Effectiveness of a tissue conditioner containing antifungals in a rat model of denture stomatitis.

AIM: This study investigated the effectiveness of a drug-modified tissue conditioner in an animal model of denture stomatitis. METHODS AND RESULTS: Wistar rats wore a Candida albicans-contaminated palatal device for four days. Next, nystatin (Nys) or chlorhexidine (Chx) were added to a tissue conditioner in their raw or ß-cyclodextrin-complexed (ßCD) forms at their minimum inhibitory concentrations. As controls, one group was not subjected to any procedure (NC), one group used sterile devices (SD), one group had denture stomatitis but was not treated (DS), and another had the devices relined with the tissue conditioner without the addition of any drug (Soft). After four days of treatment, treatment effectiveness was assessed visually, histologically, and through CFU count, and myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats from the Soft, Nys, Nys:ßCD, and Chx groups presented a significant decrease in the microbial load compared to the untreated group. Treatment groups showed lower MPO and NAG activity compared to the non-treated group. CONCLUSIONS: The addition of antifungals to a soft tissue conditioner can be a promising approach for denture stomatitis treatment.

Efficiency of cavitary varnishes containing experimental bioglass particles in the occlusion of dentinal tubules.

This research aims to evaluate the efficiency of cavitary varnishes containing experimental bioglasses in the occlusion of dentinal tubules. One hundred and sixty-eight cervical buccal dentin samples were obtained from bovine teeth. Samples were randomized into the following groups: I. Distilled Water (DW); II. Cavity Varnish (CV); III. Colgate® Sensitive Pro-Relief™ (CS); IV. 45S5 Bioglass (45S5); V. KSr Bioglass strontium potassium (KSr); VI. P Bioglass phosphorus (P); and VII. PSi Bioglass phosphorus silica (PSi). The treatments were applied to the surfaces of the samples, which were then subjected to simulated brushing. The samples were analyzed for a) characterization of bioactive glasses; b) surface roughness; c) descriptive analysis of the dentin surface; d) total versus occluded number of dentinal tubules; e) diameter of the dentinal tubules; f) chemical composition of the dentin surfaces, and g) dentin permeability. All groups treated with biomaterials without the brushing challenge showed an increase in roughness and (total or partial) occlusion of the dentinal tubules. The PSi group had the best values for occlusion, while the KSr group had the highest calcium and phosphorus concentrations. After the brushing challenge the roughness was controlled by the presence of biomaterials; 45S5, KSr, and PSi showed occlusion of the dentin tubules. All bioactive glasses showed reduced tooth permeability compared to distilled water. The PSi group had the smallest tubule diameter and highest phosphorus concentration. KSr and PSi bioglasses are promising materials for dentin occlusion and remineralization and are promising new biomaterials for the treatment of dentin hypersensitivity.

Anti-Candida activity and in vitro toxicity screening of antifungals complexed with ß-cyclodextrin.

The emergence of resistant fungal species and the toxicity of currently available antifungal drugs are relevant issues that require special consideration. Cyclodextrins inclusion complexes could optimize the antimicrobial activity of such drugs and create a controlled release system with few side effects. This study aimed to assess the in vitro toxicity and antifungal effectiveness of nystatin (Nys) and chlorhexidine (Chx) complexed or not with ß-cyclodextrin (ßCD). First, a drug toxicity screening was performed through the Artemia salina bioassay. Then, the minimum inhibitory concentrations (MICs) against Candida albicans were determined with the broth microdilution test. After MICs determination, the cytotoxicity of the drugs was evaluated through the methyl-thiazolyl-tetrazolium (MTT) and neutral red (NR) assays and through cell morphology analysis. The PROBIT analysis was used to determine the median lethal concentration (LC50), and the cell viability values were submitted to one-way analysis of variance(ANOVA)/Tukey (α = 0.05). Overall, the ßCD-complexed antifungals were less toxic against A. salina than their raw forms, suggesting that inclusion complexes can reduce the toxicity of drugs. The MICs obtained were as follows: Nys 0.5 mg/L; Nys:ßCD 4 mg/L; Chx 4 mg/L; and Chx:ßCD 8 mg/L. Chx showed significant cytotoxicity (MTT: 12.9 ± 9.6%; NR: 10.6 ± 12.5%) and promoted important morphological changes. Cells exposed to the other drugs showed viability above 70% with no cellular damage. These results suggest that antifungals complexed with ßCD might be a biocompatible option for the treatment of Candida-related infections.

Development of gel containing Psidium glaziovianum essential oil has in vitro antimicrobial activity and improves healing of excisional wounds in mice.

Wounds encompass physical, chemical, biological, induced damages to the skin or mucous membranes. In wound treatment, combating infections is a critical challenge due to their potential to impede recovery and inflict systemic harm on patients. Previously, the essential oil extracted from Psidium glaziovianum (PgEO) demonstrated antinociceptive and anti-inflammatory attributes, along with negligible oral toxicity. Hence, our study aimed to assess the effects of topically applying a gel formulation containing PgEO to excisional wounds in mice. Additionally, an in vitro antimicrobial assessment was conducted. The formulated gel underwent characterization and toxicological evaluation on erythrocytes, as well as a dermal irritation test. Its antimicrobial activity was tested against both gram-positive and gram-negative bacteria, as well as fungi. Subsequently, an assessment of its efficacy in excisional wound healing was conducted in mice. The findings of this investigation highlight the gel's efficacy against both gram-positive and gram-negative bacteria, as well as fungi. Moreover, this study underscores that the PgEO-gel treatment enhances skin wound healing, potentially due to its capacity to trigger antioxidant enzymes and suppress pro-inflammatory cytokines. Furthermore, the gel exhibited minimal toxicity to erythrocytes and skin irritation. These findings hold promise for prospective preclinical and clinical trials across diverse wound types. In conclusion, this study sheds light on the potential therapeutic applications of the gel formulation containing essential oil from P. glaziovianum in the context of wound healing.

Pain management in periodontal therapy using local anesthetics and other drugs: an integrative review.

Background: Surgical and non-surgical periodontal procedures often lead to postoperative pain. Clinicians use pharmacological methods such as anesthetics, anti-inflammatory drugs, and analgesics for relief. However, the multitude of options makes it challenging to select the best approach for routine dental care. Objective: This review aimed to describe previous studies regarding the pharmacological management used for pain control during periodontal procedures as well as factors that may interfere with patients' perception of pain. Methods: We included studies (period of 2000-2023, whose approach corresponded to the pharmacological protocols used for preoperative, trans-operative, and postoperative pain control in adult patients undergoing surgical and non-surgical periodontal therapy. Results: A total of 32 studies were included in the analysis, of which 17 (53%) were related to anesthetic methods and 15 (47%) were related to therapeutic protocols (anti-inflammatory/analgesic agents). These studies predominantly involved nonsurgical periodontal procedures. Studies have reported that factors related to age, type of procedure, and anxiety can influence pain perception; however, only seven of these studies evaluated anxiety. Conclusions: Numerous methods for pain control can be applied in periodontal therapy, which are accomplished through anesthetic methods and/or therapeutic protocols. Factors such as anxiety, age, and type of procedure are related to pain perception in patients. Thus, it is the responsibility of dentists to evaluate each clinical situation and define the best protocol to follow based on the literature.

COVID-19 hospitalized patients and oral changes: a case-control study.

OBJECTIVES: To investigate the association between hospitalization for COVID-19 and oral changes, and to evaluate whether oral changes can indicate a higher risk of disease progression to death. MATERIALS AND METHODS: This case-control study analyzed patients hospitalized (university hospital), including those in intensive care unit and clinical wards. The study group comprised 69 COVID-19 positive patients (PCR-test), while the control group included 43 COVID-19 negative patients. A dentist performed oral evaluations, and salivary samples were collected for calcium, phosphatase, and pH analysis. Sociodemographic data, hospitalization information, and hematological test results were collected from electronic-medical records. The presence of oral changes was assessed using chi-square tests, and the predicted risk of death was analyzed using binary logistic regression. RESULTS: COVID-19 positive patients had a significantly higher prevalence of oral changes compared to COVID-19 negative patients. The presence of any oral changes in COVID-19 positive patients indicated a 13-fold higher risk of mortality. "Bleeding ulcers," "pressure ulcers," and "angular cheilitis" were significantly associated with hospitalization for COVID-19. CONCLUSION: There may be an association between hospitalization for COVID-19 and the development of oral changes, including bleeding ulcers, pressure ulcers. and angular cheilitis. These oral changes may serve as potential indicator for disease progression an increased risk of death. CLINICAL RELEVANCE: COVID-19 hospitalized patients have a higher prevalence of oral changes, which indicate an increased risk of mortality. Oral medicine staff should be included in multidisciplinary teams to detect and treat these oral changes promptly.

Dental implants in large animal models with experimental systemic diseases: A systematic review.

This systematic review aims to identify and discuss the most used methodologies in pre-clinical studies for the evaluation of the implementation of dental implants in systemically compromised pigs and sheep. This study provides support and guidance for future research, as well as for the prevention of unnecessary animal wastage and sacrifice. Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) was used as a guideline; electronic searches were performed in PubMed, Scopus, Scielo, Web of Science, Embase, Science Direct, Brazilian Bibliography of Dentistry, Latin American and Caribbean Literature in Health Sciences, Directory of Open Access Journals, Database of Abstracts of Reviews of Effects, and gray literature until January 2022 (PROSPERO/CRD42021270119). Sixty-eight articles were chosen from the 2439 results. Most studies were conducted in pigs, mainly the Göttinger and Domesticus breeds. Healthy animals with implants installed in the jaws were predominant among the pig studies. Of the studies evaluating the effect of systemic diseases on osseointegration, 42% were performed in osteoporotic sheep, 32% in diabetic sheep, and 26% in diabetic pigs. Osteoporosis was primarily induced by bilateral ovariectomy and mainly assessed by X-ray densitometry. Diabetes was induced predominantly by intravenous streptozotocin and was confirmed by blood glucose analysis. Histological and histomorphometric analyses were the most frequently employed in the evaluation of osseointegration. The animal models presented unique methodologies for each species in the studies that evaluated dental implants in the context of systemic diseases. Understanding the most commonly used techniques will help methodological choices and the performance of future studies in implantology.

Prevalence of dentin hypersensitivity after orthodontic treatment: A cross-sectional study.

INTRODUCTION: The prevalence of cervical dentin hypersensitivity in patients after corrective orthodontic treatment has been poorly studied, although such hypersensitivity is very common. This study aimed to assess the prevalence of dentin hypersensitivity in patients who received corrective orthodontic treatment, the impact of general oral problems on quality of life, and the impact of hypersensitivity on the quality of life of this population. METHODS: This observational, cross-sectional study evaluated 232 patients who finished orthodontic treatment between 2000 and 2020 for self-reported hypersensitivity and clinically diagnosed hypersensitivity. The following tests were used: tactile, evaporative (bellows), evaporative (triple syringe), and thermal. The patients were also evaluated regarding their quality of life using questionnaires (Oral Health Impact Profile-14 and Dentine Hypersensitivity Experience Questionnaire). We evaluated data with nonparametric statistics. RESULTS: The prevalence of hypersensitivity was higher in women and in those aged <30 years; the most affected teeth were the mandibular incisors and premolars; different diagnostic tests for hypersensitivity may indicate different prevalence values; patients with hypersensitivity had a lower quality of life in most of the domains of both of the tests that were used. CONCLUSIONS: The prevalence of hypersensitivity among patients after orthodontic treatment may be higher than in the general population. Further investigation is needed to indicate the possible factors associated with orthodontic tooth movement.

Impact of evidence-based bundles on ventilator-associated pneumonia prevention: A systematic review.

INTRODUCTION: This review aimed at investigating the impact of bundle components on the prevention of ventilator-associated pneumonia (VAP) in adults and the elderly. METHODOLOGY: The databases consulted were PubMed, EBSCO, and Scielo. The terms Bundle and Pneumonia were searched in combination. The original articles were selected in Spanish and English; published between January 2008 and December 2017. After eliminating the duplicate papers, an analysis of the titles and the abstracts was performed in order to select the assessed articles. A total of 18 articles were included in this review that were evaluated according to the following criteria: research reference, country of data collection, type of study, characteristics of the studied patients, analysis and intervention performed, bundle items investigated and their results, and research outcome. RESULTS: Four bundle items were presented in all the investigated papers. 61% of those works were considered from seven to eight bundle items. Daily evaluation of sedation interruption and daily assessment for verifying extubation condition, head-of-bed elevation at 30 degrees, cuff pressure monitoring, coagulation prophylaxis, and oral hygiene were the most reported bundle items. One study described the increased mortality of patients under mechanical ventilation when omitted the bundle items of oral hygiene and stress ulcer prophylaxis. Head-of-bed elevation at 30 degrees was the item reported in 100% of the studied papers. CONCLUSIONS: Existing research demonstrated that VAP reduction occurred when bundle items were performed for adults and the elderly. Four works showed the relevance of team education as a central approach to the event reduction related to the ventilator.

In vitro evaluation of alkaline lignins as antiparasitic agents and their use as an excipient in the release of benznidazole.

The Amazon rainforest is considered the largest tropical timber reserve in the world. The management of native forests in the Amazon is one of the most sensitive geopolitical issues today, given its national and international dimension. In this work, we obtained and characterized physicochemical lignins extracted from branches and leaves of Protium puncticulatum and Scleronema micranthum. In addition, we evaluated in vitro its potential as an antioxidant, cytotoxic agent against animal cells and antiparasitic against promastigotes of Leishmania amazonensis, trypomastigotes of T. cruzi and against Plasmodium falciparum parasites sensitive and resistant to chloroquine. The results showed that the lignins obtained are of the GSH type and have higher levels of guaiacyl units. However, they show structural differences as shown by spectroscopic analysis and radar charts. As for biological activities, they showed antioxidant potential and low cytotoxicity against animal cells. Antileishmanial/trypanocidal assays have shown that lignins can inhibit the growth of promastigotes and trypomastigotes in vitro. The lignins in this study showed low anti-Plasmodium falciparum activity against susceptible strains of Plasmodium falciparum and were able to inhibit the growth of the chloroquine-resistant strain. And were not able to inhibit the growth of Schistosoma mansoni parasites. Finally, lignins proved to be promising excipients in the release of benznidazole. These findings show the potential of these lignins not yet studied to promote different biological activities.

A novel rat model of denture stomatitis and the role of antibiotics in the development of the disease.

This study compared different conditions to establish a rat model of denture stomatitis. Immunocompetent Wistar rats were divided into two groups (n = 35): Tetracycline = administration of 0.83 mg/ml of tetracycline hydrochloride 7 days before induction of denture stomatitis and amoxicillin = administration of 0.156 mg/ml of amoxicillin with clavulanic acid 4 days before induction of denture stomatitis. A suspension of Candida albicans was inoculated on the palate followed by the use of a palatal device contaminated with C. albicans inoculum for 4 days to induce denture stomatitis. As controls, some rats were not submitted to any procedure or used a sterile palatal device for 4 days. The development of denture stomatitis was confirmed by visual analysis, colony-forming units per milliliter (CFU/ml) count, histopathological and immunohistochemical analyses, and through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats were euthanized right after device removal (T0), 4 (T4), or 6 (T6) days after device removal. Tetracycline improved the development of the disease, with more severe clinical signs at T0. Similar results were observed in the CFU/ml count and in the histometric and immunohistochemical analyses. Higher MPO expression was detected in the palates of the tetracycline group (P = .006). Despite the subtle differences between antibiotics, tetracycline showed better results in inducing and maintaining denture stomatitis for at least 4 days after device removal.

Denture stomatitis is an oral inflammatory disease with high recurrence rates. Different animal models have been reported in the literature, but some gaps still need to be addressed. A reproducible in vivo model should be established to test new treatment approaches.

Brown spider (Loxosceles sp.) bite and COVID-19: A case report.

We present the case of a 32-year-old male patient hospitalized during the COVID-19 pandemic because of a Brown spider bite on his lower lip. The Brown spider accident occurred in southern Brazil; at hospital admission, the patient presented on his lip: edema, pustules, necrotic regions, and ulcerations. The patient complained of lower back pain, fever and dyspnea. Laboratory tests showed monocytosis, leukocytosis, neutrophilia, increased D-dimer levels, C-reactive protein, glutamate-pyruvate transaminase, delta bilirubin, creatine phosphokinase, procalcitonin, and fibrinogen. The patient was hospitalized and a multi-professional team carried out the treatment. The medical team diagnosed loxoscelism with moderate changes. The dentist treated the oral cavity. The patient began to develop nausea, vomiting, and desaturation episodes during hospitalization. A computed tomography of the chest was performed, which showed signs of viral infection. The RT-PCR test for COVID-19 was positive. The systemic conditions worsened (renal dysfunction, systemic inflammatory response, pulmonary complications). This condition may have resulted from the association of the two diseases (loxoscelism and COVID-19), leading to the patient's death. This case illustrates the difficulties and risks in treating patients with venomous animal accidents during the pandemic, and the importance of a multi-professional team in treating such cases.

Myeloperoxidase as an important predictor of cardiovascular risk in individuals with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is an inflammatory disease with joint manifestations. In the presence of extra-articular manifestations, the morbidity and severity of the disease increase. Glucocorticoid is used as a treatment and may result in side effects related to cardiovascular risk. METHODS: This was a cross-sectional study including 59 volunteers with rheumatoid arthritis receiving treatment at a hospital of Campos Gerais that aimed to establish the relation between cardiovascular risk, glucocorticoid treatment and myeloperoxidase in these patients. Subjects were divided into two groups: using (n = 39) and without glucocorticoids (n = 20). They underwent clinical evaluation, physical examination and blood samples were taken. Statistical analysis was performed using Student's t test and Mann-Whitney test. Logistic regression was performed to assess the cardiovascular risk. The significance level was 5% (α = 0.05). Calculations were performed using the Statistical Package for the Social Science version 21.0. RESULTS: There has been a significant difference between groups in blood glucose values (p = 0.012), which can be explained by the different percentage of diabetic patients in the groups. When assessing cardiovascular risk using the predictors of glucocorticoid dose, time of glucocorticoid use, myeloperoxidase, and C-reactive protein together, these were responsible for significantly predicting this risk (p = 0.015). CONCLUSION: A significant relation between the predictor myeloperoxidase alone was also demonstrated (p = 0.037), it may be an important predictor of cardiovascular risk among individuals with rheumatoid arthritis.

Lignin from Morinda citrifolia leaves: Physical and chemical characterization, in vitro evaluation of antioxidant, cytotoxic, antiparasitic and ultrastructural activities.

In this work, we investigated in vitro the antioxidant, cytotoxic and anti-leishmanial activities of a lignin extracted from the leaves of Morinda citrifolia. Initially, an analysis of the composition of the sheets was performed, then the lignin was obtained by alkaline delignification and characterized by different techniques: elemental analysis, FT-R, UV-vis, HSQC-NMR, thermal analysis, Py-GC/MS and by GPC. The results showed that the leaves had in their composition cellulose (31.29%), hemicellulose (25.01%), lignin (18.34%), extractives (14.39%) and ash (10.03%). The lignin extraction yield was 89.8%. The lignin obtained is of the GSH type with the following contents 79.39%, 13.58% and 7.03% respectively. Furthermore, it is low molecular weight and thermally stable. It had a phenolic content of 93.3 mg GAE/g and low antioxidant activity. In macrophage cytotoxicity assays, it presented a CC50 of 31.0 µg/mL, showing less toxicity than amphotericin B. In assays against the promastigote forms of Leishmania amazonensis, lignin presented an IC50 of 29.56 µg/mL, a less effective concentration than amphotericin B (IC50 = 0.14 µg/mL). However, it was able to promote inhibition of the parasites, a fact confirmed by structural changes. These findings reinforce that M. citrifolia lignin is a promising macromolecule for use as an antiparasitic and antioxidant agent.

Use of non-invasive intracranial pressure pulse waveform to monitor patients with End-Stage Renal Disease (ESRD).

End-stage renal disease (ESRD) is treated mainly by hemodialysis, however, hemodialysis is associated with frequent complications, some of them involve the increased intracranial pressure. In this context, monitoring the intracranial pressure of these patients may lead to a better understanding of how intracranial pressure morphology varies with hemodialysis. This study aimed to follow-up patients with ESRD by monitoring intracranial pressure before and after hemodialysis sessions using a noninvasive method. We followed-up 42 patients with ESRD in hemodialysis, for six months. Noninvasive intracranial pressure monitoring data were obtained through analysis of intracranial pressure waveform morphology, this information was uploaded to Brain4care® cloud algorithm for analysis. The cloud automatically sends a report containing intracranial pressure parameters. In total, 4881 data points were collected during the six months of follow-up. The intracranial pressure parameters (time to peak and P2/P1 ratio) were significantly higher in predialysis when compared to postdialysis for the three weekly sessions and throughout the follow-up period (p<0.01) data showed general improvement in brain compliance after the hemodialysis session. Furthermore, intracranial pressure parameters were significantly higher in the first weekly hemodialysis session (p<0.05). In conclusion, there were significant differences between pre and postdialysis intracranial pressure in patients with ESRD on hemodialysis. Additionally, the pattern of the intracranial pressure alterations was consistent over time suggesting that hemodialysis can improve time to peak and P2/P1 ratio which may reflect in brain compliance.

Chemical composition, antimicrobial activity and synergistic effects with conventional antibiotics under clinical isolates by essential oil of Hymenaea rubriflora Ducke (FABACEAE).

This work aimed to investigate the chemical composition, antimicrobial activity, synergistic effect, and structure changes of the essential oil of Hymenaea rubriflora (EOHr). Forty-five constituents were identified in the essential oil, corresponding to 94.43% of the compounds present, being the main components E-Caryophyllene (36.72 ± 1.05%), Germacrene D (16.13 ± 0.31%), α-Humulene (6.06 ± 0.16%), ß-elemene (5.61 ± 0.14%) and δ-Cadinene (3.76 ± 0.07%). Antimicrobial activity was evaluated, presenting antibacterial and antifungal activity with MIC ranging from 0.62 to 40 µL/mL. The essential oil had a synergistic effect when combined with gentamicin and fluconazole. Structural changes were also evaluated and it was possible to observe that EOHr action was related to changes in membrane permeability. The findings obtained here suggest that the use of the essential oil of H. rubriflora in the treatment of infectious diseases presents a potential for the future development of pharmaceutical products.

Caloric restriction prevents alveolar bone loss in the experimental periodontitis in obese rats.

AIMS: It has been shown that periodontitis, can be modified by systemic changes, including behavioral factors, such as diet. Caloric restriction is one of the dietary therapeutic strategies indicated for obesity. It is associated with several benefits, among them, modulation of the inflammatory response. The aim of this study was to verify whether caloric restriction in obese rats changes the progression of experimental ligature-induced periodontitis. MATERIALS AND METHODS: Forty-eight Wistar rats were used for 24 weeks and initially fed with cafeteria diet during 12 weeks. The animals were divided into four groups according to the caloric restriction and experimental periodontitis. The cotton thread was placed around the mandibular first molars, for 15 days, before the end of the experiment. Rats submitted to caloric restriction received, from the 13th week of the experimental protocol, 70% of the food intake compared to the ad libitum animals of other study of the our research group. Alveolar bone loss was assessed using macroscopic morphometric analysis. Analyzes of clinical periodontal measures, biometrics, serum biomarkers and biochemical parameters were performed. KEY FINDINGS: Caloric restriction decreased the alveolar bone loss in the periodontitis group when compared to the group that received a cafeteria diet with periodontitis. Moreover, the results demonstrate the improvement in the glycemic profile, without prejudice to bone tissue biomarkers. SIGNIFICANCE: Based on the results, caloric restriction reduces the progression of alveolar bone loss in rats with experimental periodontitis, in addition to presenting benefits in biometric data, decreasing both glycemic profile and clinical periodontal measures.

Novel indol-3-yl-thiosemicarbazone derivatives: Obtaining, evaluation of in vitro leishmanicidal activity and ultrastructural studies.

Parasitic diseases still represent serious public health problems, since the high and steady emergence of resistant strains is evident. Because parasitic infections are distributed predominantly in developing countries, less toxic, more efficient, safer and more accessible drugs have become desirable in the treatment of the infected population. This is the case of leishmaniasis, an infectious disease caused by a protozoan of the genus Leishmania sp., responsible for triggering pathological processes from the simplest to the most severe forms leading to high rates of morbidity and mortality throughout the world. In the search for new leishmanicidal drugs, the thiosemicarbazones and the indole fragments have been identified as promising structures for leishmanicidal activity. The present study proposes the synthesis and structural characterization of new indole-thiosemicarbazone derivatives (2a-j), in addition to performing in vitro evaluations through cytotoxicity assays using macrophages (J774) activity against forms of Leishmania infantum and Leishmania amazonensis promastigote as well as ultrastructural analyzes in promastigotes of L. infantum. Results show that the indole-thiosemicarbazone derivatives were obtained with yield values varying from 32.09 to 94.64%. In the evaluation of cytotoxicity, the indole-thiosemicarbazone compounds presented CC50 values between 53.23 and 357.97 µM. Concerning the evaluation against L. amazonensis promastigote forms, IC50 values ranged between 12.31 and  > 481.52 µM, while the activity against L. infantum promastigotes obtained IC50 values between 4.36 and 23.35 µM. The compounds 2d and 2i tested against L. infantum were the most promising in the series, as they showed the lowest IC50 values: 5.60 and 4.36 respectively. The parasites treated with the compounds 2d and 2i showed several structural alterations, such as shrinkage of the cell body, shortening and loss of the flagellum, intense mitochondrial swelling and vacuolization of the cytoplasm leading the parasite to cellular unviability. Therefore, the indole-thiosemicarbazone compounds are promising because they yield considerable synthesis, have low cytotoxicity to mammalian cells and act as leishmanicidal agents.

New 1,3-benzodioxole derivatives: Synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis.

Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3-14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 µM and 83.3% at the concentration of 50 µM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs.