Virulence profile of Candida spp. isolated from an anaerobic biodigester supplied with dairy cattle waste.

Anaerobic biodigesters play a crucial role in enhancing animal waste management. However, the presence of pathogens in the biodigestion process poses a significant concern. Candida spp., a widespread fungus known for its opportunistic nature and adaptability to diverse environmental conditions, including reciprocal transmission between humans and animals, is one such pathogen of concern. Therefore, it is imperative to assess the virulence profile of Candida spp. originating from anaerobic biodigestion processes. Here we demonstrate that strains isolated from the biodigestion process of dairy cattle waste exhibit noteworthy virulence mechanisms, surpassing the virulence of clinical control strains. After we identified strains from affluent, effluent, and biofertilizer, we observed that all analyzed isolates produced biofilm. Additionally, a substantial proportion of these isolates demonstrated phospholipase production, while only a few strains exhibited protease production. Furthermore, all strains exhibited resistance or dose-dependent responses to amphotericin B and itraconazole, with the majority displaying resistance to fluconazole. In the in vivo test, we observed a significant correlation (p < 0.05) between the LT50 and biofilm formation as well as hyphae/pseudohyphae production. Additionally, some isolates demonstrated a quicker nematode-killing capacity compared to clinical controls. Our findings underscore the considerable pathogenic potential of certain Candida species present in the dynamics of anaerobic biodigestion. Importantly, the anaerobic biodigester system did not eliminate Candida strains from dairy cattle waste, highlighting the need for caution in utilizing biodigester products. We advocate for further studies to explore the virulence of other microorganisms in various animal production contexts. Furthermore, our results emphasize the urgency of enhancing waste treatment methods to effectively eliminate pathogens and curb their potential dissemination.

Amphotericin B-loaded natural latex dressing for treating Candida albicans wound infections using Galleria mellonella model.

Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL-1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL-1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.

Initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin.

BACKGROUND: Calvaria skin has a reduced thickness, and its initial damage produced by irradiation was scarcely reported. We aimed to identify the initial effects of x-ray irradiation in the rat calvaria skin. METHODS: After approval by the Animal Ethical Committee, calvaria skin sections of five Wistar rats per time point were evaluated on days 4, 9, 14, and 25 following a single 15-Gy x-ray irradiation of the head. The control group was composed of five rats and evaluated on day 4. Sections were assessed using hematoxylin-eosin and Masson's trichrome staining for morphology, inflammation, and fibrosis. Fibrosis was also evaluated by the collagen maturation index from Picrosirius red staining and by cell proliferation using the immunohistochemistry, after 5-bromo-2-deoxyuridine intraperitoneal injection. RESULTS: In irradiated rats, we observed a reduction in epithelial cell proliferation (p = 0.004) and in matrix metalloproteinase-9 expression (p < 0.001), an increase in the maturation index, and with a predominance in the type I collagen fibers, on days 9 and 14 (1.19 and 1.17, respectively). A progressive disorganization in the morphology of the collagen fibers at all time points and changes in morphology of the sebaceous gland cells and hair follicle were present until day 14. CONCLUSIONS: The initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin was a change in the normal morphology of collagen fibers to an amorphous aspect, a temporary absence of the sebaceous gland and hair follicles, and without a visible inflammatory process, cell proliferation, or fibrosis process in the dermis.

Expression of the matrix metalloproteinases 2 and 9 in the rat small intestine during intrauterine and postnatal life.

The expressions of matrix metalloproteinases 2 and 9 have been described during the development, as an example in heart and tooth but not in the small intestine yet. In this context, this study aimed to evaluate the expressions of MMP-2 and MMP-9 in the small intestine of Wistar rats during intrauterine (IU) and postnatal (PN) life. Expressions were determined on the 15th and 18th days of IU life and the 3rd, 10th, 17th, 25th, and 32nd days of PN life. Intestinal samples obtained from six animals were submitted to zymography, immunohistochemistry, and staining with Masson's trichrome. The results showed that MMP-2 and MMP-9 were not expressed during IU life; however, after birth, MMP-9 was immunolocalized in the goblet and mast cells. In conclusion, our results showed that MMP-2 and MMP-9 were not expressed in absorptive epithelial cells during the IU period of the small intestine but after birth, MMP-9 was expressed in the goblet cells, and mast cells present in the lamina propria.

Safety of Treatments for ADHD in Adults: Pairwise and Network Meta-Analyses.

OBJECTIVE: The aim of the study was to analyze evidence comparing the profile of drugs used to treat ADHD in adult patients. METHOD: Systematic searches were conducted in electronic databases. Randomized, double-blind, parallel controlled trials that evaluated the safety of drugs in ADHD were included. The statistical analyses were conducted by pairwise meta-analyses and mixed treatment comparison (MTC). RESULTS: Ten ( n = 3006) trials were included in the analyses. We observed statistical differences for the following outcomes: decreased appetite between atomoxetine and placebo (odds ratio [OR] = 0.15, 95% credibility interval [CrI] = [0.05, 0.38]) and extended-release mixed amphetamine salts and placebo (OR = 0.06, 95% CrI = [0.00, 0.51]); insomnia between atomoxetine and placebo (OR = 0.48, 95% CrI = [0.27, 0.88]) and extended-release mixed amphetamine salts and placebo (OR = 0.23, 95% CrI = [0.06, 0.76]); sleepiness between atomoxetine and methylphenidate OROS (OR = 0.24, 95% CrI = [0.06, 0.97]); and decreased libido between atomoxetine and placebo (OR = 0.28, 95% CrI = [0.08, 0.90]). CONCLUSION: It was possible to generate evidence about the safety profile of different ADHD drugs.

Light-stick: A problem of marine pollution in Brazil.

Light-sticks are used as bait in surface long-line fishing, to capture swordfish and other large pelagic predators. When discharged in the ocean, it may reach the beaches. The traditional Brazilian community of Costa dos Coqueiros, Bahia, use light-sticks as a medicine for rheumatism, vitiligo and mycoses. It may affect the marine life when its content leak in the open ocean. This work evaluated and identified the acute and chronic toxicity of the light-stick. A high acute toxicity was observed in the mobility/mortality of Artemia sp.; in the fertilization of sea urchin eggs, and a high chronic toxicity in the development of the pluteus larvae of the same sea urchin. The main compounds that probably caused toxicity were the volatiles such as the fluorescent PAH and oxidants such as the hydrogen peroxide. Its disposal in the open ocean is a potential threat for marine life.

Goblet cells and intestinal Alkaline phosphatase expression (IAP) during the development of the rat small intestine.

This study aimed to evaluate the temporal and spacial distribution of the mucins produced by goblet cells and intestinal alkaline phosphatase (IAP) expression during the development of the small intestine of the rat. Intestines were removed from rats on the 15th, 17th and 18th days of intratuterine life (i.u.) and on the 3rd, 10th, 17th and 25th days after birth (a.b.). Intestines were processed for routine histological procedures and sections were submitted to histochemistry using PAS to stain neutral glycoproteins and Alcian blue for acidic glycoproteins, as well as immunohistochemistry to detect IAP. In rats, glycoprotein production was seen to begin in the intestinal epithelium cell at around the 17th day of i.u. life; however, this production was not accompanied by morphological indications of the presence of goblet cells. By the 18th i.u. day, the villus epithelium was undergoing differentiation and the first goblet cells could be identified from this time. At around the 10th day a.b., both compartments of the small intestine were detected; i.e. the villi and the crypts. At this timepoint, goblet cells were present in the villi, and also in the upper regions of the crypts. On the 3rd, 10th 17th and 25th days a.b., the presence of the goblet cells increased and presented regional differences in the sections evaluated. IAP was not detected during i.u. life, but was weakly detected in the cells of the villi from the 3rd day a.b., along the entire extension of the villi. On the 10th day, IAP was detected at the tip of the villi, while on the 25th day, it was detected along the extension of the villi, but with a weaker intensity. In conclusion, a temporal and spacial distribution of goblet cells and IAP activity occurs during the development of the small intestine, suggesting a possible regulatory control in accordance with the suckling and weaning phases of food intake in the rat's life.

Biosimilar medicines - Review.

INTRODUCTION: By definition, biosimilars are similar to a biological reference that has already received marketing authorization for biologic drugs.The purpose of biosimilars is reducing costs, thus increasing access to this treatment, however, the concerns of health professionals and users refer to the fact that to reduce costs will not neglecting the quality, effectiveness and especially security. OBJECTIVE: The aim of this study is then to assess the degree of similarity between the biosimilar and its reference biopharmaceuticals, trying to understand the production process, requirements necessary for approval, and its impact on the quality, safety, efficacy and costs. METHODS: For the systematic review without meta-analysis, we researched articles to the b-on, Pubmed and Medscape to 2005-2014, and selected 23 articles that contributed to the verification of the objectives of this study. RESULTS: Several studies indicate that overall the biosimilar and biological reference showed no significant differences except those inherent to the production process, being the first susceptible to comparability tests demonstrating the similarity in terms of clinical efficacy and safety. CONCLUSION: Biosimilars will be increasingly present in the future as promising therapeutic arsenal and targeted therapy, however, issues related to immunogenicity, interchangeability, automatic substitution and extrapolation of indications should continue to be studied and debated.

The in vivo activity of 1,3,4-thiadiazolium-2-aminide compounds in the treatment of cutaneous and visceral leishmaniasis.

OBJECTIVES: Researchers have recently investigated the biological activities of mesoionic (MI) compounds, which have shown in vitro activity against many species of Leishmania, as well as Trypanosoma cruzi. The main goal of this study was to evaluate and compare the activity of three MI compounds against Leishmania amazonensis and Leishmania infantum infection in vivo. METHODS: The experiments were carried out using BALB/c mice infected with L. amazonensis or L. infantum as a highly sensitive murine model. The infected mice were treated with MI-HH, MI-4-OCH(3), MI-4-NO(2) or meglumine antimoniate by different routes (intralesional, topical or intraperitoneal). RESULTS: Treatment with MI-4-OCH(3) and MI-4-NO(2) efficiently contained the progression of cutaneous and visceral leishmaniasis in comparison with the control group or mice treated with meglumine antimoniate. Interestingly, these MI compounds did not produce toxicological effects after treatment. Furthermore, treatment with these compounds led to a modulation of the immune response that was correlated with disease control. In this study, MI compounds, and MI-4-NO(2) in particular, exhibited high activity in the L. infantum murine model. In the L. amazonensis model, intralesional treatment with MI-4-OCH(3) or MI-4-NO(2) showed greater therapeutic efficacy than treatment with meglumine antimoniate, and the new topical formulations of these compounds also displayed great activity in the cutaneous leishmaniasis model. CONCLUSIONS: Upon comparison of each MI compound, MI-4-NO(2) was clearly the compound with the greatest activity in these two in vivo infection models by each administration route tested.