Anticonvulsant and anxiolytic-like potential of the essential oil from the Ocimum basilicum Linn leaves and its major constituent estragole on adult zebrafish (Danio rerio).

The Ocimum species present active compounds with the potential to develop drugs for treating chronic disease conditions, such as anxiety and seizures. The present study aims to investigate the anticonvulsant and anxiolytic-like effect of the essential oil from O. basilicum Linn (OEFOb) leaves and its major constituent estragole (ES) in vivo on adult zebrafish (aZF) and in silico. The aZF were treated with OEFOb or ES or vehicle and submitted to the tests of toxicity, open-field, anxiety, and convulsion and validated the interactions of the estragole on the involvement of GABAergic and serotonergic receptors by molecular docking assay. The results showed that the oral administration of OEFOb and ES did not have a toxic effect on the aZF and showed anxiolytic-like effects with the involvement of GABAA, 5-HT1, 5-HT2A/2C and 5-HT3A/3B as well on anxiety induced by alcohol withdrawal. The OEFOb and ES showed anticonvulsant potential attenuating the seizures induced by pentylenetetrazole (PTZ) by modulation of the GABAA system. Both anxiolytic and anticonvulsant effects were corroborated by the potential of the interaction of ES by in silico assay. These study samples demonstrate the pharmacological evidence and potential for using these compounds to develop new anxiolytic and anticonvulsant drugs.

Phase angle as an indicator of body composition and physical performance in handball players.

BACKGROUND: Phase angle (PhA), obtained from the bioimpedance analysis, is widely used in clinical situations and in sports. This study evaluated the association between PhA with body composition and physical performance of handball athletes. METHODS: 43 national-level players (22.19 ± 3.86 years) of both sexes were evaluated regarding anthropometry, body composition, squat (SJ) and countermovement (CMJ) jumps, handgrip strength, and cardiorespiratory fitness. RESULTS: We verified a correlation between PhA of the whole body and fat-free mass (r = 0.511), body mass index (r = 0.307), and body fat % (r = -0.303). There was a positive correlation between PhA of the whole body and SJ (r = 0.376), CMJ (r = 0.419), and handgrip for the dominant hand (r = 0.448). Moreover, PhA of the upper limbs was more strongly correlated with handgrip for the dominant (r = 0.630) and non-dominant hand (r = 0.575) compared to PhA of the whole body considering both sexes. Similarly, segmental PhA had a stronger significant correlation with SJ (r = 0.402) and handgrip for the dominant hand (r = 0.482) in males, as well as CMJ (r = 0.602) in females, compared to PhA of the whole body. CONCLUSION: PhA of the whole body was positively related to fat-free mass, body mass index, body fat %, and lower- and upper-limbs strength in handball athletes. Segmental PhA might be used as a tool for estimating lower and upper limbs performance considering the sex, in preference to the PhA of the whole body.

Potential of the Blue Calm® food supplement in the treatment of alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio).

Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents. In this context, this study aimed to evaluate the potential of the BC in the treatment alcohol withdrawal-induced anxiety in adult zebrafish (aZF). Initially, BC was submitted to antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl radical. Subsequently, the aZF (n = 6/group) were treated with BC (0.1 or 1 or 10 mg/mL; 20 µL; p.o.), and the sedative effect and acute toxicity (96 h) were evaluated. Then, the anxiolytic-like effect and the possible GABAergic mechanism were analyzed through the Light & Dark Test. Finally, BC action was evaluated for treating alcohol withdrawal-induced anxiety in aZF. Molecular docking was performed to evaluate the interaction of the major chemical constituents of BC with the GABAA receptor. BC showed antioxidant potential, a sedative effect, was not toxic, and all doses of BC had an anxiolytic-like effect and showed potential for the treatment of alcohol withdrawal-induced anxiety in aZF. In addition to the anxiolytic action, the main chemical constituents of BC were confirmed in the molecular docking, thus suggesting that BC is an anxiolytic that modulates the GABAergic system and has pharmacological potential for the treatment of alcohol withdrawal-induced anxiety.

Antibacterial activity and anxiolytic-like effect of Ziziphus joazeiro Mart. leaves in adult zebrafish (Danio rerio).

Ziziphus joazeiro Mart. is an endemic plant of the Caatinga that presents a great socioeconomic importance for the Northeast and Semiarid Region of Brazil. In view of this, this study aimed to evaluate the antibacterial activity and anxiolytic-like effects of Ziziphus joazeiro Mart leaves in adult zebrafish (Danio rerio). The characterization of the main classes of metabolites was performed through chemical reactions. The antibacterial and antibiotic potentiating activity was evaluated by broth microdilution assays. The 96 h acute toxicity, open field test and anxiety models test was evaluated in vivo on adult zebrafish. The results obtained in the phytochemical prospection evidenced the presence of flobabenic tannins, leucoanthocyanidins, flavonois, flavonones, catechins, alkaloids, steroids, and triterpenoids. EEFZJ did not show antibacterial activity for all microorganism tested (MIC ≥ 1024 µg/mL), but reduced the concentration required for bacterial growth inhibition in combination with gentamicin and norfloxacin against multidrug-resistant strains of S. aureus (SA10) and E. coli (EC06), exhibiting synergistic effect with these antibiotics (p<0.0001). In the tests in vivo, EEFZJ was found to be nontoxic, performing reduced locomotor activity and demonstrated an anxiolytic-like effect in adult zebrafish via GABAergic and Serotoninergic systems (5-HT1, 5-HT2A/2C and 5-HT3A/3B).

Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.

BACKGROUND: Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality. METHODS: A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis. RESULTS: Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients. CONCLUSIONS: ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.

CA 15-3, CRP, and LDH correlates with prognostic parameters in canine mammary neoplasms.

The identification of putative prognostic factors in canine mammary neoplasms (CMNs) has been focused on tissue-specific biomarkers, but the serum biomarkers, including cancer antigen 15-3 (CA 15-3), c-reactive protein (CRP), and lactate dehydrogenase (LDH) have been demonstrated to display clinical application in cases of CMNs. The aim of the study was to evaluate the levels of these serum biomarkers and their association with well-established prognostic factors in CMNs. Samples from 15 female canines with CMNs and 15 clinically healthy ones were collected. The results were evaluated using the Tukey's, Pearson, or Spearman tests. The cut-off point, sensitivity, specificity, and area under curve (AUC) were evaluated using the receiver operating characteristic (ROC) curve analysis in a logistic regression model (P<0.05). The levels of CA 15-3, CRP and LDH were significantly higher in the serum of female dogs with CMNs compared to the healthy ones. Moreover, these factors were positively correlated with ulceration, tumor size, histopathological grade, metastatic lymph node, and clinical staging. Female dogs with CMNs were found to exhibit highest serum levels of CA 15-3, CRP, and LDH. Therefore, they can be applied to improve the efficacy of the diagnosis and prognostic evaluation in casas of CMNs.

Pharmacological Potential of cis-jasmone in Adult Zebrafish (Danio rerio).

This study evaluates the pharmacological potential of cis-jasmone (CJ) in adult zebrafish (Danio rerio; aZF). Initially, aZF (n = 6/group) were pretreated (20 µL; p. o.) with CJ (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.5% Tween 80). The animals were submitted to acute toxicity and locomotion tests, pentylenetetrazole-induced seizure, carrageenan-induced abdominal edema, and cinnamaldehyde-, capsaicin-, menthol-, glutamate-, and acid saline-induced orofacial nociception. The possible mechanisms of anticonvulsant, anxiolytic, and antinociceptive action were evaluated. The involvement of central afferent fibers sensitive to cinnamaldehyde and capsaicin and the effect of CJ on the relative gene expression of TRPA1 and TRPV1 in the brain of aZF were also analyzed, in addition to the study of molecular docking between CJ and TRPA1, TRPV1 channels, and GABAA receptors. CJ did not alter the locomotor behavior and showed pharmacological potential in all tested models with no toxicity. The anticonvulsant effect of CJ was prevented by flumazenil (GABAergic antagonist). The anxiolytic-like effect of CJ was prevented by flumazenil and serotonergic antagonists. The antinociceptive effect was prevented by TRPA1 and TRPV1 antagonists. Chemical ablation with capsaicin and cinnamaldehyde prevented the orofacial antinociceptive effect of CJ. Molecular docking studies indicate that CJ interacted with TRPA1, TRPV1, and GABAA receptors. CJ inhibited the relative gene expression of TRPA1 and TRPV1. CJ has pharmacological potential for the treatment of seizures, anxiety, inflammation, and acute orofacial nociception. These effects are obtained by modulating the GABAergic and serotonergic systems, as well as the TRPs and ASIC channels.

Vivências dos familiares sobre a hospitalização de crianças em uma unidade de terapia intensiva pediátrica / Experiences of families on children's hospitalization in a pediatric intensive care unit / Experiencias de familiares sobre la hospitalización de niños en una unidad de terapia intensiva pediátrica

Objetivo: compreender a vivência dos familiares sobre a hospitalização da criança na perspectiva do cuidado humanizado. Métodos: pesquisa descritiva, caracterizada por abordagem qualitativa. O estudo foi realizado na Unidade de Terapia Intensiva Pediátrica do Hospital Municipal de Imperatriz, no estado do Maranhão. Participaram da pesquisa 10 familiares de crianças que estavam internadas por no mínimo 72 horas. As informações foram coletadas mediante a entrevista semiestruturada, no mês de novembro de 2019. Utilizou-se a análise do conteúdo na modalidade temática para tratamento dos dados. Resultados: emergiram quatro categorias: Sentimentos dos familiares diante da hospitalização da criança; Dificuldades enfrentadas pelas famílias durante o período de internação da criança; Cuidado Humanizado; e Estratégias de Enfrentamento dos familiares relacionados à hospitalização da criança. Conclusão: Constatou-se que os familiares vivenciam sentimentos de tristeza diante da hospitalização da criança na Unidade de Terapia Intensiva Pediátrica e desconhecem o significado de cuidado humanizado, associando-o com o fato de estarem sendo bem acolhidos. (AU)

Objective: to understand the experience of family members about the hospitalization of the child from the perspective of humanized care. Methods: descriptive and exploratory research, characterized by a qualitative approach. The study was carried out in the Pediatric Intensive Care Unit of the Municipal Hospital of Imperatriz, in the state of Maranhão. Ten relatives of children who were hospitalized for at least 72 hours participated in the study. The information was collected through the semi-structured interview in November 2019. Content analysis was used in the thematic modality for data processing. Results: four categories emerged: Feelings of family members regarding the hospitalization of the child; Difficulties faced by families during the child's hospitalization period; Humanized Care; and Strategies to cope with family members related to the hospitalization of the child. Conclusion: It was found that family members experience feelings of sadness before the child's hospitalization in the Pediatric Intensive Care Unit and were unaware of the meaning of humanized care, associating it with the fact that they are being welcomed. (AU)

Objetivo: entender la experiencia de los miembros de la familia sobre la hospitalización del niño desde la perspectiva de la atención humanizada. Métodos: investigación descriptiva y exploratoria, caracterizada por un enfoque cualitativo. El estudio se llevó a cabo en la Unidad de Cuidados Intensivos Pediátricos del Hospital Municipal de Imperatriz, en el estado de Maranhao. Diez familiares de niños que fueron hospitalizados durante al menos 72 horas participaron en el estudio. La información fue recopilada a través de la entrevista semiestructurada en noviembre de 2019. El análisis de contenido se utilizó en la modalidad temática para el procesamiento de datos. Resultados: surgieron cuatro categorías: Sentimientos de los miembros de la familia con respecto a la hospitalización del niño; Dificultades a las que se enfrentan las familias durante el período de hospitalización del niño; Cuidado Humanizado; y Estrategias para hacer frente a los miembros de la familia relacionados con la hospitalización del niño. Conclusión: Se encontró que los familiares experimentan sentimientos de tristeza ante la internación del niño en la Unidad de Cuidados Intensivos Pediátricos y desconocen el significado del cuidado humanizado, asociándolo al hecho de que están siendo bienvenido. (AU)

Systematic review with network meta-analysis on the treatments for latent tuberculosis infection in children and adolescents.

BACKGROUND: We aimed to synthesize the evidence on the efficacy and safety of different treatment regimens for latent tuberculosis infection (LTBI) in children and adolescents. METHODS: A systematic review with network meta-analysis was performed (CRD142933). Searches were conducted in Pubmed and Scopus (Nov-2021). Randomized controlled trials comparing treatments for LTBI (patients up to 15 years), and reporting data on the incidence of the disease, death or adverse events were included. Networks using the Bayesian framework were built for each outcome of interest. Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Rank probabilities were calculated via the surface under the cumulative ranking analysis (SUCRA) (Addis-v.1.16.8). GRADE approach was used to rate evidence's certainty. RESULTS: Seven trials (n = 8696 patients) were included. Placebo was significantly associated with a higher incidence of tuberculosis compared to all active therapies. Combinations of isoniazid (15-25 mg/kg/week) plus rifapentine (300-900 mg/week), followed by isoniazid plus rifampicin (10 mg/kg/day) were ranked as best approaches with lower probabilities of disease incidence (10% and 19.5%, respectively in SUCRA) and death (20%). Higher doses of isoniazid monotherapy were significantly associated to more deaths (OR 18.28, 95% ICr [1.02, 48.60] of 4-6 mg/kg/day vs. 10 mg/kg/3x per week). CONCLUSIONS: Combined therapies of isoniazid plus rifapentine or rifampicin for short-term periods should be used as the first-line approach for treating LTBI in children and adolescents. The use of long-term isoniazid as monotherapy and at higher doses should be avoided for this population.

Transient receptor potential channel involvement in antinociceptive effect of citral in orofacial acute and chronic pain models.

This study aimed to test for the possible antinociceptive effect of the naturally occurring terpene citral in rodent models of acute and chronic orofacial pain and to test for the possible involvement of transient receptor potential (TRP) channels in this effect. Acute nociceptive behavior was induced in one series of experiments by administering formalin, cinnamaldehyde, menthol or capsaicin to the upper lip. Nociceptive behavior was assessed by orofacial rubbing, and the effects of pre-treatment with citral (0.1, 0.3 or 1.0 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint or mustard oil injected into the masseter muscle, preceded by citral or vehicle (control) treatment. The chronic pain model involved infraorbital nerve transection (IONX) that induced mechanical hypersensitivity which was assessed by von Frey hair stimulation of the upper lip. Motor activity was also evaluated. Docking experiments were performed using TRPV1 and TRPM8 channels. Citral but not vehicle produced significant (p<0.01, ANOVA) antinociception on all the acute nociceptive behaviors, and these effects were attenuated by TRPV1 antagonist capsazepine, TRPM3 antagonist mefenamic acid and by TRPM8 desensitization, but not by ruthenium red and TRPA1 antagonist HC-030031. The IONX animals developed facial mechanical hypersensitivity that was significantly reduced by citral but not by vehicle. The docking experiments revealed that citral may interact with TRPV1 and TRPM8 channels. These results indicate the potential use of citral as an inhibitor of orofacial nociception in both acute and chronic pain states through TRPV1, TRPM3 and TRPM8 channels. See also Figure 1(Fig. 1).

Development of a Nanoformulation for Oral Protein Administration: Characterization and Preclinical Orofacial Antinociceptive Effect.

Nanoencapsulation is a valid alternative for the oral administration of peptide drugs and proteins, as nanoparticles protect them from proteolytic degradation in the gastrointestinal tract and promote the absorption of these macromolecules. The orofacial antinociceptive effect of frutalin (FTL), through the intraperitoneal route, has already been proven. This study aimed to develop, characterize, and evaluate the orofacial antinociceptive activity of an oral formulation containing FTL in acute and neuropathic preclinical tests. Nanoencapsulated FTL was administered by oral route. The acute nociceptive behavior was induced by administering capsaicin to the upper lip and NaCl to the right cornea. The nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The neuropathic pain model involved infraorbital nerve transection (IONX), which induced mechanical hypersensitivity and was assessed by von Frey stimulation. Trpv1 gene expression was analyzed in the trigeminal ganglion. The analyzed sample did not show any cytotoxicity; 52.2% of the FTL was encapsulated, and the size of the nanocapsule was less than 200 nm, the polydispersion was 0.361, and the zeta potential was - 5.87 and - 12.8 mV, with and without FTL, respectively. Nanoencapsulated FTL administered by oral route had an orofacial antinociceptive effect in acute and neuropathic rodent models. The antinociceptive effect of FTL was prevented by ruthenium red, but not by camphor. FTL reduced Trpv1 gene expression. FTL promotes orofacial antinociception, probably due to the antagonism of TRPV1 channels, and the nanoformulation represents an effective method for the oral administration of this protein. HIGHLIGHTS: • Nanoformulation for oral protein administration. • Nanocapsule containing FTL prevents orofacial nociceptive acute and neuropathic pain. • Frutalin promotes orofacial antinociception behavior antagonism of TRPV1 channels.

Padronização de uma PCR multiplex para a detecção de fraude em leite bubalino e caprino por adição de leite bovino / Standardization of a multiplex PCR for detection of fraud in buffalo and goat milk by addition of bovine milk

O consumo de leite de espécies como bubalino e caprino tem se popularizado por representarem uma alternativa para indivíduos que possuem restrições alimentares relacionadas ao leite bovino e em virtude das propriedades nutricionais desses alimentos. No entanto, fatores como a baixa produção e a sazonalidade predispõem a adulterações destes alimentos, principalmente pela adição de leite bovino, visando maior rendimento e lucratividade. Assim, o objetivo do estudo foi padronizar um método de PCR multiplex para autenticação de leites bubalino e caprino. Para isso, amostras de leite exclusivamente de cada espécie foram utilizados para a padronização da técnica. Em seguida, foi realizada a fraude pela adição de leite bovino ao caprino e ao bubalino, em proporções de 0,1% até 100%. A técnica foi eficaz, precisa, rápida e prática para a detecção do DNA de bovino, bubalino e caprino, separadamente e em conjunto. Na fraude experimental, o limite de detecção da técnica ocorreu a partir do menor percentual testado (0,1%) tanto no leite caprino quanto no bubalino. Dessa forma, a PCR multiplex testada mostrou ser uma importante ferramenta para a autenticação de leite, pendendo ser utilizada para fins de fiscalização por órgãos competentes.

Milk consumption of species such as buffalo and goat has become popular due to the nutritional properties of these foods and because they represent an alternative for individuals who have dietary restrictions related to bovine milk. However, factors such as low production and seasonality predispose to adulteration, mainly by the addition of bovine milk, aiming at higher yield and profitability. Thus, the aim of the present study was to standard a multiplex PCR method for buffalo and goat milks authentication. For this, the milks exclusively of each species were used to standardize the technique. Subsequently, fraud was performed by the addition of bovine milk to goat and buffalo in proportions from 0.1% to 100%. The technique was effective and accurate for detecting bovine, buffalo and goat DNA separately and together quickly and practically. In experimental fraud, the detection limit of the technique occurred from the lowest percentage tested (0.1%) in both goat and buffalo milk. Thus, the multiplex PCR tested proved to be an important tool for milk authentication, pending to be used for supervision by competent agencies.

Rapid and selective detection of dopamine in human serum using an electrochemical sensor based on zinc oxide nanoparticles, nickel phthalocyanines, and carbon nanotubes.

Composite materials have gained significant attention owing to the synergistic effects of their constituent materials, thereby facilitating their utilization in new applications or in improving the existing ones. In this study, a composite based on nickel phthalocyanine (NiTsPc), zinc oxide nanoparticles (ZnONPs), and carbon nanotubes (CNT) was developed and subsequently immobilized on a pyrolytic graphite electrode (PGE). The PGE/NiTsPc-ZnONPs-CNT was identified as a selective catalytic hybrid system for detection of neurotransmitter dopamine (DA). The electrochemical and morphological characterizations were conducted using atomic force microscopy (AFM). Chronoamperometry and differential pulse voltammetry (DPV) were used to detect DA and detection limits of 24 nM and 7.0 nM was found, respectively. In addition, the effects of some possible DA interferents, such as ascorbic acid, uric acid, and serotonin, on DA response were evaluated. Their presence did not show significant variations in the DA electrochemical response. The high specificity and sensitivity of PGE/NiTsPc-ZnONPs-CNT for DA enabled its direct detection in human serum without sample pretreatment as well as in DA-enriched serum samples, whose recovery levels were close to 100%, thereby confirming the effectiveness of the proposed method. In general, PGE/NiTsPc-ZnONPs-CNT is a promising candidate for future applications in clinical diagnosis.

Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation.

Objectives: This study aimed to develop a piperacillin population PK model for critically ill Brazil-ian patients and describe interethnic variation using an external validation. Methods: Plasma samples were obtained from 24 ICU patients during the fifth day of piperacillin treatment and assayed by HPLC-UV. Population pharmacokinetic modelling was conducted using Pmetrics. Empiric dose of 4 g IV 6- and 8-hourly were simulated for 50 and 100% fT > MIC and the probabil-ity of target attainment (PTA) and the fractional target attainment (FTA) determined. Results: A two-compartment model was designed to describe the pharmacokinetics of critically ill Brazillian patients. Clearance and volume of distribution were (mean ± SD) 3.33 ± 1.24 L h−1 and 10.69 ± 4.50 L, respectively. Creatinine clearance was positively correlated with piperacillin clearance and a high creatinine clearance was associated with lower values of PTA and FTA. An external vali-dation was performed using data from two different ethnic ICU populations (n = 30), resulting in acceptable bias and precision. Conclusion: The primary pharmacokinetic parameters obtained from critically ill Brazilian patients were similar to those observed in studies performed in critically ill patients of other ethnicities. Based on our results, the use of dose adjustment based on creati-nine clearance is required in Brazilian patients.

Bromazepam increases the error of the time interval judgments and modulates the EEG alpha asymmetry during time estimation.

AIM: This study investigated the bromazepam effects in male subjects during the time estimation performance and EEG alpha asymmetry in electrodes associated with the frontal and motor cortex. MATERIAL AND METHODS: This is a double-blind, crossover study with a sample of 32 healthy adults under control (placebo) vs. experimental (bromazepam) during visual time-estimation task in combination with electroencephalographic analysis. RESULTS: The results demonstrated that the bromazepam increased the relative error in the 4 s, 7 s, and 9 s intervals (p = 0.001). In addition, oral bromazepam modulated the EEG alpha asymmetry in cortical areas during the time judgment (p ≤ 0.025). CONCLUSION: The bromazepam decreases the precision of time estimation judgments and modulates the EEG alpha asymmetry, with greater left hemispheric dominance during time perception. Our findings suggest that bromazepam influences internal clock synchronization via the modulation of GABAergic receptors, strongly relating to attention, conscious perception, and behavioral performance.

Efficacy and safety of daily treatments for drug-susceptible pulmonary tuberculosis: a systematic review and network meta-analysis.

OBJECTIVES: To evaluate and update the evidence on the comparative efficacy and safety of antimicrobial drugs regimens for treating pulmonary drug-susceptible tuberculosis (DS-TB). METHODS: A systematic review was performed with searches in PubMed and Scopus (PROSPERO-CRD42019141463). We included randomised controlled trials comparing the effect of any antimicrobial regimen lasting at least 2 weeks. The outcomes of interest were culture conversion and incidence of adverse events. Bayesian network meta-analyses and surface under the cumulative ranking curve (SUCRA) analyses were performed. Results were reported as odds ratio with 95% credibility intervals. KEY FINDINGS: Fifteen studies were included the meta-analysis (n = 7560 patients). No regimen was statistically more effective than the WHO standard approach (rifampicin, isoniazid, ethambutol, and pyrazinamide). The use of rifapentine 450 mg instead of rifampicin in the standard regimen demonstrated to be statistically safer than all other options for serious adverse events (e.g. hepatotoxicity, arthralgia) (OR ranging from 0.0 [Crl 0.00-0.04] to 0.0 [0.00-0.97]; SUCRA probabilities of 10%). Therapies containing rifapentine (Rp1500HEZ, Rp900HEZ) and moxifloxacin (RMEZ, RHMZ) are effective regarding culture conversion, but statistical uncertainty on their safety profile exists. CONCLUSION: The WHO standard regimen remains an overall effective and safe alternative for DS-TB. For intensive phase treatments, drugs combinations with rifapentine and moxifloxacin seem to reduce treatment duration while maintaining efficacy.

Evaluation of the antifungal activity of α, ß, and δ-damascone and inclusion complexes in ß-cyclodextrin against Candida spp.

Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, ß, and δ-damascone and inclusion complexes with ß-cyclodextrin against different Candida spp. The inclusion complex of ß-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (ßDA-ßCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, ß, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. ß-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.

High-performance immune diagnosis of tuberculosis: Use of phage display and synthetic peptide in an optimized experimental design.

Immunoassays are practical and cost-effective approaches suitable for large-scale tuberculosis (TB) screening. This study identified new peptide mimotopes of Mycobacterium tuberculosis and applied them in the serodiagnosis of TB. Thereby, linear (X15, X8CX8) and constrained (LX-4 and LX-8) phage display peptide libraries were screened with purified Immunoglobulin G antibodies from TB-positive patients, and eight mimotopes were selected. The mimotope peptides were screened using the SPOT-synthesis technique followed by immunoblotting. Peptides P.Mt.PD.4 and P.Mt.PD.7 demonstrated the highest binding affinity and were chemically synthesized and used as antigens for enzyme-linked immunosorbent assay (ELISA) assays. Experimental designs were used to optimize the assays and to assess each variable's influence. Peptide P.Mt.PD.7 was differentiated between positive and negative samples and achieved 100% sensitivity and specificity when tested on a 100-sera panel. Therefore, the selected peptide was applied to the ELISA assay as a screening method for diagnosing TB represents a potential tool for helping to combat the disease.

Antinociceptive, anti-inflammatory and hypoglycemic activities of the ethanolic Turnera subulata Sm. flower extract in adult zebrafish (Danio rerio).

Turnera subulata Sm. belongs to the family Turneraceae and is found in Brazil. The present study evaluated the antinociceptive, anti-inflammatory, and hypoglycemic potential of T. subulata flower extract (EtFloTsu) in zebrafish (Danio rerio). The total phenol and flavonoid contents of EtFloTsu were determined and identified using the Folin Ciocalteu reagent and aluminum chloride (AlCl3), respectively. The constituents of the extract were identified by HPLC-DAD, and the in vitro antioxidant activity (DPPH) was determined, toxicity in brine shrimp, and acute toxicity of 96 h in adult zebrafish. In addition, adult zebrafish (n = 6/fish) were treated orally with EtFloTsu (4, 20, or 40 mg/kg; vo) and subjected to formalin-induced nociception tests (with its possible mechanism of action with camphor), carrageenan-induced inflammation, and D-glucose-induced hyperglycemia (111 mM). Oxidative stress in the liver and brain tissues was assessed. EtFloTsu showed high levels of phenolic and flavonoid compounds with antioxidant activity. The phytochemicals chlorogenic acid, luteolin-7-o-glucoside, vitexin, and apigenin-7-o-glucoside were also identified in EtFloTsu. The synergism between these constituents was possibly responsible for the antinociceptive (via TRPA1), anti-inflammatory, and hypoglycemic effects of EtFloTsu in adult zebrafish, without causing toxicity in animals. Therefore, T. subulata flowers have therapeutic agents that could treat pain, inflammation, diabetes, and related complications.Communicated by Ramaswamy H. Sarma.

Dioclea Altissima Seed Lectin (DAL) Prevents Anxiety-like Behavioral Responses in Adult Zebrafish (Danio Rerio): Involvement of GABAergic and 5-HT Systems.

BACKGROUND: Plant lectins have shown promising neuropharmacological activities in animal models. OBJECTIVE: This study evaluated the effect of Dioclea altissima seed lectin (DAL) on adult zebrafish behavior. METHOD: Zebrafish (n=6/group) were treated (i.p.; 20 µL) with DAL (0.025; 0.05 or 0.1 mg/mL), vehicle or diazepam (DZP) and submitted to several tests (open field, light/dark preference or novel tank). Flumazenil, pizotifen or granisetron were administered 15 min before DAL (0.05 mg/mL), and the animals were evaluated on light/dark preference test. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. RESULTS: DAL decreased the locomotor activity of adult zebrafish (0.025; 0.05 or 0.1 mg/mL), increased the time spent in the upper region of the aquarium (0.025 mg/mL), and decreased the latency time of adult zebrafish to enter the upper region on the novel tank test. DAL (0.05 mg/mL) also increased their permanence in the light zone of the light/dark preference test. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and was prevented by pizotifen, granizetron and flumazenil. CONCLUSION: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors.