Seasonal and circadian variation of non-volatile metabolites in Lippia alba leaves.

The present study describes the seasonal and circadian variations of the major compounds from Lippia alba leaves. SPSS was used to identify, quantify, and associate the variations in the secondary metabolites of this species through HPLC/DAD analysis of the leaves hydroethanolic extracts of six selected L. alba specimens. For the circadian study, the samples were collected at four different daily hours in each year's season. For the seasonal study, the samples were collected monthly from the same individuals for two consecutive years (2018 and 2019). These samples were analyzed and quantified using a validated HPLC method for flavonoids, iridoids, and phenyl ethanoid glycoside. Mussaenoside, acteoside, and tricin-7-O-diglucuronide showed a moderate positive correlation between their biosynthesis and the precipitation index, while epi-loganin had a moderate negative correlation. Acteoside showed a moderate positive correlation between the minimum registered temperature and its production. Compared with previous studies, a drastic reduction (about 95%) in the production of tricin-7-O-diglucuronide compared with previous study and this difference could be attributed to the plant's aging. Thus, the data demonstrated that lower temperatures and high rainfall could favor the production of the major L. alba active compounds (acteoside and tricin-7-O-diglucuronide) and that older plants harm their production.

Emergence of zoonotic sporotrichosis in Brazil: a genomic epidemiology study.

BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil.

Bimodal distribution of azole susceptibility in Sporothrix brasiliensis isolates in Brazil.

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.

Candida auris detected in the oral cavity of a dog in Kansas.

Candida auris is an emerging human fungal pathogen, first described in Japan in 2009, and first detected in the United States in 2016. Here, we report the first-ever description of C. auris colonizing a human pet, the first identification of C. auris in a non-human mammal in the United States and the first C. auris isolate from the state of Kansas. While analyzing the oral mycobiome of dogs from a shelter in Kansas, the oral swab from one dog was found to contain C. auris as well as three other fungal species. The presence of C. auris in a dog suggests the possibility of zoonotic transmission to humans. The isolate is a member of Clade IV, which has been found in patients in Chicago and Florida, while Clades I and III are the most prevalent in the United States. The isolate is resistant to fluconazole, terbinafine, and amphotericin B but susceptible to caspofungin, consistent with the drug-resistant characteristics of many human C. auris isolates. The source of C. auris transient colonization in this dog is unknown, and there is no evidence that it was further transmitted to humans, other dogs in the shelter, or pets in its adopted household. Isolation of C. auris from a dog in Kansas has public health implications as a potential emerging source for the zoonotic spread of this pathogenic fungus, and for the development of antifungal resistance.IMPORTANCECandida auris is an emerging fungal infection of humans and is particularly problematic because it is multi-drug resistant and difficult to treat. It is also known to be spread from person to person by contact and can remain on surfaces for long periods of time. In this report, a dog in a shelter in Kansas is found to be colonized with Candida auris. This is the first study to document the presence of Candida auris on a pet, the first to document C. auris presence on a non-human mammal in the United States, and the first to report an isolate of C. auris within the state of Kansas. The presence of C. auris in a pet dog raises the possibility of zoonotic transmission from pets to human or vice versa.

Screen time is negatively associated with sleep quality and duration only in insufficiently active adolescents: A Brazilian cross-sectional school-based study.

Background: Time spent on screen devices affects sleep quality and duration leading to several health impairments in youth. Although physical activity (PA) benefits sleep patterns and decreases screen time in adolescents, it is unclear whether the relationship between sleep quality/duration and screen time could be influenced by PA levels. Objective: To analyze the association between sleep quality and duration with screen time in Brazilian adolescents according PA levels. Methods: The sample included 1010 adolescents aged 13.2 ± 2.4 years (n = 556 females - 55 % of the sample). Sleep quality and sleep duration, and PA were assessed by Mini Sleep and Baecke questionnaires, respectively. Participants in the highest quartile were classified as physically active. Screen time was analyzed by the self-reported number of hours spent on different screen devices (i.e., television, computer, videogame, and cellphone/tablet). Participants in the highest tertile were classified as having high screen time. Sex, age, and body mass index were considered covariates in binary logistic regression models. Results: Poor sleep quality was observed in 52.3 % of the sample, whereas 46.6 % reported sleeping less than eight hours/day. High screen time was associated with poor sleep quality (OR = 1.45; 95 %CI = 1.01-2.12) and insufficient sleep duration (OR = 1.52; 95 %CI = 1.01-2.03) in adolescents insufficiently active. There were no associations between screen time and sleep parameters in active adolescents. Conclusion: High screen time was associated with poor sleep quality and insufficient sleep duration only in insufficiently active adolescents. These results suggest that high PA levels may contribute to improving sleep patterns in pediatric population.

The relevance of the optional use of fasting in laboratory measurements that make up the lipid profile: A systematic literature review.

The objective of this study was to evaluate the impact of fasting easing on laboratory measurements of the lipid profile, in order to contribute to the fidelity of interpretation of laboratory results. Starting in October 2022, a Systematic Literature Review (SRL) was carried out, using articles indexed in the electronic databases PubMed/MEDLINE, EMBASE, Scopus, LILACS and Cochrane Library, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Group (PRISMA). This RSL was registered with PROSPERO, under registration number CRD42022370007. For inclusion, articles had to be original and developed in humans. After evaluating the methodological quality and analyzing the risk of bias, we obtained 16 articles published between 1994 and 2021, providing data on a total of 398,709 individuals, aged between 3 and 93 years. According to the selected studies, lipid profile measurements performed with flexible fasting, in addition to bringing benefits to patients and the pre-analytical system of the clinical laboratory, are more suitable for determining cardiovascular risk, mainly through the assessment of values obtained in the determination of triglycerides. It is therefore concluded that the optional use of fasting must be established through medical advice. In addition, laboratory methods and readings must be readjusted to this reality, informing through the report the parameters related to the lipid profile with and without the use of a 12-hour fast.

Quality indicators in prolonged hemodialysis with regional citrate anticoagulation with the genius system: retrospective cohort of critical patients with acute kidney injury.

BACKGROUND: Prolonged hemodialysis (HD) is performed from 6 to 12 h and can last up to 24 h. To prevent system clotting some studies suggest that Regional Citrate Anticoagulation (RCA) use reduces bleeding rates relative to systemic heparin. However, there may be difficulties in the patient's clinical management and completing the prescribed HD with Genius system using RCA. OBJECTIVE: To analyze safety Quality Indicators (IQs) and follow up on prolonged HD with 4% sodium citrate solution in a Genius® hybrid system. METHODS: This is a retrospective cohort conducted in an intensive care unit. RESULTS: 53 random sessions of prolonged HD with 4% sodium citrate solution of critically ill patients with AKI assessed. Evaluated safety indicators were dysnatremia and metabolic alkalosis, observed in 15% and 9.4% of the sessions, respectively. Indicators of effectiveness were system clotting which occurred in 17.3%, and the minimum completion of the prescribed HD time, which was 75.5%. CONCLUSION: The assessment of the indicators showed that the use of RCA with a 4% sodium citrate solution in prolonged HD with the Genius system in critically ill patients with AKI can be performed in a simple, safe, and effective way.

Is natural better? An ecotoxicity study of anthraquinone dyes.

The concept of sustainability has gained prominence in recent years, enhancing the need to develop products that are less harmful to the environment. Dyes are used by various industrial sectors and have a lot of market value; they are used on a large scale mainly by the textile industry that uses large volumes of water and is one of the main contributors to the contamination of water bodies. Some natural compounds, especially anthraquinones are re-emerging as possible alternatives to synthetic dyes, some of which are known for their toxic and/or mutagenic effects. The BioColour project (https://biocolour.fi/) which is interested in promoting the development of new alternative molecules to synthetic dyes, provided us highly purified anthraquinone dyes dermocybin and dermorubin (>98% purity) extracted from a specie of fungus Cortinarius sanguineus. Dyes were tested for their acute and chronic toxicity using different aquatic organisms. Dermorubin was not toxic to any of the organisms tested for the highest test concentration of 1 mg L-1 and it was the most promising dye. Dermocybin was toxic to Daphnia similis (EC50 = 0.51 mg L-1), Ceriodaphnia dubia (IC10 = 0.13 mg L-1) and Danio rerio embryos (extrapolated LC50 = 2.44 mg L-1). A safety limit, i.e, predicted no-effect concentration (PNEC) of 0.0026 mg L-1 was derived based on the toxicity of dermocybin. The PNEC value can be used to provide hazard information for future application in commercial dyeing processes. Then, we compared the toxicity of dermocybin and dermorubin with ecotoxicity data available in the literature on other anthraquinone dyes of natural and synthetic origin. Some natural dyes can be as toxic as synthetic ones, or more toxic when chronic effects are considered. Despite natural dyes being used since centuries past, there are few ecotoxicological studies available. This study is designed to help develop a more comprehensive understanding of their toxicological properties.

Proposal of a chronic toxicity test using the tropical epibenthic amphipod Parhyale hawaiensis.

Chronic toxicity tests with representative organisms are essential for ecological risk assessment. The circumtropical marine amphipod Parhyale hawaiensis is a promising test organism in ecotoxicology. This study aimed to develop a chronic toxicity protocol for liquid samples testing with P. hawaiensis using reproduction and growth as endpoints. In the proposed protocol, organisms (≤52 days old) are placed in 5 replicates each containing 100 mL of solution, 10 organisms, and 5 g of crushed coral for 42 days of exposure. The protocol was successfully developed but reproduction showed better performance than growth rate. NOECs based on reproduction were determined for zinc (0.10 mg Zn L-1) and 3,4-DCA (0.50 mg L-1), and they are of the same order of magnitude compared with the values of other amphipods. The developed test based on reproduction can be considered a promising tool for hazard characterizations although more tests with different substances are still needed.

POMONA: a multiplatform software for modeling seed physiology.

Seed physiology is related to functional and metabolic traits of the seed-seedling transition. In this sense, modeling the kinetics, uniformity and capacity of a seed sample plays a central role in designing strategies for trade, food, and environmental security. Thus, POMONA is presented as an easy-to-use multiplatform software designed to bring several logistic and linearized models into a single package, allowing for convenient and fast assessment of seed germination and or longevity, even if the data has a non-Normal distribution. POMONA is implemented in JavaScript using the Quasar framework and can run in the Microsoft Windows operating system, GNU/Linux, and Android-powered mobile hardware or on a web server as a service. The capabilities of POMONA are showcased through a series of examples with diaspores of corn and soybean, evidencing its robustness, accuracy, and performance. POMONA can be the first step for the creation of an automatic multiplatform that will benefit laboratory users, including those focused on image analysis.

Solfeggio-frequency music exposure reverses cognitive and endocrine deficits evoked by a 24-h light exposure in adult zebrafish.

Music therapy has long been used as a non-pharmacological intervention to improve cognitive function and mood in humans. Mounting rodent evidence also supports beneficial impact of music exposure on animal cognitive performance. The zebrafish (Danio rerio) is an important emerging aquatic animal model in translational biomedical and neuroscience research. Here, we evaluate the effects of intermittent (2-h or 6-h twice daily) and continuous (24-h) solfeggio-frequency music exposure on behavioral, cognitive and endocrine parameters in adult zebrafish whose circadian rhythm was disturbed by a 24-h light exposure. Overall, a 24-h light exposure stress evokes overt cognitive deficits in the inhibitory avoidance test and elevates zebrafish whole-body cortisol levels. However, these effects were reversed by solfeggio-frequency music exposure for 2 or 6 h twice daily, and by continuous 24-h exposure. Collectively, these findings suggest a positive modulation of cognitive and endocrine responses in adult zebrafish by environmental enrichment via the long-term exposure to music, and reinforces zebrafish as a robust, sensitive model organism for neurocognitive and neuroendocrine research.

The Effect of Magneto-Priming on the Physiological Quality of Soybean Seeds.

Microwaves have been applied to the drying of seeds of several species due to their maintenance of the quality of the seeds and reduction of time and costs. However, few is known about the effect of microwaves on the increase of the physiological quality of soybean seeds and especially their effects on longevity. Therefore, the use of microwaves as magneto-priming in soybean seeds was the object of study in this work. For this purpose, two soybean cultivars were selected and submitted to the ultra-high frequency (UHF) microwave exposure of 2.45 GHz, in the wavelength of 11 cm, and power of 0.2 W/g, for 15 min. The results showed that this condition of exposure to the microwave brought benefits in both cultivars after treatment. Incremental improvements were observed in the germinability indexes, the seedling length, the water absorption by the seeds, the fresh mass, dry mass, and longevity. The genes related to seed germination and longevity showed superior expression (HSFA3, HSP21, HSP17.6b, EXP, ABI3) with magneto-priming treatment. The data found ensure the use of the technique as a viable option for pre-treatment as magneto-priming in soybean seeds in order to improve seed quality.

Antimicrobial Effect of the Amniotic Membrane Isolated and Associated with Photodynamic Therapy.

Microbial control through alternative therapies, such as the amniotic membrane (AM) and antimicrobial photodynamic therapy (aPDT), has been gaining prominence with the advancement of bacterial resistance to conventional treatments. This study aimed to evaluate the antimicrobial effect of AM isolated and associated with aPDT using the PHTALOX® as a photosensitizer (PS) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. The groups studied were: C+; L; AM; AM+L; AM+PHTX; and AM+aPDT. The irradiation parameters were 660 nm, 50 J.cm-2, and 30 mW.cm-2. Two independent microbiological experiments were carried out in triplicate, and the results were analyzed by CFU/mL counting and a metabolic activity test, both statistically analyzed (p < 0.05). The integrity of the AM was verified after the treatments by a scanning electron microscope (SEM). The groups AM, AM+PHTX, and, mainly, AM+aPDT showed a statistical difference when compared to C+ regarding the decrease in CFU/mL and metabolic activity. SEM analysis showed significant morphological alterations in the AM+PHTX and AM+aPDT groups. The treatments with AM isolated or associated with PHTALOX® were adequate. The association had potentiated the biofilm effect, and the morphological differences presented by AM after treatment did not hinder its antimicrobial effect, encouraging its use in biofilm formation locals.

Influence of operating regime on resource recovery in aerobic granulation systems under osmotic stress.

Aerobic granular sludge (AGS) systems have great potential for biopolymers recovery, especially when subjected to adverse conditions. This work aimed to study the production of alginate-like exopolymers (ALE) and tryptophan (TRY) under osmotic pressure in conventional and staggered feeding regimes. The results revealed that systems operated with conventional feed accelerated the granulation, although less resistant to saline pressures. The staggered feeding systems favored better denitrification conditions and long-term stability. Salt addition gradient increase influenced biopolymers' production. However, staggered feeding, despite decreasing the famine period, did not influence the production of resources and extracellular polymeric substances (EPS). Sludge retention time (SRT), which was not controlled, proved to be an important operational parameter with negative influences on biopolymers' production in values greater than 20 days. Thus, the principal component analysis confirmed that the production of ALE at low SRT is related to better-formed granules with good sedimentation characteristics and good AGS performances.

Accuracy of Thermographic Imaging in the Early Detection of Pressure Injury: A Systematic Review.

OBJECTIVE: To verify the accuracy of thermographic images in the early detection of pressure injury (PI) in adult patients. DATA SOURCES: Between March 2021 and May 2022, researchers searched 18 databases for relevant articles using nine keywords. In total, 755 studies were evaluated. STUDY SELECTION: Eight studies were included in the review. Studies were included if they evaluated individuals older than 18 years who were admitted to any healthcare setting; were published in English, Spanish, or Portuguese; examined the accuracy of thermal imaging in the early detection of PI, including suspected stage 1 PI or deep tissue injury; and they compared the region of interest to another area or control group, or to the Braden Scale or Norton Scale. Animal studies and reviews, studies with contact infrared thermography, and those including stages 2, 3, 4, and unstageable PIs were excluded. DATA EXTRACTION: Researchers examined sample characteristics and assessment measures related to image capture, including environmental, individual, and technical factors. DATA SYNTHESIS: Across the included studies, sample sizes ranged from 67 to 349 participants, and patients were followed up for periods ranging from a single assessment up to 14 days, or until the appearance of a PI, discharge, or death. Evaluation with the infrared thermography identified temperature differentials between regions of interest and/or in comparison with risk assessment scales. CONCLUSIONS: Evidence on the accuracy of thermographic imaging in the early detection of PI is limited.

Impact of neuroinflammation on epigenetic transcriptional control of Sonic Hedgehog members in the central nervous system.

Sonic Hedgehog (Shh) signaling plays a critical role during central nervous system (CNS) development, and its dysregulation leads to neurological disorders. Nevertheless, little is known about Shh signaling regulation in the adult brain. Here, we investigated the contribution of DNA methylation on the transcriptional control of Shh signaling pathway members and its basal distribution impact on the brain, as well as its modulation by inflammation. The methylation status of the promoter regions of these members and the transcriptional profile of DNA-modifying enzymes (DNA Methyltransferases - DNMTs and Tet Methylcytosine Dioxygenase - TETs) were investigated in a murine model of neuroinflammation by qPCR. We showed that, in the adult brain, methylation in the CpG promoter regions of the Shh signaling pathway members was critical to determine the endogenous differential transcriptional pattern observed between distinct brain regions. We also found that neuroinflammation differentially modulates gene expression of DNA-modifying enzymes. This study reveals the basal transcriptional profile of DNMTs and TETs enzymes in the CNS and demonstrates the effect of neuroinflammation on the transcriptional control of members of the Shh Signaling pathway in the adult brain.

Influence of salt addition to stimulating biopolymers production in aerobic granular sludge systems.

The influence of salt addition to stimulating biopolymers production in aerobic granular sludge (AGS) systems was evaluated. The control systems (R1: acetate and R2: propionate) initially obtained less accumulation of mixed liquor volatile suspended solids (MLVSS), indicating that the osmotic pressure in the salt-supplemented systems (R3: acetate and R4: propionate) contributed to biomass growth. However, the salt-supplemented systems collapsed between days 110 and 130 of operation. R3 and R4 showed better performance regarding nutrients removal due to the greater abundance of nitrifying and denitrifying bacteria and phosphate-accumulating organisms. Salt also contributed to the higher production of biopolymers such as alginate-like exopolymers (ALE) per gram of volatile suspended solids (VSS) (R1: 397 mgALE∙gVSS-1, R2: 140 mgALE∙gVSS-1, R3: 483 mgALE∙gVSS-1, R4: 311 mgALE∙gVSS-1). Amino acids like tyrosine and tryptophan were better identified in extracellular polymeric substances extract from salt-operated reactors. This study brings important results in the context of resource recovery by treating saline effluents.

Stage-of-change Assessment Predicts Short-term Treatment Engagement for Opioid Use Disorder Patients Initiated on Buprenorphine.

INTRODUCTION: The emergency department (ED) is an effective setting for initiating medication for opioid use disorder (MOUD); however, predicting who will remain in treatment remains a central challenge. We hypothesize that baseline stage-of-change (SOC) assessment is associated with short-term treatment retention outcomes. METHODS: This is a longitudinal cohort study of all patients enrolled in an ED MOUD program over 12 months. Eligible and willing patients were treated with buprenorphine at baseline and had addiction medicine specialist follow-up arranged. Treatment retention at 30 and 90 days was determined by review of the Prescription Drug Monitoring Program. We used uni- and multivariate logistic regression to evaluate associations between patient variables and treatment retention at 30 and 90 days. RESULTS: From June 2018-May 2019, 279 patients were enrolled in the ED MOUD program. Of those patients 151 (54.1%) and 120 (43.0%) remained engaged in MOUD treatment at 30 and 90 days, respectively. The odds of treatment adherence at 30 days were significantly higher for those with advanced SOC (preparation/action/maintenance) compared to those presenting with limited SOC (pre-contemplation/contemplation) (60.0% vs 40.8%; odds ratio 2.18; 95% confidence interval 1.15 to 4.1; P <0.05). At 30 days, multivariate logistic regression determined that advanced SOC, age >40, having medical insurance, and being employed were significant predictors of continued treatment adherence. At 90 days, advanced SOC, non-White race, age > 40, and having insurance were all significantly associated with higher likelihood of treatment engagement. CONCLUSION: Greater stage-of-change was significantly associated with MOUD treatment retention at 30 and 90 days post index ED visit.

Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis.

Paracoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB/c mice infected with P. brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, α-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-ß1 and fibronectin and high levels of MMP-2 and IFN-γ were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response.

PLGA-PVA-PEG Single Emulsion Method as a Candidate for Aminolevulinic Acid (5-ALA) Encapsulation: Laboratory Scaling Up and Stability Evaluation.

One of the most widely used molecules used for photodynamic therapy (PDT) is 5-aminolevulinic acid (5-ALA), a precursor in the synthesis of tetrapyrroles such as chlorophyll and heme. The 5-ALA skin permeation is considerably reduced due to its hydrophilic characteristics, decreasing its local bioavailability and therapeutic effect. For this reason, five different systems containing polymeric particles of poly [D, L-lactic-co-glycolic acid (PLGA)] were developed to encapsulate 5-ALA based on single and double emulsions methodology. All systems were standardized (according to the volume of reagents and mass of pharmaceutical ingredients) and compared in terms of laboratory scaling up, particle formation and stability over time. UV-VIS spectroscopy revealed that particle absorption/adsorption of 5-ALA was dependent on the method of synthesis. Different size distribution was observed by DLS and NTA techniques, revealing that 5-ALA increased the particle size. The contact angle evaluation showed that the system hydrophobicity was dependent on the surfactant and the 5-ALA contribution. The FTIR results indicated that the type of emulsion influenced the particle formation, as well as allowing PEG functionalization and interaction with 5-ALA. According to the 1H-NMR results, the 5-ALA reduced the T1 values of polyvinyl alcohol (PVA) and PLGA in the double emulsion systems due to the decrease in molecular packing in the hydrophobic region. The results indicated that the system formed by single emulsion containing the combination PVA-PEG presented greater stability with less influence from 5-ALA. This system is a promising candidate to successfully encapsulate 5-ALA and achieve good performance and specificity for in vitro skin cancer treatment.