A new acridone with antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans.

AIM: The increase in the number of fungal infections worldwide, coupled with the limitations of current antifungal chemotherapy, demand the development of safe and effective new antifungals. Here, we presented the synthesis of a novel acridone (M14) and its antifungal properties against Candida and dermatophytes species. METHODS AND RESULTS: A series of 17 acridones was designed, synthesized and tested for its antifungal activity. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Only the acridone M14 showed growth-inhibitory activity against reference strains and clinical isolates of Candida and dermatophytes, with MIC range of 7·81-31·25 µg ml-1 . Moreover, M14 exhibited fungicidal activity and prevented biofilm formation by C. albicans as well as reduced the viability of preformed biofilms, even at sub-MICs. The confocal laser scanning microscopy analysis revealed that C. albicans hyphal growth was completely inhibited in the presence of M14. Similarly, there was a severe inhibition on hyphal growth of Trichophyton rubrum. We also found that M14 has relatively low toxicity to human fibroblasts. CONCLUSIONS: The new acridone M14 has antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans. In addition, M14 is relatively selective to fungal cells compared to human normal cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its in vitro antifungal activity, anti-Candida biofilm effect and moderate cytotoxicity towards normal human cell, M14 may serve as a valuable lead compound to develop a new antifungal agent.

Identification and antifungal susceptibility of fungi isolated from dermatomycoses.

BACKGROUND: Dermatomycoses are superficial fungal infections of the skin, hair and nails that affect more than 20-25% of the people worldwide. These infections can be caused by yeasts, dermatophytes and non-dermatophyte filamentous fungi (NDFF) and are considered a public health problem. Despite this, few studies have investigated the prevalence and antifungal susceptibility of causative agents of dermatomycoses in the developing world. OBJECTIVES: The aims of this study were to identify and determine the antifungal susceptibility profile of yeast and filamentous fungi isolated from dermatomycoses in Uberaba, Minas Gerais, Brazil. METHODS: Specimens were obtained from patients with clinically diagnosed and laboratory confirmed dermatomycosis between July 2009 and July 2011. Fungal identification was based on classical methods and antifungal susceptibility testing was performed by broth microdilution method. RESULTS: Of the 216 fungal isolates, 116 (53.8%) were yeasts, 70 (32.4%) dermatophytes and 30 (13.8%) NDFF. Onychomycosis was the most common clinical condition. Candida parapsilosis (24.1%) and Trichophyton rubrum (17.1%) were the fungi most frequently isolated. Voriconazole, ketoconazole and itraconazole were the most potent antifungal agents against yeast, whereas terbinafine, voriconazole and itraconazole had a high in vitro activity against dermatophytes. Overall, the antifungal agents had little or no activity against NDFF and the highest minimum inhibitory concentrations were those against Fusarium spp. CONCLUSION: Yeasts, particularly C. parapsilosis, play an important role as causative agents of dermatomycosis in our region. Our results suggest that the antifungal susceptibility testing coupled with proper identification of the fungi may be useful to assist clinicians in determining the appropriate therapy for dermatomycoses.

Periodontal outcomes of children and adolescents with attention deficit hyperactivity disorder: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to answer the following question: Are children and adolescents with attention deficit hyperactivity disorder (ADHD) more likely to have gingival or periodontal disease-related outcomes than their non-ADHD peers? METHODS: Searches were conducted in the following databases: Embase, Scopus, Web of Science, and PubMed. Google Scholar and OpenGrey were also verified. Observational studies were included in which children and adolescents with ADHD were compared with their healthy peers in terms of gingival and/or periodontal endpoints. Bias appraisal was performed using the Joann Briggs tool for case-control and cross-sectional studies. Meta-analysis was performed using R language. Results are reported as mean difference (MD) and odds ratio (OR). Statistical analyses were performed in RStudio. RESULTS: A total of 149 records were identified in the searches. Seven studies were included. The meta-analysis showed that children and adolescents with ADHD had a higher mean gingival bleeding index (percentage) than their non-ADHD peers (MD = 11.25; CI = 0.08-22.41; I2 = 73%). There was no difference between groups for plaque index (MD = 4.87; CI = - 2.56 to 12.30; I2 = 63%) and gingivitis (OR = 1.42; CI = 0.22-9.21; I2 = 76%). Regarding the assessment of risk of bias, the major issue found in the articles was the absence of analyses for the control of confounding factors. CONCLUSION: Children and adolescents with ADHD had more gingival bleeding than their non-ADHD peers, but no difference regarding plaque or gingivitis was detected between groups. CLINICAL REGISTRATION: CRD42021258404.

Evaluation of white water reuse in the bleaching process for reducing fresh water consumption.

The main objective of this work is to study the technical viability of using the effluent generated in paper machines (white water) in the wash presses of the bleaching stage, reducing fresh water consumption. As a case study, the industrial process of Ripasa S.A. Celulose e Papel was evaluated. White water rate is about 700 m3/h and it is not possible to reuse all this volume in the bleaching stage without causing operational problems (fouling in tubes and clogging in the screens). A mass balance of the bleaching unit was developed in an electronic spreadsheet in order to evaluate the possibility of reducing fresh water consumption, using only a fraction of the available white water in the wash presses. To achieve this objective some physical-chemistry properties of the white water stream and of other streams of the process were determined. The maximum concentration of some non-process elements (Si, Ca, Mn and Fe), which could accumulate in the process, were determined in order to establish some parameters to allow process integration of the streams involved, considering operational constraints. The results obtained have shown that it is possible to reduce approximately by 13% the consumption of fresh water and this methodology has been satisfactory.

Vasoactive intestinal peptide stimulates prostate-specific antigen secretion by LNCaP prostate cancer cells.

The secretion of prostate-specific antigen (PSA) by prostate cancer provides an important tool in the diagnosis and management of this disorder. While androgens are required for PSA synthesis, the neuroendocrine regulation of PSA secretion is less understood. Human prostate is extensively innervated with vasoactive intestinal peptide (VIP)-containing neurons, while both normal and malignant prostate cells contain VIP receptors. Therefore, we investigated the effects of VIP on PSA secretion by LNCaP prostate cancer cells. We found that 1-4-h VIP treatment produces 60-100% increases in PSA secretion by LNCaP cells. Increases in PSA secretion were seen with as little as 10(-10) M VIP with maximum effects at 10(-7) M. The predominant acute effect of VIP was to increase the secretion of stored PSA without increasing PSA mRNA. VIP's effect on PSA secretion involved the production of intracellular cAMP since all doses of VIP which increased secretion were associated with increased cyclic AMP and since dibutyryl-cyclic AMP treatment increased secretion similarly to VIP. These results suggest that VIP regulates PSA secretion by prostate cancer cells and also suggest a role for VIP to regulate PSA secretion by normal prostate epithelial cells.

Very low optical absorptions and analyte concentrations in water measured by Optimized Thermal Lens Spectrometry.

Thermal Lens Spectrometry has traditionally been carried out in the single-beam and the mode-mismatched dual-beam configurations. Recently, a much more sensitive dual-beam TL setup was developed, where the probe beam is expanded and collimated. This feature optimizes Thermal Lens (TL) signal and allows the use of thicker samples, further improving the sensitivity. In this paper, we have made comparisons between the conventional and optimized TL configurations, and presented applications such as measurements of very low absorptions and concentrations in water and Cr(III) aqueous solution in the UV-vis range. For pure water we found linear absorption coefficients as low as the Raman scattering one due to the stretching vibrational modes of OH group. The detection limit was estimated 1 × 10(-6)cm(-1) with a 180-mW excitation power using a 100-mm cell length. This sensitivity is very high, considering that water has a photothermal enhancement factor ∼ 33 times smaller than CCl(4), for example. For Cr(III) species in aqueous solution, the limit of detection (LOD) was estimated in ∼ 40 ng mL(-1) at 514 nm, or ∼ 10 ng mL(-1) at 405 nm, which is ∼ 30 times smaller than the LOD achieved with conventional transmission techniques. The more recent TL configuration is very attractive to obtain absorption spectra, since the result does not depend critically on the beam parameters, unlike the other configurations. The main drawbacks of this optimized TL configuration are the longer acquisition time and the need for larger samples.

Study on the observation of Eu2+ and Eu3+ valence states in low silica calcium aluminosilicate glasses.

The optical, magnetic and structural properties of Eu doped low silica calcium aluminosilicate glasses were investigated. The optical absorption coefficient presented two bands at 39,246 and 29,416 cm(-1), which were assigned respectively to the [Formula in text], and [Formula in text] transitions of Eu(2+). The fluorescence measured at 300 K on a sample doped with 0.5 wt% of Eu(2)O(3) exhibited a broad band centered at 17,350 cm(-1), which is attributed to the [Formula in text] transition of Eu(2+), whereas the additional peaks are due to the [Formula in text] transitions of Eu(3+). From magnetization and XANES data it was possible to evaluate the fractions of Eu(2+) and Eu(3+) for the sample doped with 0.5 and 5.0 wt% of Eu(2)O(3), the values of which were approximately 30 and 70%, respectively.

Microwave drying effects on dichromated gelatin holograms.

Exposing dichromated gelatin holograms to microwave radiation considerably increases their resistance to heating, either for wide or narrowband holograms. No wavelength shift was observed for the former and only a small shift was observed for the latter. This behavior can be explained in the framework of Chang's models, taking into account the effects of microwaves on polar molecules and the potential positions of the water molecules within the medium. These results and their interpretation suggest further experiments to measure the different environments of the water molecules inside the gelatin and to use microwaves at the resonance frequencies of the water.

A mitogenic signal triggered at an early stage of vaccinia virus infection: implication of MEK/ERK and protein kinase A in virus multiplication.

Vaccinia virus (VV) triggers a mitogenic signal at an early stage of infection. VV-induced proto-oncogene c-fos mRNA with kinetics paralleling that stimulated by serum. The VV virokine, or vaccinia virus growth factor (VGF), was not crucial for c-fos induction because it was observed upon infection with the virokine-minus mutant VV (VGF(-)). Furthermore, c-fos expression did not require infectious virus particles, as it occurred even with UV-inactivated VV and was equally induced by the different multiplicities of infection, i.e. 1.0, 5.0, and 25.0. c-fos expression was preceded by VV-induced DNA binding activity and was mediated via the cis-acting elements serum response element (SRE), activating protein-1 (AP-1), and cAMP-response element (CRE). VV activated the protein kinases p42MAPK/ERK2 and p44MAPK/ERK1 and the transcription factor ATF1 in a time-dependent manner with kinetics that paralleled those of VV-stimulated DNA-protein complex formation. The mitogenic signal transmission pathways leading to c-fos activation upon VV infection were apparently mediated by the protein kinases MEK, ERK, and PKA. This assumption was based on the findings that: 1) c-fos transcript was down-regulated; 2) the SRE, AP-1, and CRE binding activities were significantly reduced; and 3) the activation of p42MAPK/ERK2, p44MAPK/ERK1, and ATF1 were drastically affected when the viral infections were carried out in the presence of specific protein kinase inhibitor. Moreover, the mutant VV (VGF(-)) was also able to activate ERK1/2. It is noteworthy that virus multiplication was equally affected by the same kinase inhibitors. Taken together, our data provide evidence that the early mitogenic signal triggered upon VV infection relies upon the activation of the protein kinases MEK, ERK, and PKA, which are needed for both signal transduction and virus multiplication.