Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis.

PURPOSE: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development. METHODOLOGY: We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0). RESULTS: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg. CONCLUSIONS: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development.

Safety and tolerability of cinnamaldehyde in orabase for oral candidiasis treatment: phase I clinical trial.

OBJECTIVE: To advance studies on the effect of a new pharmaceutical formulation for the treatment of oral fungal infections, we evaluated the safety and tolerability of orabase ointment containing cinnamaldehyde for use on the oral mucosa. MATERIAL AND METHODS: A clinical trial (phase I) was carried out on 35 individuals with healthy oral mucosa divided into three groups: ointments at 200 µg/mL, n = 12; 300 µg/mL, n = 11; and 400 µg/mL, n = 12. Product safety was assessed using three parameters: (a) clinical evolution as recorded by trained examiners; (b) evolution of the inflammatory process as registered by an exfoliative cytology exam and analyzed by trained pathologists; (c) mucosal swab to count Candida spp. colony-forming units (CFU). These parameters were analyzed both beforehand and at 15 days of treatment. RESULTS: The three ointment concentrations evaluated did not trigger inflammatory processes. The mycological analyses revealed a reduction of at least 99% in the number of Candida spp. CFU. In the exfoliative cytology analyses, the cells were found to be healthy. Participants reported a pleasant taste, yet 17% reported a slight burning sensation when applying the product. CONCLUSIONS: The ointment is safe and tolerable for use on healthy oral mucosa. TRIAL REGISTRATION: Registration number: RBR-7zwzs3. CLINICAL RELEVANCE: The ointment proved to be safe and tolerable for use on oral mucosa, encouraging studies to evaluate its clinical efficacy in patients with oral candidiasis, and contributing to a new therapeutic proposal for the treatment of fungal infections caused by Candida spp.

Effects of long-term cinnamaldehyde immersion on the surface roughness and color of heat-polymerized denture base resin.

STATEMENT OF PROBLEM: Cinnamaldehyde has been successfully used for the short-term disinfection of dentures; however, its long-term effects on the surface and color properties of denture base materials remain unknown. PURPOSE: The purpose of this in vitro study was to evaluate the effects of simulated immersion in cinnamaldehyde for up to 5 years on the surface roughness and color parameters of a heat-polymerized denture resin. MATERIAL AND METHODS: Eighty Ø10×5-mm disk-shaped specimens were prepared from microwave heat-polymerized polymethylmethacrylate (PMMA) and immersed in 4 solutions (n=20): TW-tap water (control), SH - 0.5% sodium hypochlorite, PX-alkaline peroxide, and CA-cinnamaldehyde (27 µg/mL). The immersion protocol simulated 104 cycles (3.5 months), 913 cycles (2.5 years), and 1825 immersion cycles (5 years) of a daily immersion cleaning protocol, with immersion times ranging from 10 to 20-minutes. Surface roughness (Sa) and the color parameters of CIELab (L∗ a∗ b∗, ΔEab), CIEDE2000 (ΔE00), and the National Bureau of Standards (NBS) were analyzed at baseline (t=0) and after the immersion cycles. The data were analyzed by 2-way analysis of variance (ANOVA) for repeated measures and the Tukey post hoc test (α=.01). RESULTS: Sa was significantly increased in all groups after 1825 cycles compared with baseline (P<.01), regardless of the solution. Only the time factor significantly affected ΔEab, ΔE00, and NBS parameters, which were below the perceptibility and acceptability thresholds. After a simulated 5-year immersion, the surface roughness and color values of CA-treated specimens were not statistically different from those of the other groups (P>.01). CONCLUSIONS: Cinnamaldehyde solution (27 µg/mL) produced minor effects on the surface roughness and color parameters of a heat-polymerized denture base resin similar to those of 0.5% sodium hypochlorite and alkaline peroxide after a 5-year simulated immersion.

Integrated oral care contributes positively to the course of treatment of oncopediatric patients.

The purpose of this study was to implement a model of permanent oral health care for oncopediatric patients and to observe its effects on severe oral mucositis and subsequent treatment interruptions. We performed a quasi-experimental study in the Pediatric Department of Napoleão Laureano Hospital, in the city of João Pessoa, Brazil. A integrated oral care was implemented by a dentistry team for prevention of comorbidities, such as infections, oral pain, oral function maintenance, oral mucositis, and interventions for lesions due to severe oral mucositis. The oral comorbidities were compared before and after the implementation. The duration of severe oral mucositis (SOM) before and after the interventions and the interruptions in treatment due to SOM were the main outcome measures. Permanent oral health care reduced the duration of SOM and reduced pediatric chemotherapy interruptions due to SOM by 81.8%.Conclusion: The permanent oral health care to offer to oncopediatric patients increased surveillance regarding oral comorbidities and reduced chemotherapy interruptions due to severe oral mucositis. This care plan could be adopted anywhere around the world. What is Known: • Several studies on oral care for pediatric oncology patients, especially regarding both prevention of and treatment for oral mucositis during antineoplastic therapy, have been published. What is New: • This study describes the benefits of permanent oral care with daily oral surveillance for pediatric patients, which reduced the duration of severe oral mucositis, increased surveillance and the efficiency in diagnostic for signs of oral mucositis, enabling early intervention, and decreased chemotherapy interruptions, contributing positively to the course of treatment.

Antifungal activity of Punicalagin-nystatin combinations against Candida albicans.

OBJECTIVES: Oral candidiasis is the most common opportunistic fungal infection of oral mucosa and results from an overgrowth of Candida, especially Candida albicans. The potential anti-C. albicans and cytotoxicity of punicalagin (PCG), isolated from Punica granatum, alone or with nystatin (NYS) were evaluated. METHODS: Activity of compounds alone or in combinations was determined against two C. albicans strains (ATCC 90028 and SC5314). Minimal inhibitory concentration (MIC)-50 and Minimum Fungicidal Concentration (MFC) were assessed by XTT assay and CFU counts, respectively. For combinations, determination of fractional inhibitory concentration index was performed. Ergosterol pathway was investigated as a possible PCG antifungal mechanism. Cytotoxicity assays were undertaken on human primary oral keratinocytes and gingival fibroblasts incubated with antifungal concentrations of PCG and/or NYS for 24 hr. RESULTS: Combination of NYS and PCG increased antifungal efficacy, compared with compounds tested alone. Combinations 4 (PCG-6.25 µg/ml; NYS-3.9 µg/ml) and 5 (PCG-12.5 µg/ml; NYS-1.95 µg/ml) were more effective since they reduced the MIC-50 of PCG (50 µg/ml) by 8 and 4 times, respectively, increased the candidal inhibition and nullified the PCG cytotoxicity for keratinocytes. PCG antifungal mechanism did not involve ergosterol biosynthesis pathway. CONCLUSIONS: The favorable outcomes for combination of PCG and NYS encourage further testing this therapeutic strategy against C. albicans.

Cinnamaldehyde is a biologically active compound for the disinfection of removable denture: blinded randomized crossover clinical study.

BACKGROUND: Fungal infections associated with the use of dentures, like denture stomatitis, are difficult to prevent and treat. This in situ study aimed to investigate the efficacy of cinnamaldehyde for the disinfection of complete removable dentures, and the effect on the physical and mechanical properties (Vickers microhardness, color, and surface roughness) of the acrylic resin. METHODS: Acrylic resin disks were inserted into the dentures of a probabilistic sample of 33 complete denture users, that used cinnamaldehyde (27 µg/mL) and 0.5% sodium hypochlorite solutions in a 20 min/7-days protocol of dentures immersion in each solution, with a wash-out period of 7 days, to constitute a crossover-study. The disks were analyzed before and after the immersion, for the presence of microorganisms (CFU/mL) and by scanning electron microscope (SEM). Also, the surface roughness (Ra) and Vickers microhardness were measured, and color parameters were analyzed using the National Bureau of Standards (NBS) method. Data was analyzed by Wilcoxon and Friedman (microbiological evaluation), paired t-test (color and roughness) and independent t-test (Vickers hardness) (α = 0.05). RESULTS: A significant reduction (P < 0.05) in the number of microorganisms was observed for each species (total microorganisms, Streptococcus mutans, and Candida spp.), with no significant differences (P > 0.05) between hypochlorite and cinnamaldehyde. There was an increase in the roughness and a decrease in the hardness of the test specimens, with no difference between the two disinfectant substances (P > 0.05). Both hypochlorite and cinnamaldehyde also caused changes in color, considered as "perceptible" by the NBS classification, but with no significant difference between disinfectant substances (P < 0.05), and under the clinically acceptable limit (ΔE ≤ 3.7). CONCLUSION: The 27 µg/mL cinnamaldehyde solution was effective against all evaluated microorganisms and caused minor alterations in hardness, surface roughness, and color parameters, with no clinical relevance.

Alternative Animal and Non-Animal Models for Drug Discovery and Development: Bonus or Burden?

Mammalian models have served as a basis for R&D over the past decades. Nevertheless, these models are expensive, laborious, may yield results that cannot always be translated into the human in vivo situation and, more recently, have reverberated great social and ethical dilemmas. Hence, the prospect of changes in the global scientific scenario and the Three Rs principle (Reduction, Replacement and Refinement) have encouraged the development of alternative methods to the use of mammals. Despite the efforts, suitable alternative tests are not available in all areas of biomedical research, as regulatory acceptance requires time, prior validation and robust financial and scientific investment. In this perspective, we aim to shed light on the concepts, challenges and perspectives for implementation of innovative alternative animal and non-animal methods in scientific research. The applicability and meaningfulness of invertebrate animal models, in silico analysis and reverse pharmacology are discussed, among other aspects of relevance in today's scenario. Overall, the use of alternative models, including Artemia salina (brine shrimp), Caenorhabditis elegans (roundworm), Danio rerio (zebra fish), Drosophila melanogaster (fruit fly), Galleria mellonella (greater waxmoth) and in silico modelling, increased 909% from 1990 to 2015, as compared to 154% of conventional mammals in the same period. Thus, technological and scientific advancements in the fields of toxicology and drug development seem to have diminished the need for mammalian models. Today, however, mammals still remain critically indispensable to provide - in most cases -reliable data subsidizing and validating translation into the clinical setting.

Microbial contamination in intraoral phosphor storage plates: the dilemma.

OBJECTIVES: The aims of this study were to evaluate microbial contamination in phosphor storage plates in dental radiology services and discuss the possible origin of this contamination. MATERIALS AND METHODS: The sample comprised 50 phosphor plates: 14 plates from service A, 30 from service B, and 6 in the control group, consisting of plates never used. Damp sterile swabs were rubbed on the phosphor plates, and then transferred to tests tubes containing sterile saline solution. Serial dilutions were made, and then inoculated in triplicate on Mueller Hinton agar plates and incubated at 37 °C/48 h, before counting the colony-forming units (CFU). The samples were also seeded in brain-heart infusion medium to confirm contamination by turbidity of the culture medium. All solutions, turbid and clean, were seeded in selective and non-selective media. RESULTS: At service A and B, 50 and 73.3 % of the phosphor plates were contaminated, respectively. This contamination was mainly due to bacteria of the genus Staphylococcus. CFU counts ranged from 26.4 to 80.0 CFU/plate. CONCLUSIONS: Most of the phosphor plates evaluated shown to be contaminated, mainly by Staphylococcus ssp. Quantitatively, this contamination occurred at low levels, possibly arising from handling of the plates. The use of a second plastic barrier may have diminished contamination by microorganisms from the oral cavity. CLINICAL RELEVANCE: There is a risk of cross-contamination by phosphor storage plates used in dental radiology services.

Relationship between Risk Behavior for Eating Disorders and Dental Caries and Dental Erosion.

The aim of this study was to evaluate whether there is an association between risk behavior for eating disorders (EDs) and dental erosion and caries. A controlled cross-sectional study was conducted in Brazil, involving 850 randomly selected female adolescents. After evaluating risk behavior for eating disorders through the Bulimic Investigatory Test of Edinburgh, 12 adolescents were identified with severe risk behavior for EDs and matched to 48 adolescents without such risk. Dental examinations, anthropometric measurements, and eating habits and oral hygiene were performed. Adolescents with high severity eating disorder condition were not more likely to show dental caries (p = 0.329; OR = 2.2, 95% CI: 0.35-13.72) or dental erosion (p = 0.590; OR = 2.33; 95% CI: 0.56-9.70). Adolescents with high body mass index (BMI) were five times more likely to have high severity eating disorder condition (p = 0.031; OR = 5.1; 95% CI: 1.61-23.07). Therefore, high severity risk behavior for EDs was not significantly associated with dental caries and dental erosion. However, high BMI was a risk factor for developing eating disorders and should be an alert for individuals with this condition.

Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: an in vitro study.

BACKGROUND: Limitations of antifungal agents used in the treatment of oral candidiasis, as the development of resistant strains, are known by the scientific community. In this context, the aim of this study was to evaluate the antifungal activity of thymol against Candida albicans, Candida tropicalis and Candida krusei strains and to determine its mode of action and synergistic effect when combined with the synthetic antifungal nystatin. METHODS: The minimum inhibitory concentration (MIC) was determined using a microdilution technique, and the minimum fungicidal concentration (MFC) was determined via subculture sowing. The mode of action of thymol was established by verifying fungal growth in the presence of sorbitol or ergosterol. The fractional inhibitory concentration index (FIC) was determined using the checkerboard method. RESULTS: Thymol presented an antifungal effect, with MICs of 39 µg/mL for C. albicans and C. krusei and 78 µg/mL for C. tropicalis. The results of the antifungal test remained unchanged in the presence of sorbitol; however, the MIC value of thymol against C. albicans increased eight times (from 39.0 to 312.5 µg/mL) in presence of exogenous ergosterol. The combination of thymol and nystatin reduced the MIC values of both products by 87.4%, generating an FIC index of 0.25. CONCLUSIONS: Thymol was found to have a fungicidal effect on Candida species and a synergistic effect when combined with nystatin.

Inhibition of adherence of C. albicans to dental implants and cover screws by Cymbopogon nardus essential oil and citronellal.

OBJECTIVE: This study investigated the biological activity of the essential oil from Cymbopogon nardus and of the phytoconstituent citronellal on Candida strains as to the inhibition of adherence to dental implants and cover screws. MATERIAL AND METHODS: The essential oil was analyzed by gas chromatography coupled to mass spectrometry (GC-MS) and had its MIC and MFC determined against 12 strains of Candida. Then, tests of inhibition of adherence to the dental implants and cover screws were carried out using the MIC of the substances, followed by scanning electron microscopy analysis. Nystatin and chlorhexidine were used as positive controls, and experiments were performed in triplicate. RESULTS: The analysis by GC-MS of the essential oil identified citronellal as the major compound. The MICs of the essential oil, citronellal, chlorhexidine, and nystatin--able to inhibit 100 % of the strains--were found to be 64, 512, 64, and 32 µg/ml, respectively. The essential oil significantly inhibited the adherence of Candida albicans to the dental implants and cover screws (p < 0.001). Citronellal inhibited yeast adherence only to the dental implants (p < 0.001), and no significant results were found for the cover screws (p > 0.05) compared to the growth control. CONCLUSION: The essential oil and citronellal have proven antifungal activity and are able to inhibit the in vitro adherence of C. albicans. CLINICAL RELEVANCE: There has been a search for alternative natural product-containing formulations that should be effective in inhibiting adherence of yeasts to the surfaces of materials and also able to treat oral fungal infections. Further trials could make these products an alternative to chemical removal of peri-implant biofilm.

Use of alcohol vinegar in the inhibition of Candida spp. and its effect on the physical properties of acrylic resins.

BACKGROUND: Given the high prevalence of oral candidiasis and the restricted number of antifungal agents available to control infection, this study investigated the in vitro antifungal activity of alcohol vinegar on Candida spp. and its effect on the physical properties of acrylic resins. METHODS: Tests to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of vinegar alcohol (0.04 g/ml of acetic acid) and nystatin (control) were performed. The antifungal activity of alcohol vinegar was assessed through microbial growth kinetic assays and inhibition of Candida albicans adhesion to acrylic resin at different intervals of time. Surface roughness and color of the acrylic resin were analyzed using a roughness meter and color analyzer device. RESULTS: Alcohol vinegar showed MIC75% and MFC62.5% of 2.5 mg/ml, with fungicidal effect from 120 min, differing from nystatin (p < 0.0001), which showed fungistatic effect. Alcohol vinegar caused greater inhibition of C. albicans adhesion to the acrylic resin (p ≤ 0.001) compared to nystatin and did not change the roughness and color parameters of the material. CONCLUSION: Alcohol vinegar showed antifungal properties against Candida strains and caused no physical changes to the acrylic resin.

Antifungal Activity of Apple Cider Vinegar on Candida Species Involved in Denture Stomatitis.

PURPOSE: To evaluate the in vitro antifungal activity of apple cider vinegar on Candida spp. involved in denture stomatitis. MATERIAL AND METHODS: The microdilution technique was used to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of apple cider vinegar containing 4% maleic acid, and nystatin (control). Further tests of microbial kinetics and inhibition of adherence to acrylic resin were performed testing different concentrations (MIC, MICx2, MICx4) of the products at time intervals of 0, 30, 60, 120 and 180 minutes. A roughness meter was used to measure the changes in surface roughness; color change of the acrylic resin specimens exposed to the test products in different concentrations and time intervals were also evaluated. RESULTS: Apple cider vinegar (4%) showed MIC of 2500 µg/ml and MFC of 2500, 5000, and 10,000 µg/ml depending on the strain tested. Nystatin showed MIC of 3.125 µg/ml and strain-dependent MFC values ranging from 3.125 to 12.5 µg/ml. The microbial kinetic assay showed a statistical difference between apple cider vinegar and nystatin (p < 0.0001). After 30 minutes of exposure, apple cider vinegar showed fungicidal effect at MICx4, whereas nystatin maintained its fungistatic effect. Apple cider vinegar showed greater inhibition of adherence (p < 0.001) compared to control. Apple cider vinegar did not significantly alter the surface roughness of the acrylic resin specimens compared to nystatin (p > 0.05), and both had no influence on their color. CONCLUSION: Apple cider vinegar showed antifungal properties against Candida spp., thus representing a possible therapeutic alternative for patients with denture stomatitis.

Locked mouths: Tooth loss in a women's prison in northeastern Brazil.

BACKGROUND: Prisoners, in general, exhibit unsatisfactory oral conditions, especially with regard to the large number of missing teeth and with untreated caries. The aim of this study was to assess tooth loss, use of and need for prosthetic rehabilitation, and use of dental services among inmates. A cross-sectional study involving 65 inmates was developed at the Regional Women's Prison of Campina Grande, Brazil. Data regarding sociodemographic and sentencing profile, use of dental services, dental morbidity, and self-perceived oral health impacts were investigated. Chi-square, Pearson, and Kruskal-Wallis (P < 0.05) statistical tests were used. The mean tooth loss was 11.3 teeth. Significant association between tooth loss and oral health satisfaction (P = 0.049), self-perceived need for dental prosthesis (P < 0.001), uncomfortable teeth brushing (P = 0.005), difficult speaking (P = 0.002), and difficulty in performing routine tasks (P = 0.025) was observed. It was observed that 29.2% of inmates were using some type of prosthesis, all deemed unsuitable for use, and 78.5% of inmates needed prosthetic rehabilitation. The oral health condition of the population studied was found to be poor, and prisoners showed significant tooth loss and need for dentures, with the aggravation of having tooth extraction as the major reason for seeking dental care.

Antifungal activity against Candida albicans of methyl 3,5-dinitrobenzoate loaded nanoemulsion.

The objective of this study was to evaluate the antifungal activity of free methyl 3,5 dinitrobenzoate (MDNB) and its nanoemulsion (MDNB-NE) against strains of Candida albicans. Additionally, a molecular modeling study was also carried out to propose the mechanism of action and toxicity of MDNB. These results demonstrated the MDNB-NE presented a droplet size of 181.16 ± 3.20 nm and polydispersity index of 0.30 ± 0.03. MDNB and MDNB-NE inhibited the growth of all strains with minimum inhibitory concentrations of 0.27-1.10 mM. The biological results corroborated the molecular model, which pointed to a multi-target antifungal mechanism of action for MDNB in C. albicans. The study could serve as a basis for further research involving compounds with nitro groups with antifungal.

In Silico and In Vitro Evaluation of the Antifungal Activity of a New Chromone Derivative against Candida spp.

Candida species are frequently implicated in the development of both superficial and invasive fungal infections, which can impact vital organs. In the quest for novel strategies to combat fungal infections, there has been growing interest in exploring synthetic and semi-synthetic products, particularly chromone derivatives, renowned for their antimicrobial properties. In the analysis of the antifungal activity of the compound (E)-benzylidene-chroman-4-one against Candida, in silico and laboratory tests were performed to predict possible mechanisms of action pathways, and in vitro tests were performed to determine antifungal activity (MIC and MFC), to verify potential modes of action on the fungal cell membrane and wall, and to assess cytotoxicity in human keratinocytes. The tested compound exhibited predicted affinity for all fungal targets, with the highest predicted affinity observed for thymidylate synthase (-102.589 kJ/mol). MIC and CFM values ranged from 264.52 µM (62.5 µg/mL) to 4232.44 µM (1000 µg/mL). The antifungal effect likely occurs due to the action of the compound on the plasma membrane. Therefore, (E)-benzylidene-chroman-4-one showed fungicidal-like activity against Candida spp., possibly targeting the plasma membrane.

Mechanisms Involved in the Therapeutic Effect of Cannabinoid Compounds on Gliomas: A Review with Experimental Approach.

INTRODUCTION: Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several therapeutic approaches are used; however, they are associated with side effects that affect patients'quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives. OBJECTIVE: This study aimed to review the key enzymatic targets involved in glioma pathophysiology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations. METHODS: Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology. RESULTS: Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3- kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase. CONCLUSION: The evaluated compounds exhibited favorable interactions with the analyzed enzymatic targets, thus representing potential candidates for further in vitro and in vivo studies.

An In Silico Approach to Exploring the Antinociceptive Biological Activities of Linalool and its Metabolites.

Pain is characterized by the unpleasant sensory and emotional sensation associated with actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility. Among them, linalool and its metabolites stand out. The present study aims to investigate the antinociceptive potential of linalool and its metabolites through a screening using an in silico approach. Molecular docking was used to evaluate possible interactions with important targets involved in antinociceptive activity, such as α2-adrenergic, GABAergic, muscarinic, opioid, adenosinergic, transient potential, and glutamatergic receptors. The compounds in the investigated series obtained negative energies for all enzymes, representing satisfactory interactions with the targets and highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high likelihood of modulatory activity against the targets involved in nociception and are potential candidates for future drugs.

Effect of Schinus terebinthifolius on Candida albicans growth kinetics, cell wall formation and micromorphology.

OBJECTIVE: To evaluate the anti-fungal activity of a tincture from Schinus terebinthifolius (Brazilian pepper tree) on Candida albicans (ATCC 289065), a micro-organism associated with fungal infections of the oral cavity. MATERIALS AND METHODS: Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) were determined through microdilution technique, as well as the microbial growth curve of C. albicans promoted by S. terebinthifolius. In addition, this study investigated a possible activity of the product on the fungal cell wall and its biological activity on fungal morphology. Nystatin was used as control and all tests were performed in triplicate. RESULTS: S. terebinthifolius showed MIC of 312.5 µg/mL and MFC of 2500 µg/mL upon the strain tested, while Nystatin showed MIC and MFC of 6.25 µg/mL. As regards the microbial growth curve, S. terebinthifolius was able to significantly reduce the number of CFU/mL when compared to growth control until the time of 60 min. In the times 120 and 180 min there was no statistically significant difference between the growth control and the experimental product. S. terebinthifolius possibly acts on the fungal cell wall, once the sorbitol test indicated a MIC of 1250 µg/mL. In the fungal morphology, a reduction was observed of pseudo-hyphae, chlamydoconidia and blastoconidia in the presence of the experimental product. CONCLUSION: S. terebinthifolius showed anti-fungal activity against C. albicans, inhibiting, probably, the fungal cell wall formation.

Computational Studies Applied to Linalool and Citronellal Derivatives Against Alzheimer's and Parkinson's Disorders: A Review with Experimental Approach.

Alzheimer's and Parkinson's are neurodegenerative disorders that affect a great number of people around the world, seriously compromising the quality of life of individuals, due to motor and cognitive damage. In these diseases, pharmacological treatment is used only to alleviate symptoms. This emphasizes the need to discover alternative molecules for use in prevention. Using Molecular Docking, this review aimed to evaluate the anti-Alzheimer's and anti-Parkinson's activity of linalool and citronellal, as well as their derivatives. Before performing Molecular Docking simulations, the compounds' pharmacokinetic characteristics were evaluated. For Molecular Docking, 7 chemical compounds derived from citronellal, and 10 compounds derived from linalool, and molecular targets involved in Alzheimer's and Parkinson's pathophysiology were selected. According to the Lipinski rules, the compounds under study presented good oral absorption and bioavailability. For toxicity, some tissue irritability was observed. For Parkinson-related targets, the citronellal and linalool derived compounds revealed excellent energetic affinity for α-Synuclein, Adenosine Receptors, Monoamine Oxidase (MAO), and Dopamine D1 receptor proteins. For Alzheimer disease targets, only linalool and its derivatives presented promise against BACE enzyme activity. The compounds studied presented high probability of modulatory activity against the disease targets under study, and are potential candidates for future drugs.