glenoid erosion on radiographs. Satisfactory long-term results are most probably due to maintenance of humeral head centering and glenohumeral conformity. These are the longest follow-up cases of arthroplasty for chondrolysis of the shoulder in the literature. We conclude that hemiarthroplasty can be a reasonable option for patients with this unfortunate disorder.

Assessment of the Use of Gentian Violet and Malachite Green as Selective Agents in the Isolation of Brucella

The aim of the work is to evaluate ability of gentian violet and malachite green to inhibit 2 Brucella test strains and 8 strains of unwanted organisms and the influence of autoclaving on their activity. The study also aims to evaluate variability of inhibition in different batches of colorants and necessity in adjustment of their concentration.Materials and methods. The study included 3 imported lots of gentian violet and malachite green. Inhibitors were put into nutrient medium containing pancreatic hydrolysates of gelatin and fsh meal, yeast extract, sodium chloride, glucose, sodium pyrosulfate, and agar. The same medium without colorants was used as a control medium. Effect of the colorants was studied with the help of test strains of Brucella abortus 19 ВА, B. melitensis Rev I, Enterococcus faecium VKM B-602, Escherichia coli ATCC 25922, Proteus vulgaris HX 19 222, Pseudomonas aeruginosa 22/99, Serracia plymuthica 1, Shigella flexneri 1a 8516, Staphylococcus aureus ATCC 25923, Yersinia enterocolitica C-187.Results and discussion. We have determined biological parameters of nutrient media containing gentian violet (5,0; 2,5 1,25 mg/L) and malachite green (2.0; 1.0; 0.5 mg/L) when cultivating brucella. Gentian violet is able to inhibit Brucella greatly at concentration of 5 mg/L. S. aureus ATCC 25923 did not show any growth on the media containing malachite green or gential violet (5.0 and 2.5 mg/L). Malachite green inhibited the growth of enterococcus more actively than gentian violet. However, it inhibited swarming growth of Proteus less successfully than gentian violet. Other unwanted organisms were not sensitive to such concentrations of colorants at all. We have demonstrated the necessity to combine colorants with other selective agents, as well as advisability to put gentian violet into sterile media, while malachite green – into the media before its autoclaving. Adjustments to the concentration of gentian violet should be made when producing nutrient medium, as variations in inhibiting activity in different batches of this colorant were revealed.

Drug Repurposing for Alzheimer’s Disease Based on Protein-Protein Interaction Network

Alzheimer’s disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment are vital. This study proposes a method to extract substantial gene complexes and then introduces potential drugs in Alzheimer’s disease. To this end, a protein-protein interaction (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. An enrichment analysis to introduce the most important biological processes and pathways was accomplished on the obtained genes. The next step is extracting the drugs related to AD and introducing some new drugs which may be helpful for this disease. Finally, a complete network including all the genes associated with each gene complex group and genes’ target drug was illustrated. For validating the proposed potential drugs, Connectivity Map (CMAP) analysis was accomplished to determine target genes that are up- or downregulated by proposed drugs. Medical studies and publications were analyzed thoroughly to introduce AD-related drugs. This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. Raloxifene and gentian violet are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. Besides the primary goal, five bipartite networks representing the genes of each group and their target miRNAs were constructed to introduce target miRNAs.

Successful Management of Complex Pediatric and Neonatal Wounds With Methylene Blue and Gentian Violet Foam Dressings

Introduction. Topical antimicrobial treatment of wounds in pediatric, and especially neonatal, patients can be challenging due to increased systemic absorption, damaging inflammatory cytokines, and oxygen radicals released by bacterial death. A product combining all wound bed preparation principles is desired. Methylene blue and gentian violet (MB/GV) foam dressings can keep wound beds moist, decrease ongoing inflammation, provide antibacterial coverage, and promote healthy wound edges. Objective. This article examines the use of MB/GV antibacterial foams in pediatric patients. Cases included infants with giant omphalocele epidermal stripping, dehisced abdominal wounds, peristomal dermatitis, and peripheral intravenous extravasations and adolescents with stage 4 pressure injuries. The treatment goals were to optimize the wound bed through debridement, elimination of bioburden, providing moisture balance, and enhancement of granulation tissue growth. Materials and Methods. Eight patients (6 infants and 2 adolescents) received MB/GV foam dressings every 2 to 3 days along with standard of care (SOC) management. Results. Effective debridement, bioburden elimination, moisture balance, and edge enhancement were achieved in all wounds. All wound beds were well-prepared to receive other SOC products as needed. Three cases were considered for negative pressure wound therapy (NPWT), but NPWT was not used because of challenging clinical characteristics and wound locations. Instead, MB/GV polyvinyl alcohol foam provided capillary wicking action that enhanced wound closure without NPWT. No side effects were observed. Conclusions. Methylene blue and gentian violet foam dressings appear to be a safe clinical option for antibacterial coverage, moisture management, and debridement in neonatal and pediatric patients.

Cutaneous microbial biofilm formation as an underlying cause of red scrotum syndrome

Background Red scrotum syndrome is typically described as well-demarcated erythema of the anterior scrotum accompanied by persistent itching and burning. It is chronic and difficult to treat and contributes to significant psychological distress and reduction in quality of life. The medical literature surrounding the condition is sparse, with the prevalence likely under-recognized and the pathophysiology remaining poorly understood. Formation of a cutaneous microbial biofilm has not been proposed as an underlying etiology. Microbial biofilms can form whenever microorganisms are suspended in fluid on a surface for a prolonged time and are becoming increasingly recognized as important contributors to medical disease (e.g., chronic wounds). Case presentation A 26-year-old man abruptly developed well-demarcated erythema of the bilateral scrotum after vaginal secretions were left covering the scrotum overnight. For 14 months, the patient experienced daily scrotal itching and burning while seeking care from multiple physicians and attempting numerous failed therapies. He eventually obtained complete symptomatic relief with the twice daily application of 0.8% menthol powder. Findings in support of a cutaneous microbial biofilm as the underlying etiology include: (1) the condition began following a typical scenario that would facilitate biofilm formation; (2) the demarcation of erythema precisely follows the scrotal hairline, suggesting that hair follicles acted as scaffolding during biofilm formation; (3) despite resolution of symptoms, the scrotal erythema has persisted, unchanged in boundary 15 years after the condition began; and (4) the erythematous skin demonstrates prolonged retention of gentian violet dye in comparison with adjacent unaffected skin, suggesting the presence of dye-avid material on the skin surface. Conclusion The probability that microorganisms, under proper conditions, can form biofilm on intact skin is poorly recognized. This case presents a compelling argument for a cutaneous microbial biofilm as the underlying cause of red scrotum syndrome in one patient, and a review of similarities with other reported cases suggests the same etiology is likely responsible for a significant portion of the total disease burden. This etiology may also be a significant contributor to the disease burden of vulvodynia, a condition with many similarities to red scrotum syndrome.